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FDA approves talazoparib for metastatic prostate cancer
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Talazoparib is already approved for adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. The new approval, granted following priority review, is based on findings from the randomized, placebo-controlled, phase 3 TALAPRO-2 trial, published in The Lancet.
The 399 patients in the study were randomly assigned in a 1:1 ratio to receive either enzalutamide 160 mg daily plus either talazoparib 0.5 mg or placebo daily. Median radiographic progression-free survival (PFS) was not reached in the treatment group; it was 13.8 months in the placebo group (hazard ratio, 0.45). In an exploratory analysis by BRCA mutation status, patients with BRCA-mutated disease who received talazoparib exhibited an even stronger median radiographic PFS (HR, 0.20; not reached vs. 11 months) in comparison with those without BRCA-mutated disease (HR, 0.72; 24.7 vs. 16.7 months).
Serious adverse reactions occurred in 30% of patients who received talazoparib plus enzalutamide. The most common serious adverse reactions, reported in more than 2% of patients, included anemia (9%) and fracture (3%). Discontinuation of talazoparib occurred in 10% of patients, according to a Pfizer statement.
Pfizer also noted that a marketing authorization application for the drug combination has been accepted for review by the European Medicines Agency.
“Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy,” lead investigator Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, said in a statement. Patients with metastatic castration-resistant prostate cancer harboring HRR genetic alterations have even worse outcomes, and thus the FDA’s approval of the talazoparib and enzalutamide combination “represents a treatment option deserving of excitement and attention.”
A version of this article originally appeared on Medscape.com.
Huge underuse of germline testing for cancer patients
Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.
The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.
The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.
“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.
“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”
Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.
The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.
“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.
They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.
“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.
At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.
The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.
Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.
“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.
One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.
“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.
Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
Details of the study
Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.
It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.
She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”
However, “little is known about genetic testing use and results,” Dr. Kurian noted.
The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.
The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.
The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.
Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.
Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.
Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.
Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.
The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.
By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.
The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.
Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.
There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.
However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.
The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).
With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).
Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.
She also noted that the SEER registries do not collect data on family history or tumor sequencing.
The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.
The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.
The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.
“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.
“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”
Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.
The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.
“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.
They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.
“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.
At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.
The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.
Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.
“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.
One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.
“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.
Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
Details of the study
Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.
It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.
She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”
However, “little is known about genetic testing use and results,” Dr. Kurian noted.
The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.
The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.
The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.
Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.
Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.
Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.
Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.
The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.
By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.
The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.
Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.
There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.
However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.
The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).
With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).
Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.
She also noted that the SEER registries do not collect data on family history or tumor sequencing.
The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Information from germline genetic testing could affect a patient’s cancer care. For example, such testing could indicate that targeted therapies would be beneficial, and it would have implications for close relatives who may carry the same genes.
The finding that so few patients with newly diagnosed cancer were tested comes from an analysis of data on more than 1.3 million individuals across two U.S. states. The data were taken from the Surveillance, Epidemiology, and End Results (SEER) registry.
The rate is “well below guideline recommendations,” said study presenter Allison W. Kurian, MD, department of medicine, Stanford (Calif.) University.
“Innovative care delivery” is needed to tackle the problem, including the streamlining of pretest counseling, making posttest counseling more widely available, and employing long-term follow-up to track patient outcomes, she suggested.
“I do think this is a time for creative solutions of a number of different kinds,” she said. She suggested that lessons could be learned from the use of telemedicine during the COVID-19 pandemic. She also noted that “there have been some interesting studies on embedding genetic counselors in oncology clinics.”
Dr. Kurian presented the study at the annual meeting of the American Society of Clinical Oncology (ASCO). The study was simultaneously published in the Journal of the American Medical Association.
The current results represent a “missed opportunity for decrease the population-level burden of cancer,” experts noted in an accompanying editorial.
“Clinicians should recommend testing to their patients and provide them with the information necessary to make informed decisions about whether to undergo testing,” Zsofia K. Stadler, MD, and Deborah Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, New York, wrote in their editorial.
They suggested novel approaches to widen access, such as use of point-of-care testing, telecounseling, and, in the future, chatbots to respond to patient questions.
“With greater emphasis on overcoming both health system and patient-level barriers to genetic cancer susceptibility testing for patients with cancer, treatment outcomes will improve and cancer diagnoses and related deaths in family members will be prevented,” they concluded.
At the meeting, invited discussant Erin Frances Cobain, MD, assistant professor of medical oncology, University of Michigan Health, Ann Arbor, referring to breast cancer as an example, said that progress has “stagnated” in recent years.
The study found a higher rate of gene testing among patients with newly diagnosed breast cancer, at just over 20%.
Dr. Cobain argued that this was still too low. She pointed out that “a recent study suggested that over 60% of individuals with an incident cancer diagnosis would meet criteria for genetic testing by National Comprehensive Cancer Network guidelines.
“This may be because testing is not offered, there may be poor access to genetic counseling resources, or patients may be offered testing but decline it,” she suggested.
One compelling reason to conduct genetic testing for patients newly diagnosed with breast cancer is that it may show that they are candidates for treatment with PARP (poly[ADP]-ribose polymerase) inhibitors, which “may have a direct impact on cancer-related mortality,” she pointed out.
“We need increased awareness and access to genetic testing resources for patients with breast cancer, particularly for racial and ethnic minorities,” she said.
Dr. Cobain also noted that finding variants of uncertain significance (VUS) was more likely among patients from racial and ethnic minorities than among White patients. She said such a finding “increases patient and physician anxiety,” and there may be “unclear optimal management recommendations for these patients.”
Details of the study
Germline genetic testing is “increasingly essential for cancer care,” Dr. Kurian said.
It is central to risk-adapted screening and secondary prevention, the use of targeted therapies, including PARP and checkpoint inhibitors, and cascade testing to identify at-risk relatives.
She pointed out that in clinical practice, testing has “evolved rapidly.” Panels include more and more genes. In addition, the cost of these tests is falling, and guidelines have become “more expansive.”
However, “little is known about genetic testing use and results,” Dr. Kurian noted.
The team therefore undertook the SEER-GeneLINK initiative, which involved patients aged ≥ 20 years who were diagnosed with cancer between Jan. 1, 2013, and March 31, 2019, and who were reported to statewide SEER registries in California and Georgia.
The team looked for patients for whom germline genetic test results had been reported by the four laboratories that performed the majority of patient testing in the two states. Results were categorized as pathogenic, benign, or VUS.
The results were classified on the basis of current guidelines for testing and/or management as related to breast/ovarian cancer, gastrointestinal cancer, other hereditary cancers, or those with no guidelines for testing or management.
Dr. Kurian reported that from an overall population of 1,412,388 patients diagnosed with cancer, 1,369,660 were eligible for inclusion. Of those, about half (51.9%) were women, and the majority (86.3%) were aged 50 years or older.
Many of these patients (61.4%) were non-Hispanic White persons, and slightly fewer than half (49.8%) were deemed to be in medium or high poverty, as determined using U.S. Census tract levels.
Overall, germline genetic testing was performed in 93,052 (6.8%) of patients over the study period.
Women were more likely to have undergone germline mutation testing than men, at 13.9% vs. 2.2%, as were patients aged 20-49 years, at 22.1% vs. 8.2% for those aged 50-69 years, and 3.3% for those aged 70 years and older.
The number of genes for which testing was conducted increased from a median of 2 in 2013 to 34 in 2019. Rates of VUS increased more than that for pathologic variants and substantially more so in non-White patients.
By 2019, the ratio of VUS to pathologic variants stood at 1.7 among White patients, vs. 3.9 among Asian patients, 3.6 among Black patients, and 2.2 among Hispanic patients.
The majority of identified pathologic variants that were related to the diagnosed cancer and genes with testing and/or management guidelines accounted for 67.5% to 94.9% of such variants.
Regarding specific cancer diagnoses, Dr. Kurian said that over the course of the study period, testing rates consistently exceeded 50% only among male breast cancer patients.
There were rapid increases in testing for ovarian cancer, from 28.0% of cases in 2013 to 54.0% in 2019. For pancreatic cancer, rates increased from 1.0% to 19.0% over the same period, and for prostate cancer, rates increased from 0.1% to 4.0%. She suggested that these increases in rates may be related to the approval of PARP inhibitors for use in these indications.
