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Liquid biopsy–based test detects BRAF mutations
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
Analysis of plasma-derived cell-free DNA can identify BRAF mutations as accurately as formalin-fixed paraffin-embedded tumor sample analysis, investigators report.
Of 160 patients with advanced solid tumors, BRAF V600 mutations were detected in 62 (39%) archival formalin-fixed paraffin-embedded (FFPE) tumor samples and 47 (29%) plasma cell-free (cf) DNA samples. The two methods had overall agreement in 141 patients (88%; kappa coefficient, 0.74; SE, 0.06; 95% confidence interval, 0.63-0.85), Dr. Filip Janku of the University of Texas and his associates reported (Mol Cancer Ther. 2016 May 20. doi: 10.1158/1535-7163.MCT-15-0712).
BRAF mutations are prevalent in many types of advanced cancers, and targeting these mutations has demonstrated efficacy, but current assessment of BRAF mutations is limited by a lack of tissue samples and complicated by constantly changing mutation status.
cfDNA is secreted into the circulation by tumor cells and cells in the tumor microenvironment that are undergoing apoptosis or necroptosis and might serve as an alternate source for determining BRAF mutation.
“Collecting plasma cfDNA is a minimally invasive procedure that can be repeated at multiple times for diagnostic and disease-monitoring purposes,” Dr. Janku and associates said.
The investigators analyzed plasma samples from 160 patients with advanced solid tumors – most commonly colorectal cancer and melanoma –who had available archival FFPE tumor samples. cfDNA was isolated and extracted from whole blood and analyzed using the Idylla BRAF Mutation Test, a fully integrated real-time polymerase chain reaction–based test with a turnaround time of about 90 minutes.
Dr. Janku and associates found that a higher amount of mutant cfDNA was associated with shorter overall survival. Mean overall survival for patients with a BRAF-mutant cfDNA percentage of less than 2% (10.7 months; 95% CI, 9-12.4) was significantly longer than patients with a BRAF-mutant cfDNA percentage of greater than 2% (4.4 months; 95% CI, 3.2-5.6). Similar results were observed using different percentage cutoffs.
“Our study shows that the Idylla system can detect BRAF V600 mutations in plasma-derived cfDNA from patients with advanced cancers and has acceptable concordance (baseline, 88%; any time point, 90%); sensitivity (baseline, 73%; any time, 77%); and specificity (baseline, 98%; any time, 98%), compared with CLIA-certified laboratory testing of FFPE tumor tissue obtained at different times during routine care,” investigators wrote.
This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
On Twitter @JessCraig_OP
FROM MOLECULAR CANCER THERAPEUTICS
Key clinical point: Analysis of plasma-derived cfDNA can identify BRAF mutations as accurately as FFPE tumor sample analysis.
Major finding: Concordance between mutation analysis of FFPE tumor samples and plasma cfDNA was in overall agreement (88%; kappa, 0.74; SE, 0.06; 95% CI, 0.63-0.85).
Data source: Analysis of FFPE tumor samples and plasma-derived cfDNA for 160 patients with advanced cancers.
Disclosures: This study was supported by Biocartis, the Elsa U. Pardee Foundation, and the Sidney Kimmel Foundation for Cancer Research. Five of the investigators reported serving in an advisory role for, having ownership interest in, or receiving financial compensation or honoraria from multiple companies. The other investigators reported having no disclosures.
‘Extreme’ monitoring fails to boost survival in breast cancer patients
Extreme users of disease-monitoring tests do not have significantly improved overall survival, investigators reported.
A review of Surveillance, Epidemiology, and End Results (SEER) Medicare data on 2,460 women older than 65 years of age with advanced breast cancer revealed that 924 patients (37.6%) were extreme users of disease-monitoring tests, defined as having had more than 12 serum-tumor marker (STM) tests and/or more than four radiographic imaging tests in a 1-year time period.
“The objectives of this study were to identify patterns and predictors of use and extreme use of disease-monitoring tests among women with [metastatic breast cancer],” reported Dr. Melissa Accordino of Columbia University, New York, and her colleagues (JCO. 2016 May 9. [doi: 10.1200/JCO.2016.66.6313]).
The investigators reviewed SEER Medicare data on women with pathologically confirmed metastatic breast cancer diagnosed from 2002 to 2011. Costs of care were calculated from Medicare reimbursement claims from physician, hospital, outpatient, durable medical equipment, and hospice filings from the date of diagnosis through the date of death or the end of the study period. Per-patient-per-year serum tumor marker testing rate and per-patient-per-year radiographic imaging rates were calculated.
Of the 2,460-person cohort, 37.6% were classified as extreme users (9% were extreme users of STM and 32.8% were extreme users of radiographic imaging tests), Dr. Accordino and her associates reported.