However, there was little change in the rates of germline mutation testing for lung cancer patients, from 01% in 2013 to 0.8% in 2019, and for other cancers, from 0.3% to 2.0%.
The results also revealed racial and ethnic differences in testing after controlling for age, cancer type, and year. Over the course of the study period, 8.0% of White patients underwent genetic testing, compared with 6.0% each for Asian, Black, and Hispanic patients and 5.0% for other patients (P < .001).
With regard specifically to male and female breast cancer and ovarian cancer, testing rates were 31% among White patients, 22% for Asian patients, 25% for Black patients, and 23% for Hispanic patients (P < .001).
Dr. Kurian acknowledged that the study is limited by a lack of testing from other laboratories and direct-to-consumer test data, although a recent survey suggested that this represents fewer than 5% of all germline genetic tests.
She also noted that the SEER registries do not collect data on family history or tumor sequencing.
The study was funded by the National Institutes of Health, and the Centers for Disease Control and Prevention. Dr. Kurian has relationships with Adela, Ambry Genetics, Color Genomics, GeneDx/BioReference, Genentech, InVitae, and Myriad Genetics. Other authors report numerous relationships with industry. Dr. Cobain has ties with AstraZeneca, Daiichi Sankyo, Athenex, Ayala Pharmaceuticals, bioTheranostics, and Immunomedics. Dr. Schrag has relationships with Merck, JAMA, AACR, and Grail. Dr. Stadler has ties with Adverum Biotechnologies, Genentech, Neurogene, Novartis, Optos Plc, Outlook Therapeutics, and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
AT ASCO 2023
DEI training gives oncology fellows more confidence
The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).
Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.
“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”
Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.
The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).
At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.
First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.
Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.
Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.
“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”
Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.
The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.
The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.
Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.
Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.
“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”
No funding for the study was reported.
A version of this article first appeared on Medscape.com.
The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).
Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.
“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”
Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.
The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).
At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.
First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.
Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.
Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.
“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”
Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.
The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.
The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.
Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.
Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.
“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”
No funding for the study was reported.
A version of this article first appeared on Medscape.com.
The finding comes from a survey conducted after the introduction of DEI training within the Yale Medical Oncology-Hematology Fellowship Program. The study was reported by Norin Ansari, MD, MPH, of Yale Cancer Center, New Haven, Conn., at the annual meeting of the American Society of Clinical Oncology (ASCO).
Dr. Ansari emphasized the DEI curriculum in fellowship programs by highlighting the racial and gender disparities that exist among physicians.
“There is a significant representation problem – only 2%-3% of practicing oncologists are Black or Hispanic/Latino,” she said. “And that representation decreases with each stage in the pipeline of the workforce.”
Dr. Ansari also noted gender disparities in the oncologist workforce, reporting that about one-third of faculty positions are held by women.
The anonymous survey was sent to 29 fellows; 23 responded, including 8 first-year fellows and 13 senior fellows. Over 57% of respondents rated the importance of DEI education as 10 on a 10-point scale (mean, 8.6).
At the start of this year, the responses of senior fellows who had already received some DEI training during the previous year’s lecture series were compared with first-year fellows who had not had any fellowship DEI education.
First-year fellows reported a mean confidence score of 2.5/5 at navigating bias and microaggressions when experienced personally and a mean score of 2.9/5 when they were directed at others. Senior fellows reported mean confidence scores of 3 and 3.2, respectively.
Yale then compared longitudinal data on fellows’ comfort levels in navigating discrimination in 2021, 2022, and 2023 a month before the ASCO meeting.
Fellows were asked to rate their comfort level from 1 to 10 in navigating different types of discrimination, including racial inequality, sexual harassment, and gender discrimination. In these three categories, fellows rated comfortability as a 5 in 2021 and as 7 in 2023 after the DEI training.
“Our first goal is to normalize talking about DEI and to recognize that different people in our workforce have different experiences and how we can be allies for them and for our patients,” Dr. Ansari said. “And I think for long-term goals we want to take stock of who’s at the table, who’s making decisions, and how does that affect our field, our science, and our patients.”
Yale designed the 3-year longitudinal curriculum with two annual core topics: upstander training and journal club for discussion and reflection. An additional two to three training sessions per year will focus on either race, gender, LGBTQ+, disability, religion, or implicit bias training.
The most popular topics among fellows were upstander training, cancer treatment and outcomes disparities, recruitment and retention, and career promotion and pay disparities.
The preferred platforms of content delivery were lectures from experts in the field, affinity groups or mentorship links, small group discussions, and advocacy education.
Gerald Hsu, MD, PhD, with the San Francisco VA Medical Center, discussed the results of Yale’s DEI curriculum assessment, saying it represented “best practices” in the industry. However, he acknowledged that realistically, not everyone will be receptive to DEI training.
Dr. Hsu said that holding medical staff accountable is the only way to truly incorporate DEI into everyday practice.
“Collectively, we need to be holding ourselves to different standards or holding ourselves to some standard,” Dr. Hsu said. “Maybe we need to be setting goals to the degree to which we diversify our training programs and our faculty, and there needs to be consequences to not doing so.”
No funding for the study was reported.
A version of this article first appeared on Medscape.com.
FROM ASCO 2023
Drugmakers are abandoning cheap generics, and now U.S. cancer patients can’t get meds
On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.
Their decisions are likely to result in preventable deaths.
Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.
The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.
But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?
“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”
“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.
“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”
The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.
Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.
“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”
Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.
At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.
On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.
She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”
Doses remained at 80%, she said. Things hadn’t changed 10 days later.
Generics manufacturers are pulling out
The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.
As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.
The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.
Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.
The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.
Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.
Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”
Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.
“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
Should government step in?
Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.
As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.
Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”
More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.
“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.
Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.
In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.
“It would almost literally be a drop in the bucket.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.
Their decisions are likely to result in preventable deaths.
Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.
The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.
But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?
“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”
“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.
“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”
The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.
Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.
“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”
Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.
At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.
On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.
She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”
Doses remained at 80%, she said. Things hadn’t changed 10 days later.
Generics manufacturers are pulling out
The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.
As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.
The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.
Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.
The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.
Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.
Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”
Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.
“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
Should government step in?
Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.
As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.
Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”
More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.
“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.
Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.
In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.
“It would almost literally be a drop in the bucket.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
On Nov. 22, three Food and Drug Administration inspectors arrived at the sprawling Intas Pharmaceuticals plant south of Ahmedabad, India, and found hundreds of trash bags full of shredded documents tossed into a garbage truck. Over the next 10 days, the inspectors assessed what looked like a systematic effort to conceal quality problems at the plant, which provided more than half of the U.S. supply of generic cisplatin and carboplatin, two cheap drugs used to treat as many as 500,000 new cancer cases every year.
Their decisions are likely to result in preventable deaths.
Cisplatin and carboplatin are among scores of drugs in shortage, including 12 other cancer drugs, ADHD pills, blood thinners, and antibiotics. COVID-hangover supply chain issues and limited FDA oversight are part of the problem, but the main cause, experts agree, is the underlying weakness of the generic drug industry. Made mostly overseas, these old but crucial drugs are often sold at a loss or for little profit. Domestic manufacturers have little interest in making them, setting their sights instead on high-priced drugs with plump profit margins.
The problem isn’t new, and that’s particularly infuriating to many clinicians. President Joe Biden, whose son Beau died of an aggressive brain cancer, has focused his Cancer Moonshot on discovering cures – undoubtedly expensive ones. Indeed, existing brand-name cancer drugs often cost tens of thousands of dollars a year.
But what about the thousands of patients today who can’t get a drug like cisplatin, approved by the FDA in 1978 and costing as little as $6 a dose?
“It’s just insane,” said Mark Ratain, MD, a cancer doctor and pharmacologist at the University of Chicago. “Your roof is caving in, but you want to build a basketball court in the backyard because your wife is pregnant with twin boys and you want them to be NBA stars when they grow up?”
“It’s just a travesty that this is the level of health care in the United States of America right now,” said Stephen Divers, MD, an oncologist in Hot Springs, Ark., who in recent weeks has had to delay or change treatment for numerous bladder, breast, and ovarian cancer patients because his clinic cannot find enough cisplatin and carboplatin. Results from a survey of academic cancer centers released June 7 found 93% couldn’t find enough carboplatin and 70% had cisplatin shortages.
“All day, in between patients, we hold staff meetings trying to figure this out,” said Bonny Moore, MD, an oncologist in Fredericksburg, Virginia. “It’s the most nauseous I’ve ever felt. Our office stayed open during COVID; we never had to stop treating patients. We got them vaccinated, kept them safe, and now I can’t get them a $10 drug.”
The cancer clinicians KFF Health News interviewed for this story said that, given current shortages, they prioritize patients who can be cured over later-stage patients, in whom the drugs generally can only slow the disease, and for whom alternatives – though sometimes less effective and often with more side effects – are available. But some doctors are even rationing doses intended to cure.
Isabella McDonald, then a junior at Utah Valley University, was diagnosed in April with a rare, often fatal bone cancer, whose sole treatment for young adults includes the drug methotrexate. When Isabella’s second cycle of treatment began June 5, clinicians advised that she would be getting less than the full dose because of a methotrexate shortage, said her father, Brent.
“They don’t think it will have a negative impact on her treatment, but as far as I am aware, there isn’t any scientific basis to make that conclusion,” he said. “As you can imagine, when they gave us such low odds of her beating this cancer, it feels like we want to give it everything we can and not something short of the standard.”
Mr. McDonald stressed that he didn’t blame the staffers at Intermountain Health who take care of Isabella. The family – his other daughter, Cate, made a TikTok video about her sister’s plight – were simply stunned at such a basic flaw in the health care system.
At Dr. Moore’s practice, in Virginia, clinicians gave 60% of the optimal dose of carboplatin to some uterine cancer patients during the week of May 16, then shifted to 80% after a small shipment came in the following week. The doctors had to omit carboplatin from normal combination treatments for patients with recurrent disease, she said.
On June 2, Dr. Moore and colleagues were glued to their drug distributor’s website, anxious as teenagers waiting for Taylor Swift tickets to go on sale – only with mortal consequences at stake.
She later emailed KFF Health News: “Carboplatin did NOT come back in stock today. Neither did cisplatin.”
Doses remained at 80%, she said. Things hadn’t changed 10 days later.
Generics manufacturers are pulling out
The causes of shortages are well established. Everyone wants to pay less, and the middlemen who procure and distribute generics keep driving down wholesale prices. The average net price of generic drugs fell by more than half between 2016 and 2022, according to research by Anthony Sardella, a business professor at Washington University in St. Louis.
As generics manufacturers compete to win sales contracts with the big negotiators of such purchases, such as Vizient and Premier, their profits sink. Some are going out of business. Akorn, which made 75 common generics, went bankrupt and closed in February. Israeli generics giant Teva, which has a portfolio of 3,600 medicines, announced May 18 it was shifting to brand-name drugs and “high-value generics.” Lannett, with about 120 generics, announced a Chapter 11 reorganization amid declining revenue. Other companies are in trouble too, said David Gaugh, interim CEO of the Association for Accessible Medicines, the leading generics trade group.
The generics industry used to lose money on about a third of the drugs it produced, but now it’s more like half, Mr. Gaugh said. So when a company stops making a drug, others do not necessarily step up, he said. Officials at Fresenius Kabi and Pfizer said they have increased their carboplatin production since March, but not enough to end the shortage. On June 2, FDA Commissioner Robert Califf announced the agency had given emergency authorization for Chinese-made cisplatin to enter the U.S. market, but the impact of the move wasn’t immediately clear.
Cisplatin and carboplatin are made in special production lines under sterile conditions, and expanding or changing the lines requires FDA approval. Bargain-basement prices have pushed production overseas, where it’s harder for the FDA to track quality standards. The Intas plant inspection was a relative rarity in India, where the FDA in 2022 reportedly inspected only 3% of sites that make drugs for the U.S. market. Mr. Sardella testified in May that a quarter of all U.S. drug prescriptions are filled by companies that received FDA warning letters in the past 26 months. And pharmaceutical industry product recalls are at their highest level in 18 years, reflecting fragile supply conditions.
The FDA listed 137 drugs in shortage as of June 13, including many essential medicines made by few companies.
Intas voluntarily shut down its Ahmedabad plant after the FDA inspection, and the agency posted its shocking inspection report in January. Accord Healthcare, the U.S. subsidiary of Intas, said in mid-June it had no date for restarting production.
Asked why it waited 2 months after its inspection to announce the cisplatin shortage, given that Intas supplied more than half the U.S. market for the drug, the FDA said via email that it doesn’t list a drug in shortage until it has “confirmed that overall market demand is not being met.”
Prices for carboplatin, cisplatin, and other drugs have skyrocketed on the so-called gray market, where speculators sell medicines they snapped up in anticipation of shortages. A 600-mg bottle of carboplatin, normally available for $30, was going for $185 in early May and $345 a week later, said Richard Scanlon, the pharmacist at dr. Moore’s clinic.
“It’s hard to have these conversations with patients – ‘I have your dose for this cycle, but not sure about next cycle,’” said Mark Einstein, MD, chair of the department of obstetrics, gynecology and reproductive health at New Jersey Medical School, Newark.
Should government step in?
Despite a drug shortage task force and numerous congressional hearings, progress has been slow at best. The 2020 CARES Act gave the FDA the power to require companies to have contingency plans enabling them to respond to shortages, but the agency has not yet implemented guidance to enforce the provisions.
As a result, neither Accord nor other cisplatin makers had a response plan in place when Intas’ plant was shut down, said Soumi Saha, senior vice president of government affairs for Premier, which arranges wholesale drug purchases for more than 4,400 hospitals and health systems.
Premier understood in December that the shutdown endangered the U.S. supply of cisplatin and carboplatin, but it also didn’t issue an immediate alarm. “It’s a fine balance,” she said. “You don’t want to create panic-buying or hoarding.”
More lasting solutions are under discussion. Mr. Sardella and others have proposed government subsidies to get U.S. generics plants running full time. Their capacity is now half-idle. If federal agencies like the Centers for Medicare & Medicaid Services paid more for more safely and efficiently produced drugs, it would promote a more stable supply chain, he said.
“At a certain point the system needs to recognize there’s a high cost to low-cost drugs,” said Allan Coukell, senior vice president for public policy at Civica Rx, a nonprofit funded by health systems, foundations, and the federal government that provides about 80 drugs to hospitals in its network. Civica is building a $140 million factory near Petersburg, Va., that will produce dozens more, Mr. Coukell said.
Dr. Ratain and his University of Chicago colleague Satyajit Kosuri, MD, recently called for the creation of a strategic inventory buffer for generic medications, something like the Strategic Petroleum Reserve, set up in 1975 in response to the OPEC oil crisis.
In fact, Dr. Ratain reckons, selling a quarter-million barrels of oil would probably generate enough cash to make and store 2 years’ worth of carboplatin and cisplatin.
“It would almost literally be a drop in the bucket.”
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF – an independent source of health policy research, polling, and journalism. Learn more about KFF.
ACS officer provides ASCO highlights: Targeting hidden cancer, AI in oncology
And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.
Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.
Below are lightly edited excerpts from a conversation with Dr. Kamal:
Question: What are some of most groundbreaking studies released at ASCO?
Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.
For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).
Q: How do these findings add to current knowledge?
A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.
Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.
Q: What else struck you as especially important research?
A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.
This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.
Even in these smaller, early tumors, osimertinib makes a difference.
Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?
A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.
If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.
That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.
Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?
A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.
Q: How can AI be helpful to medical providers considering its limitations?
A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.
Q: Will AI threaten the careers of oncologists?
A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.
Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.
Dr. Kamal has no disclosures.
And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.
Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.
Below are lightly edited excerpts from a conversation with Dr. Kamal:
Question: What are some of most groundbreaking studies released at ASCO?
Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.
For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).
Q: How do these findings add to current knowledge?
A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.
Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.
Q: What else struck you as especially important research?
A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.
This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.
Even in these smaller, early tumors, osimertinib makes a difference.
Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?
A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.
If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.
That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.
Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?
A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.
Q: How can AI be helpful to medical providers considering its limitations?
A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.
Q: Will AI threaten the careers of oncologists?
A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.
Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.
Dr. Kamal has no disclosures.
And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.
Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.
Below are lightly edited excerpts from a conversation with Dr. Kamal:
Question: What are some of most groundbreaking studies released at ASCO?
Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.
For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).
Q: How do these findings add to current knowledge?
A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.
Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.
Q: What else struck you as especially important research?
A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.
This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.
Even in these smaller, early tumors, osimertinib makes a difference.
Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?
A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.
If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.
That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.
Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?
A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.
Q: How can AI be helpful to medical providers considering its limitations?
A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.
Q: Will AI threaten the careers of oncologists?
A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.
Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.
Dr. Kamal has no disclosures.
AT ASCO 2023
Widespread carboplatin, cisplatin shortages: NCCN survey
The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.
“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.
“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”
The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.
“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.
Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.
The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.
The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.
“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”
In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:
- “Current shipments from established manufacturers have been paused.”
- “The supply of carboplatin available is not meeting our demands.”
- “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”
Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”
Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.
The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.
The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”
Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”
A version of this article first appeared on Medscape.com.
The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.
“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.
“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”
The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.
“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.
Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.
The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.
The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.
“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”
In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:
- “Current shipments from established manufacturers have been paused.”
- “The supply of carboplatin available is not meeting our demands.”
- “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”
Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”
Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.
The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.
The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”
Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”
A version of this article first appeared on Medscape.com.
The survey, which included responses from 27 NCCN member institutions, revealed that 93% are experiencing a shortage of carboplatin and that 70% have reported a shortage of cisplatin.
“This is an unacceptable situation,” Robert W. Carlson, MD, NCCN’s chief executive offer, said in the statement released by the network.
“We are hearing from oncologists and pharmacists across the country who have to scramble to find appropriate alternatives for treating their patients with cancer right now,” Dr. Carlson said. And while the survey results show patients are still able to get lifesaving care, “it comes at a burden to our overtaxed medical facilities.”
The NCCN called on the federal government, the pharmaceutical industry, providers, and payers to take steps to “help mitigate any impacts” from this cancer drug shortage.
“We need to work together to improve the current situation and prevent it from happening again in the future,” Dr. Carlson stressed.
Carboplatin and cisplatin, which are frequently used together for systemic treatment, are highly effective therapies prescribed to treat many cancer types, including lung, breast, and prostate cancers, as well as leukemias and lymphomas. An estimated 500,000 new patients with cancer receive these agents each year.
The current survey, conducted over the last week of May, found that 100% of responding centers are able to continue to treat patients who need cisplatin without delays.
The same cannot be said for carboplatin: only 64% of centers said they are still able to continue treating all current patients receiving the platinum-based therapy. Among 19 responding centers, 20% reported that they were continuing carboplatin regimens for some but not all patients. And 16% reported treatment delays from having to obtain prior authorization for modified treatment plans, though none reported denials.
“Carboplatin has been in short supply for months but in the last 4 weeks has reached a critical stage,” according to one survey comment. “Without additional inventory many of our sites will be out of drug by early next week.”
In response to the survey question, “Is your center experiencing a shortage of carboplatin,” others made similar comments:
- “Current shipments from established manufacturers have been paused.”
- “The supply of carboplatin available is not meeting our demands.”
- “Without additional supply in early June, we will have to implement several shortage mitigation strategies.”
Survey respondents also addressed whether manufacturers or suppliers have provided any indication of when these drugs will become readily available again. For both drugs, about 60% of respondents said no. And for those who do receive updates, many noted that the “information is tentative and variable.”
Respondents indicated that other cancer agents, including methotrexate (67%) and 5FU (26%), are also in short supply at their centers.
The shortage and the uncertainty as to when it will end are forcing some centers to develop conservation and mitigation strategies.
The NCCN has broadly outlined how the federal government, the pharmaceutical industry, providers, and payers can help with prevention and mitigation. The NCCN has called on the federal government and the pharmaceutical industry to work to secure a steady supply of core anticancer drugs and has asked payers to “put patients first and provide flexible and efficient systems of providing coverage for alternative therapies replacing anti-cancer drugs that are unavailable or in shortage.”
Overall, the survey results “demonstrate the widespread impact of the chemotherapy shortage,” said Alyssa Schatz, MSW, senior director of policy and advocacy for NCCN. “We hope that by sharing this survey and calling for united action across the oncology community, we can come together to prevent future drug shortages and ensure quality, effective, equitable, and accessible cancer care for all.”
A version of this article first appeared on Medscape.com.
Risk of falls seen with newer antiandrogens for prostate cancer
Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.
However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.
the authors reported.
These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.
The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.
The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.
Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.
The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.
The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.
The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
Study details
The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.
The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).
Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).
The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).
The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.
Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.
The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.
The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.
A version of this article first appeared on Medscape.com.
Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.
However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.
the authors reported.
These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.
The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.
The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.
Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.
The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.
The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.
The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
Study details
The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.
The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).
Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).
The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).
The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.
Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.
The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.
The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.
A version of this article first appeared on Medscape.com.
Second-generation antiandrogens (AAs) – abiraterone, apalutamide, darolutamide, and enzalutamide – are a cornerstone of modern prostate cancer treatment, improving outcomes and survival.
However, they carry a significant caveat, according to a new meta-analysis of 12 clinical trials with over 13,000 patients.
the authors reported.
These findings carry “important public health indications” because use of second-generation AAs, currently first-line treatment for advanced and castration-resistant prostate cancer, is expanding with new indications, meaning that the pool of men at risk for such problems is large and growing, the team wrote.
The take-home message is that the findings give men – and the physicians who counsel them – a fuller idea of what to expect when considering using the agents, the researchers comment. This information is key at a time when so much of prostate cancer treatment involves carefully weighing the risks and benefits, they added.
The study was published in JAMA Oncology. It was conducted by a team of researchers from the University of Texas MD Anderson Cancer Center, Houston, and was led by Malgorzata Nowakowska, a medical student at Baylor College of Medicine, Houston.
Two prostate cancer specialists agreed and gave an example to bring the point home in an accompanying editorial.
The risk-benefit ratio of adding a second-generation AA to treatment may be different for a patient who wants to stay alert and sharp to keep a complex job “versus someone whose primary goal is to see their young children graduate high school,” Alexandra Sokolova, MD, of the Oregon Health and Science University, Portland, and Julie Graff, MD, of the VA Portland (Ore.) Health Care System, wrote in their editorial.
The study fills a “critical gap” when it comes to counseling men about the drugs and will help guide discussions, they said.
The investigators said their study also highlights the need for additional research to identify who is most at risk for the side effects and the best way to prevent and treat them. “Interventions currently under investigation include donepezil, methylphenidate, low-fat diet, acupuncture, martial arts, and high-intensity exercise, among many others,” Ms. Nowakowska and colleagues noted.
Study details
The 12 trials in the meta-analysis, which compared second-generation AAs with placebo, were conducted from 2008 to 2021. These trials were multinational investigations that included patients with metastatic disease as well as those with nonmetastatic disease. The median age across the studies ranged from 67 to 74 years, and trial follow-up ranged from 3.9 to 48 months.
The rates of adverse cognitive effects and attention disorders and disturbances ranged from 2% to 8% among patients who received second-generation AAs versus 2%-3% among those who received placebo, a more than doubling of the risk of cognitive toxic effects (P = .002).
Fatigue of any grade was reported in 5%-45% of participants taking second-generation AAs versus 2%-42% of patients taking placebos, which translates to a 34% higher risk (P < .001).
The use of AAs was associated with an 87% increase in the risk of falls in comparison with placebo, regardless of severity. For falls of grade 3 or higher that required hospitalization or invasive treatment, the increase in risk with second-generation AAs was 72% (P = .05).
The findings were consistent for cognitive toxicity and fatigue in studies that included traditional hormone therapy in both the treatment and control arms. Increased age was associated with a greater risk of fatigue.
Study limits include the fact that it was not known how long patients were taking the drugs before they encountered problems. In addition, the findings were not broken down with respect to medication, so it’s unknown whether such problems are worse with some second-generation AAs than with others.
The editorialists noted that real-world patients tend to be older and sicker than patients in trials, so the risk of falls, fatigue, and cognition problems might be higher among everyday patients.
The study was funded by the National Institutes of Health and others. The investigators disclosed no relevant financial relationships. Dr. Sokolova has received personal fees from Lantheus and travel grants from AstraZeneca. Dr. Graff has received nonfinancial support from Janssen, Pfizer/Astellas, and Sanofi.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Posluma approved for PET imaging in prostate cancer
The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.
Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.
Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.
Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”
However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
Approval based on two single-arm trials
Posluma’s approval was based on two single-arm trials from Blue Earth.
In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.
Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.
“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.
The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.
Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.
Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.
Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).
The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.
The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”
In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”
The labeling for gozetotide carries the same warnings and precautions.
A version of this article first appeared on Medscape.com.
The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.
Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.
Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.
Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”
However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
Approval based on two single-arm trials
Posluma’s approval was based on two single-arm trials from Blue Earth.
In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.
Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.
“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.
The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.
Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.
Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.
Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).
The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.
The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”
In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”
The labeling for gozetotide carries the same warnings and precautions.
A version of this article first appeared on Medscape.com.
The product is approved for use in men with suspected metastasis who are candidates for definitive therapy and for men with suspected recurrence, as evidenced by elevations in serum prostate-specific antigen (PSA) level, according to a press release from marketer Blue Earth Diagnostics.
Posluma binds prostate-specific membrane antigen (PSMA), which is usually overexpressed on prostate cancer cells, and tags the cells with fluorine-18 (F18), a positron emitter. Because of the radiolabeling, PET imaging can be used to gauge the extent of disease.
Posluma will be available in the United States in June 2023 from Blue Earth’s U.S. manufacturer and distributor, PETNET Solutions.
Blue Earth says that its new agent, which was known as 18F-rhPSMA-7.3 PET during trials, “is the first and only FDA-approved, PSMA-targeted imaging agent developed with proprietary radiohybrid technology.”
However, a similar product is currently on the U.S. market – the PSMA PET imaging radiopharmaceutical gallium-68 gozetotide (Illuccix, Locometz), which has the same two indications. Gozetotide is also indicated for metastatic prostate cancer amenable to lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy.
Approval based on two single-arm trials
Posluma’s approval was based on two single-arm trials from Blue Earth.
In the LIGHTHOUSE trial, 296 men underwent Posluma PET imaging before radical prostatectomy with pelvic lymph node dissection. About a quarter turned out to have positive nodes on pathology.
Posluma’s sensitivity for predicting positive nodes was low, ranging from 23% to 30% among three readers who were blinded to clinical information, but its specificity was high, ranging from 93% to 97%, according to the product labeling.
“The study showed that Posluma PET provided clinically valuable information prior to surgery that would likely result in management changes for these patients,” said investigator Brian Chapin, MD, a urologist at the University of Texas MD Anderson Cancer Center, Houston, in the company press release.
The second trial, SPOTLIGHT, included 389 men suspected of experiencing recurrence on the basis of elevations in PSA.
Posluma PET’s ability to detect true recurrence was compared with use of histology or other imaging techniques, including CT, MRI, technetium-99m bone scan, and fluciclovine F18 PET. In regions deemed positive for recurrence on Posluma PET by three readers, 46%-60% were positive by the other techniques, the labeling says.
Overall, the “results demonstrated high detection rates ... even at low PSA levels,” Blue Earth said.
Adverse events were minimal in the trials. The most frequent were diarrhea (0.7%), increases in blood pressure (0.5%), and injection-site pain (0.4%).
The product labeling warns that Posluma PET contributes to patients’ overall long-term cumulative radiation exposure and that interpretation with respect to recurrence may differ among readers.
The labeling also cautions that “a negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. ... Uptake is not specific for prostate cancer and may occur in other types of cancer, in nonmalignant processes, and in normal tissues.”
In addition, it notes that androgen deprivation therapy “and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of flotufolastat F18 in prostate cancer.”
The labeling for gozetotide carries the same warnings and precautions.
A version of this article first appeared on Medscape.com.
Urology groups endorse two prostate biopsy approaches
CHICAGO - , endorsing both transperineal and transrectal biopsy instead of choosing one over the other.
The new guidelines, issued at the annual meeting of the American Urological Association, contrast with 2021 recommendations from the European Association of Urologists (EAU), which regard the transperineal approach as superior to and safer than the transrectal approach.
The new guidelines state: “Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C).” Grade C is the lowest grade of acceptance the guideline committee could issue, according to Daniel Lin, MD, vice-chair of the AUA guideline panel.
“The AUA looked at all the higher-level data comparing the two procedures. There was a lack of that data,” Dr. Lin, chief of urologic oncology at the University of Washington, Seattle, said in an interview. He said the literature consists mainly of systematic single-center reviews, rather than multicenter randomized trials.
But Hendrik Van Poppel, MD, policy chief for the EAU, said that in Europe, transrectal biopsies are now considered “medical malpractice.”
Philip Cornford, MD, associate professor of urology at the University of Liverpool, England, and chair of the prostate biopsy guidelines panel for the EAU, said the society in 2021 concluded that the transperineal approach is the preferred one.
The EAU stated that transperineal prostate biopsies should be performed “due to the lower risk of infectious complications.” The EAU described the evidence as strong: A meta-analysis of seven studies that included 1,330 patients showed that for patients undergoing transperineal biopsy, infectious complications were significantly reduced.
Dr. Cornford said in essence, the EAU made its decision out of concern about infections, whereas the AUA and SUO based their decision on the ability of the methods to detect cancer.
Advocates for transperineal procedures cite several studies that show that the rate of infection, including sepsis, with such biopsies is virtually zero.
However, Dr. Lin noted that the committee said existing data on infection did not support this position. He also cited a “a fairly compelling” single-center randomized study with 750 patients that showed no difference in infection rates. The study was presented at the AUA meeting.
Agents of death and destruction?
Badar Mian, MD, professor of surgery at Albany (N.Y.) Medical College, who led the study, told an AUA session that urology has been trapped in an “echo chamber” regarding the relative safety of biopsies.
Clinicians hear “loud proclamations, which get repeated and magnified, that there is a real zero risk of complications after transperineal biopsies as compared to the horrendous 5% to 10% or higher rate of transrectal biopsy complications and that you, with your transrectal biopsies, are the cause of death and destruction all around,” Dr. Mian said. “Well, if you step out of the echo chamber, what you’ll find is that the accurate complications amongst the two procedures are not that dramatically different, much less dramatic than what you’ve been told to believe.”
The campaign to end transrectal biopsies in Europe started in 2018 with the death of a Norwegian man who experienced an infection after the procedure. Truls Bjerklund Johansen, MD, who’d performed the biopsy on the patient and who worked with the man’s daughter to change national practice, persuaded the EAU to look at the issue.
Advocates also say transperineal biopsies are better at detecting anterior and apical cancers.
“I would agree the data on cancer detection is less convincing, but that is not the basis of the EAU recommendation,” Dr. Cornford said.
Arvin George, MD, leads the transperineal biopsy program at the University of Michigan, Ann Arbor, and directs the transperineal training program at the AUA’s annual meeting. He said his course was sold out early and included about 60 trainees.
Dr. George said the new guideline statement “is not an unequivocal endorsement for transperineal biopsy as the preferred approach for diagnostic sampling but rather an acknowledgment of this approach as an alternative option.”
He said that although the new position statement should increase awareness of the transperineal approach in the United States, “without a strong recommendation, the guideline statement is unlikely to spark a large switch to the transperineal biopsy but rather supports the continued slow and steady adoption.”
Matthew Allaway, DO, founder of Perineologic, developer of the PrecisionPoint Transperineal Access System, said industry figures show that about 10% of the 1.5 million prostate biopsies performed in the United States annually are performed transperineally, a doubling in 2 years.
Jeremy Grummet, MD, clinical professor of urology at Monash University, Melbourne, and leader of the TREXIT (Transperineal Exit) movement to abandon transrectal procedures, said the AUA guidelines are biased toward “physician convenience.”
Lack of training
The AUA said another reason it did not endorse the transperineal approach was that currently, American urologists lack training and experience with transperineal procedures.
Dr. Grummet blamed major medical centers for any gap in the familiarity of clinicians with transperineal biopsies, which have been available for more than a decade.
“It is incumbent on the leaders of urology departments globally to ensure that their colleagues are trained in transperineal biopsy and have access to the appropriate equipment,” he said in an interview. “Lack of training didn’t seem to prevent the rapid uptake of robotic prostatectomy – a far more complex procedure.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO - , endorsing both transperineal and transrectal biopsy instead of choosing one over the other.
The new guidelines, issued at the annual meeting of the American Urological Association, contrast with 2021 recommendations from the European Association of Urologists (EAU), which regard the transperineal approach as superior to and safer than the transrectal approach.
The new guidelines state: “Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C).” Grade C is the lowest grade of acceptance the guideline committee could issue, according to Daniel Lin, MD, vice-chair of the AUA guideline panel.
“The AUA looked at all the higher-level data comparing the two procedures. There was a lack of that data,” Dr. Lin, chief of urologic oncology at the University of Washington, Seattle, said in an interview. He said the literature consists mainly of systematic single-center reviews, rather than multicenter randomized trials.
But Hendrik Van Poppel, MD, policy chief for the EAU, said that in Europe, transrectal biopsies are now considered “medical malpractice.”
Philip Cornford, MD, associate professor of urology at the University of Liverpool, England, and chair of the prostate biopsy guidelines panel for the EAU, said the society in 2021 concluded that the transperineal approach is the preferred one.
The EAU stated that transperineal prostate biopsies should be performed “due to the lower risk of infectious complications.” The EAU described the evidence as strong: A meta-analysis of seven studies that included 1,330 patients showed that for patients undergoing transperineal biopsy, infectious complications were significantly reduced.
Dr. Cornford said in essence, the EAU made its decision out of concern about infections, whereas the AUA and SUO based their decision on the ability of the methods to detect cancer.
Advocates for transperineal procedures cite several studies that show that the rate of infection, including sepsis, with such biopsies is virtually zero.
However, Dr. Lin noted that the committee said existing data on infection did not support this position. He also cited a “a fairly compelling” single-center randomized study with 750 patients that showed no difference in infection rates. The study was presented at the AUA meeting.
Agents of death and destruction?
Badar Mian, MD, professor of surgery at Albany (N.Y.) Medical College, who led the study, told an AUA session that urology has been trapped in an “echo chamber” regarding the relative safety of biopsies.
Clinicians hear “loud proclamations, which get repeated and magnified, that there is a real zero risk of complications after transperineal biopsies as compared to the horrendous 5% to 10% or higher rate of transrectal biopsy complications and that you, with your transrectal biopsies, are the cause of death and destruction all around,” Dr. Mian said. “Well, if you step out of the echo chamber, what you’ll find is that the accurate complications amongst the two procedures are not that dramatically different, much less dramatic than what you’ve been told to believe.”
The campaign to end transrectal biopsies in Europe started in 2018 with the death of a Norwegian man who experienced an infection after the procedure. Truls Bjerklund Johansen, MD, who’d performed the biopsy on the patient and who worked with the man’s daughter to change national practice, persuaded the EAU to look at the issue.
Advocates also say transperineal biopsies are better at detecting anterior and apical cancers.
“I would agree the data on cancer detection is less convincing, but that is not the basis of the EAU recommendation,” Dr. Cornford said.
Arvin George, MD, leads the transperineal biopsy program at the University of Michigan, Ann Arbor, and directs the transperineal training program at the AUA’s annual meeting. He said his course was sold out early and included about 60 trainees.
Dr. George said the new guideline statement “is not an unequivocal endorsement for transperineal biopsy as the preferred approach for diagnostic sampling but rather an acknowledgment of this approach as an alternative option.”
He said that although the new position statement should increase awareness of the transperineal approach in the United States, “without a strong recommendation, the guideline statement is unlikely to spark a large switch to the transperineal biopsy but rather supports the continued slow and steady adoption.”
Matthew Allaway, DO, founder of Perineologic, developer of the PrecisionPoint Transperineal Access System, said industry figures show that about 10% of the 1.5 million prostate biopsies performed in the United States annually are performed transperineally, a doubling in 2 years.
Jeremy Grummet, MD, clinical professor of urology at Monash University, Melbourne, and leader of the TREXIT (Transperineal Exit) movement to abandon transrectal procedures, said the AUA guidelines are biased toward “physician convenience.”
Lack of training
The AUA said another reason it did not endorse the transperineal approach was that currently, American urologists lack training and experience with transperineal procedures.
Dr. Grummet blamed major medical centers for any gap in the familiarity of clinicians with transperineal biopsies, which have been available for more than a decade.
“It is incumbent on the leaders of urology departments globally to ensure that their colleagues are trained in transperineal biopsy and have access to the appropriate equipment,” he said in an interview. “Lack of training didn’t seem to prevent the rapid uptake of robotic prostatectomy – a far more complex procedure.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO - , endorsing both transperineal and transrectal biopsy instead of choosing one over the other.
The new guidelines, issued at the annual meeting of the American Urological Association, contrast with 2021 recommendations from the European Association of Urologists (EAU), which regard the transperineal approach as superior to and safer than the transrectal approach.
The new guidelines state: “Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C).” Grade C is the lowest grade of acceptance the guideline committee could issue, according to Daniel Lin, MD, vice-chair of the AUA guideline panel.
“The AUA looked at all the higher-level data comparing the two procedures. There was a lack of that data,” Dr. Lin, chief of urologic oncology at the University of Washington, Seattle, said in an interview. He said the literature consists mainly of systematic single-center reviews, rather than multicenter randomized trials.
But Hendrik Van Poppel, MD, policy chief for the EAU, said that in Europe, transrectal biopsies are now considered “medical malpractice.”
Philip Cornford, MD, associate professor of urology at the University of Liverpool, England, and chair of the prostate biopsy guidelines panel for the EAU, said the society in 2021 concluded that the transperineal approach is the preferred one.
The EAU stated that transperineal prostate biopsies should be performed “due to the lower risk of infectious complications.” The EAU described the evidence as strong: A meta-analysis of seven studies that included 1,330 patients showed that for patients undergoing transperineal biopsy, infectious complications were significantly reduced.
Dr. Cornford said in essence, the EAU made its decision out of concern about infections, whereas the AUA and SUO based their decision on the ability of the methods to detect cancer.
Advocates for transperineal procedures cite several studies that show that the rate of infection, including sepsis, with such biopsies is virtually zero.
However, Dr. Lin noted that the committee said existing data on infection did not support this position. He also cited a “a fairly compelling” single-center randomized study with 750 patients that showed no difference in infection rates. The study was presented at the AUA meeting.
Agents of death and destruction?
Badar Mian, MD, professor of surgery at Albany (N.Y.) Medical College, who led the study, told an AUA session that urology has been trapped in an “echo chamber” regarding the relative safety of biopsies.
Clinicians hear “loud proclamations, which get repeated and magnified, that there is a real zero risk of complications after transperineal biopsies as compared to the horrendous 5% to 10% or higher rate of transrectal biopsy complications and that you, with your transrectal biopsies, are the cause of death and destruction all around,” Dr. Mian said. “Well, if you step out of the echo chamber, what you’ll find is that the accurate complications amongst the two procedures are not that dramatically different, much less dramatic than what you’ve been told to believe.”
The campaign to end transrectal biopsies in Europe started in 2018 with the death of a Norwegian man who experienced an infection after the procedure. Truls Bjerklund Johansen, MD, who’d performed the biopsy on the patient and who worked with the man’s daughter to change national practice, persuaded the EAU to look at the issue.
Advocates also say transperineal biopsies are better at detecting anterior and apical cancers.
“I would agree the data on cancer detection is less convincing, but that is not the basis of the EAU recommendation,” Dr. Cornford said.
Arvin George, MD, leads the transperineal biopsy program at the University of Michigan, Ann Arbor, and directs the transperineal training program at the AUA’s annual meeting. He said his course was sold out early and included about 60 trainees.
Dr. George said the new guideline statement “is not an unequivocal endorsement for transperineal biopsy as the preferred approach for diagnostic sampling but rather an acknowledgment of this approach as an alternative option.”
He said that although the new position statement should increase awareness of the transperineal approach in the United States, “without a strong recommendation, the guideline statement is unlikely to spark a large switch to the transperineal biopsy but rather supports the continued slow and steady adoption.”
Matthew Allaway, DO, founder of Perineologic, developer of the PrecisionPoint Transperineal Access System, said industry figures show that about 10% of the 1.5 million prostate biopsies performed in the United States annually are performed transperineally, a doubling in 2 years.
Jeremy Grummet, MD, clinical professor of urology at Monash University, Melbourne, and leader of the TREXIT (Transperineal Exit) movement to abandon transrectal procedures, said the AUA guidelines are biased toward “physician convenience.”
Lack of training
The AUA said another reason it did not endorse the transperineal approach was that currently, American urologists lack training and experience with transperineal procedures.
Dr. Grummet blamed major medical centers for any gap in the familiarity of clinicians with transperineal biopsies, which have been available for more than a decade.
“It is incumbent on the leaders of urology departments globally to ensure that their colleagues are trained in transperineal biopsy and have access to the appropriate equipment,” he said in an interview. “Lack of training didn’t seem to prevent the rapid uptake of robotic prostatectomy – a far more complex procedure.”
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT AUA 2023
Limit PSA screening to men with symptoms
A new strategy proposed by an international team of experts would limit the use of the prostate-specific antigen (PSA) test for screening tor prostate cancer to men who are younger than 70 years and who are at high risk or symptomatic.
This would reduce potential harms from overdiagnosis and overtreatment, the risk for which is high with the on-demand screening that is the current standard of care in most wealthy nations.
In a paper published online in The BMJ, the panel recommends instead a comprehensive nationwide program that would base PSA testing on individual patient risk and direct those with abnormal results to a managed system of imaging, targeted biopsy only if indicated, and subsequent active monitoring or treatment for those with more aggressive disease features.
Alternatively, government health programs could actively discourage widespread PSA testing and implement policies that would effectively limit PSA-based screening only to men with urologic symptoms warranting further exploration, said the authors, led by Andrew Vickers, PhD, a research epidemiologist at Memorial Sloan Kettering Cancer Center in New York.
“Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity,” they wrote.
“To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns,” they continued.
Inappropriate testing
Since the Food and Drug Administration approved the first PSA screen in 1986 as a means for monitoring disease progression in patients being treated for prostate cancer, the test has remained controversial, embraced by some for its presumed ability to spot early prostate cancer but scorned by others for its equivocal results in patients with benign prostate pathology and for its potential to lead to overdiagnosis and overtreatment of low-grade disease in men who would otherwise be likely to die of other causes.
Currently, only Lithuania and Kazakhstan have government-supported population-based screening programs for prostate cancer. In contrast, the United States, United Kingdom, and other high-income countries have opted not to implement nationwide prostate cancer screening but allow so-called “informed choice testing,” in which men can receiving PSA screening after discussion with a primary care physician, urologist, or other specialist.
The U.S. Preventive Services Task Force recommends that for men aged 55-69 years, the decision to undergo PSA testing should be an individual one, based on an understanding of the risks and benefits. For men aged 70 or older, the task force flatly states, “Do not screen for prostate cancer.”
But as Dr. Vickers and colleagues noted, “high income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution.”
For example, they pointed out that in the United Kingdom, men in their 80s are twice as likely as are men in their 50s to get a PSA test, even though men in the older age group are far less likely to have benefit and far more likely to experience harm from treatment. Similarly, in France, nearly one-third of men over 40 get an annual PSA test, with the highest incidence of PSA testing in men over age 70. There are also high rates of PSA testing in men over 70 in Italy, Germany, and Ireland.
“A key problem is that, in current routine care – and despite guidelines to the contrary – most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer,” Dr. Vickers and colleagues wrote. “Furthermore, most men with biopsy-detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low-risk tumors that are unlikely to cause cancer related morbidity or mortality.”
In addition, informed-choice PSA testing may lead to health inequities, the team noted, citing data from the United States, Canada, and Switzerland showing an inverse association between income and education and the likelihood of PSA testing. Also, in the United States and Canada, men from ethnic minority groups are less likely to have PSA testing.
Comprehensive risk-based program
Dr. Vickers and colleagues proposed that a “comprehensive, risk-based prostate cancer detection program based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment.
“Such a program would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging [MRI] or blood markers), and limit treatment to those with high Gleason grade tumors,” they wrote.
‘Sound analysis’
Two experts who were not involved with the BMJ paper applaud the suggestions made in comments posted on the U.K. Science Media Centre.
Benjamin W. Lamb, MBBS, MA, PhD, a consultant urologist and surgeon at Barts Health NHS Trust in London, said the analysis conducted by the panel “is sound as there are known benefits from risk-adapted comprehensive screening trials in men aged 50-70, but discordance with current practice, meaning benefits and harms are not those seen in trials.”
However, he also said that the strategies proposed by the authors would be unlikely to prevent older, well-informed men from requesting and getting a PSA test.
“In my view, the emphasis should be on engaging younger and at-risk men rather than restricting access for older men,” he said, noting that the alternative proposal of restricting PSA testing “in my view, is not feasible.”
Nick James, MBBS, PhD, professor of prostate and bladder cancer research at the Institute of Cancer Research, London, and consultant oncologist at the Royal Marsden NHS Foundation Trust, said, “I agree with the authors and strongly support the implementation of a risk-based approach to PSA testing at a national level.
“There is an urgent need for a more equitable and targeted screening strategy, which could help address existing health disparities,” Dr. James said. “Currently, individuals from economically disadvantaged backgrounds are less likely to undergo PSA testing. Men in their 50s or younger, who may stand to benefit more from these tests, are also less likely to receive PSA tests compared to older men who benefit less. Linked to better diagnostic pathways with MRI, already standard in the UK, potential harms from overdiagnosis and overtreatment can be mitigated.”
The analysis was supported in part by the U.S. National Institutes of Health/National Cancer Institute with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center, and NIH grants to coauthors. Dr. Vickers is a coinventor of the 4Kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test and owns stock options in OPKO, which offers the test. Coauthor James W.F. Catto, PhD, disclosed ties to Astellas, AstraZeneca, BMS, Ferring, Gilead, Janssen, MSD, Nucleix, Photocure, QED Therapeutics, and Roche.
A version of this article first appeared on Medscape.com.
A new strategy proposed by an international team of experts would limit the use of the prostate-specific antigen (PSA) test for screening tor prostate cancer to men who are younger than 70 years and who are at high risk or symptomatic.
This would reduce potential harms from overdiagnosis and overtreatment, the risk for which is high with the on-demand screening that is the current standard of care in most wealthy nations.
In a paper published online in The BMJ, the panel recommends instead a comprehensive nationwide program that would base PSA testing on individual patient risk and direct those with abnormal results to a managed system of imaging, targeted biopsy only if indicated, and subsequent active monitoring or treatment for those with more aggressive disease features.
Alternatively, government health programs could actively discourage widespread PSA testing and implement policies that would effectively limit PSA-based screening only to men with urologic symptoms warranting further exploration, said the authors, led by Andrew Vickers, PhD, a research epidemiologist at Memorial Sloan Kettering Cancer Center in New York.
“Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity,” they wrote.
“To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns,” they continued.
Inappropriate testing
Since the Food and Drug Administration approved the first PSA screen in 1986 as a means for monitoring disease progression in patients being treated for prostate cancer, the test has remained controversial, embraced by some for its presumed ability to spot early prostate cancer but scorned by others for its equivocal results in patients with benign prostate pathology and for its potential to lead to overdiagnosis and overtreatment of low-grade disease in men who would otherwise be likely to die of other causes.
Currently, only Lithuania and Kazakhstan have government-supported population-based screening programs for prostate cancer. In contrast, the United States, United Kingdom, and other high-income countries have opted not to implement nationwide prostate cancer screening but allow so-called “informed choice testing,” in which men can receiving PSA screening after discussion with a primary care physician, urologist, or other specialist.
The U.S. Preventive Services Task Force recommends that for men aged 55-69 years, the decision to undergo PSA testing should be an individual one, based on an understanding of the risks and benefits. For men aged 70 or older, the task force flatly states, “Do not screen for prostate cancer.”
But as Dr. Vickers and colleagues noted, “high income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution.”
For example, they pointed out that in the United Kingdom, men in their 80s are twice as likely as are men in their 50s to get a PSA test, even though men in the older age group are far less likely to have benefit and far more likely to experience harm from treatment. Similarly, in France, nearly one-third of men over 40 get an annual PSA test, with the highest incidence of PSA testing in men over age 70. There are also high rates of PSA testing in men over 70 in Italy, Germany, and Ireland.
“A key problem is that, in current routine care – and despite guidelines to the contrary – most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer,” Dr. Vickers and colleagues wrote. “Furthermore, most men with biopsy-detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low-risk tumors that are unlikely to cause cancer related morbidity or mortality.”
In addition, informed-choice PSA testing may lead to health inequities, the team noted, citing data from the United States, Canada, and Switzerland showing an inverse association between income and education and the likelihood of PSA testing. Also, in the United States and Canada, men from ethnic minority groups are less likely to have PSA testing.
Comprehensive risk-based program
Dr. Vickers and colleagues proposed that a “comprehensive, risk-based prostate cancer detection program based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment.
“Such a program would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging [MRI] or blood markers), and limit treatment to those with high Gleason grade tumors,” they wrote.
‘Sound analysis’
Two experts who were not involved with the BMJ paper applaud the suggestions made in comments posted on the U.K. Science Media Centre.
Benjamin W. Lamb, MBBS, MA, PhD, a consultant urologist and surgeon at Barts Health NHS Trust in London, said the analysis conducted by the panel “is sound as there are known benefits from risk-adapted comprehensive screening trials in men aged 50-70, but discordance with current practice, meaning benefits and harms are not those seen in trials.”
However, he also said that the strategies proposed by the authors would be unlikely to prevent older, well-informed men from requesting and getting a PSA test.
“In my view, the emphasis should be on engaging younger and at-risk men rather than restricting access for older men,” he said, noting that the alternative proposal of restricting PSA testing “in my view, is not feasible.”
Nick James, MBBS, PhD, professor of prostate and bladder cancer research at the Institute of Cancer Research, London, and consultant oncologist at the Royal Marsden NHS Foundation Trust, said, “I agree with the authors and strongly support the implementation of a risk-based approach to PSA testing at a national level.
“There is an urgent need for a more equitable and targeted screening strategy, which could help address existing health disparities,” Dr. James said. “Currently, individuals from economically disadvantaged backgrounds are less likely to undergo PSA testing. Men in their 50s or younger, who may stand to benefit more from these tests, are also less likely to receive PSA tests compared to older men who benefit less. Linked to better diagnostic pathways with MRI, already standard in the UK, potential harms from overdiagnosis and overtreatment can be mitigated.”
The analysis was supported in part by the U.S. National Institutes of Health/National Cancer Institute with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center, and NIH grants to coauthors. Dr. Vickers is a coinventor of the 4Kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test and owns stock options in OPKO, which offers the test. Coauthor James W.F. Catto, PhD, disclosed ties to Astellas, AstraZeneca, BMS, Ferring, Gilead, Janssen, MSD, Nucleix, Photocure, QED Therapeutics, and Roche.
A version of this article first appeared on Medscape.com.
A new strategy proposed by an international team of experts would limit the use of the prostate-specific antigen (PSA) test for screening tor prostate cancer to men who are younger than 70 years and who are at high risk or symptomatic.
This would reduce potential harms from overdiagnosis and overtreatment, the risk for which is high with the on-demand screening that is the current standard of care in most wealthy nations.
In a paper published online in The BMJ, the panel recommends instead a comprehensive nationwide program that would base PSA testing on individual patient risk and direct those with abnormal results to a managed system of imaging, targeted biopsy only if indicated, and subsequent active monitoring or treatment for those with more aggressive disease features.
Alternatively, government health programs could actively discourage widespread PSA testing and implement policies that would effectively limit PSA-based screening only to men with urologic symptoms warranting further exploration, said the authors, led by Andrew Vickers, PhD, a research epidemiologist at Memorial Sloan Kettering Cancer Center in New York.
“Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity,” they wrote.
“To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns,” they continued.
Inappropriate testing
Since the Food and Drug Administration approved the first PSA screen in 1986 as a means for monitoring disease progression in patients being treated for prostate cancer, the test has remained controversial, embraced by some for its presumed ability to spot early prostate cancer but scorned by others for its equivocal results in patients with benign prostate pathology and for its potential to lead to overdiagnosis and overtreatment of low-grade disease in men who would otherwise be likely to die of other causes.
Currently, only Lithuania and Kazakhstan have government-supported population-based screening programs for prostate cancer. In contrast, the United States, United Kingdom, and other high-income countries have opted not to implement nationwide prostate cancer screening but allow so-called “informed choice testing,” in which men can receiving PSA screening after discussion with a primary care physician, urologist, or other specialist.
The U.S. Preventive Services Task Force recommends that for men aged 55-69 years, the decision to undergo PSA testing should be an individual one, based on an understanding of the risks and benefits. For men aged 70 or older, the task force flatly states, “Do not screen for prostate cancer.”
But as Dr. Vickers and colleagues noted, “high income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution.”
For example, they pointed out that in the United Kingdom, men in their 80s are twice as likely as are men in their 50s to get a PSA test, even though men in the older age group are far less likely to have benefit and far more likely to experience harm from treatment. Similarly, in France, nearly one-third of men over 40 get an annual PSA test, with the highest incidence of PSA testing in men over age 70. There are also high rates of PSA testing in men over 70 in Italy, Germany, and Ireland.
“A key problem is that, in current routine care – and despite guidelines to the contrary – most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer,” Dr. Vickers and colleagues wrote. “Furthermore, most men with biopsy-detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low-risk tumors that are unlikely to cause cancer related morbidity or mortality.”
In addition, informed-choice PSA testing may lead to health inequities, the team noted, citing data from the United States, Canada, and Switzerland showing an inverse association between income and education and the likelihood of PSA testing. Also, in the United States and Canada, men from ethnic minority groups are less likely to have PSA testing.
Comprehensive risk-based program
Dr. Vickers and colleagues proposed that a “comprehensive, risk-based prostate cancer detection program based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment.
“Such a program would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging [MRI] or blood markers), and limit treatment to those with high Gleason grade tumors,” they wrote.
‘Sound analysis’
Two experts who were not involved with the BMJ paper applaud the suggestions made in comments posted on the U.K. Science Media Centre.
Benjamin W. Lamb, MBBS, MA, PhD, a consultant urologist and surgeon at Barts Health NHS Trust in London, said the analysis conducted by the panel “is sound as there are known benefits from risk-adapted comprehensive screening trials in men aged 50-70, but discordance with current practice, meaning benefits and harms are not those seen in trials.”
However, he also said that the strategies proposed by the authors would be unlikely to prevent older, well-informed men from requesting and getting a PSA test.
“In my view, the emphasis should be on engaging younger and at-risk men rather than restricting access for older men,” he said, noting that the alternative proposal of restricting PSA testing “in my view, is not feasible.”
Nick James, MBBS, PhD, professor of prostate and bladder cancer research at the Institute of Cancer Research, London, and consultant oncologist at the Royal Marsden NHS Foundation Trust, said, “I agree with the authors and strongly support the implementation of a risk-based approach to PSA testing at a national level.
“There is an urgent need for a more equitable and targeted screening strategy, which could help address existing health disparities,” Dr. James said. “Currently, individuals from economically disadvantaged backgrounds are less likely to undergo PSA testing. Men in their 50s or younger, who may stand to benefit more from these tests, are also less likely to receive PSA tests compared to older men who benefit less. Linked to better diagnostic pathways with MRI, already standard in the UK, potential harms from overdiagnosis and overtreatment can be mitigated.”
The analysis was supported in part by the U.S. National Institutes of Health/National Cancer Institute with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center, and NIH grants to coauthors. Dr. Vickers is a coinventor of the 4Kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test and owns stock options in OPKO, which offers the test. Coauthor James W.F. Catto, PhD, disclosed ties to Astellas, AstraZeneca, BMS, Ferring, Gilead, Janssen, MSD, Nucleix, Photocure, QED Therapeutics, and Roche.
A version of this article first appeared on Medscape.com.