There was no difference in overall survival between extreme users and the rest of the cohort (HR, 0.93; 95% CI, 0.86-1.02).
A multivariate model showed that women who were older than 80 years (OR, 0.58; 95% CI, 0.45-0.75) and patients who were single (OR, 0.77; 95% CI, 0.63-0.93) were less likely to be extreme users while patients who had more frequent oncology-related doctor’s visits were more likely to be extreme users (OR, 3.14; 95% CI, 2.49-3.96).
A linear regression model revealed that costs of care were significantly higher for patients categorized as extreme users whose mean annual cost of care was 50.6% (95% CI, 40.7-61.1) higher than the mean cost of care for those who weren’t extreme users (P less than .001).
“In addition to cost, frequent disease monitoring can be associated with emotional harm. The prevalence of anxiety and depression among patients with advanced cancers is estimated to be 25%-65%. Previous work has shown that depression and anxiety can increase over time in patients with metastatic solid tumors and has been attributed to multiple factors, including fear of death and fear of disease progression. … In a study that assessed distress in women during the surveillance period, women with more frequent testing had higher levels of anxiety without survival benefit,” the investigators wrote.
The investigators also discussed the potential conflict of interest for physicians who benefit financially from disease-monitoring tests. “A successful strategy may be to change policy for reimbursement,” they wrote.
“In addition, better evidence is needed with regard to the benefits and harms of frequent disease-monitoring testing to inform guidelines,” the investigators wrote. “Future research should determine the most cost-effective strategy to monitor patients with [metastatic breast cancer].”
This study was supported by fellowships and grants from the National Cancer Institute, the ASCO/Breast Cancer Research Foundation, and the Conquer Cancer Foundation. Dr. Accordino reported having no disclosures. One investigator reported having a consulting/advisory role with Pfizer, TEVA Pharmaceutical Industries, Otsuka, United Biosource, and EHE International.
On Twitter@JessCraig_OP
“I agree in general with the results and conclusions from this manuscript. It makes sense,” said Dr. Charles Loprinzi, Regis Professor of Breast Cancer Research at the Mayo Clinic, in an interview. “More tests do not necessarily mean more benefit. More frequent testing may help to determine early progression of disease, and then this may lead to earlier treatment changes.”
“There is a spectrum of clinicians who are more frequent testers versus infrequent testers,” Dr. Loprinzi explained. “I am on the side of not getting a lot of tests, as sometimes they provide too much information. For example, if I have a patient with metastatic breast cancer and a lump that I can feel on her chest wall or a pathologically palpable lymph node and also had a couple lung nodules, I would tend to follow this patient primarily by history and physical examination. Other physicians might order imaging tests every 3 months. I am less likely to order frequent imaging tests as long as the patient is feeling well and has responded to their anticancer therapy as per repeat physical examinations,” he said.
Shirley Mertz, president of the Metastatic Breast Cancer Network, a national, independent, nonprofit all-volunteer patient advocacy group, took issue with the generalized conclusions investigators drew. “The title of the article and the paragraph describing [the] purpose of the article infer that the authors studied the community of women living with metastatic breast cancer,” Ms. Mertz said in an interview.
“In reality, the authors looked at data from a very small proportion of women living with metastatic breast cancer – those who received a de novo diagnosis and were 65 and older. The authors then drew a broad conclusion about all elderly women based on their selected small proportion of patients. … How can the authors accurately state, ‘One-third of all elderly patients are extreme users of disease-monitoring tests?’ ”
“The selection by the authors of the word ‘extreme users’ is curious,” Ms. Mertz continued. “ ‘Extreme’ has a negative connotation and implies someone is doing something to excess. So, are readers expected to draw the conclusions of the authors? Did the authors consider a less emotional term such as ‘frequent’ or ‘heavy?’ Or does their choice of extreme help support the conclusions that ‘women with metastatic breast cancer are driving up health care costs?’ ”
When asked about the definition of extreme users, Dr. Loprinzi said, “I don’t think that there is a clinical definition of an extreme user. The authors came up with an innovative study idea and thus had to define an endpoint, which I think it is quite reasonable.”
Ms. Mertz also pointed out that while the investigators reported demographics of the study population, there was no analysis of the demographic of the medical oncologists who wrote the orders for disease-monitoring tests. “Such information is important and could be informative of issues underlying heavy use of diagnostic tests,” Ms. Mertz suggested.
Dr. Loprinzi agreed. “Is the frequent testing doctor driven or patient driven, or are they both? I suspect they are both,” he said. “That would be an interesting topic for an investigator to explore. Potentially, records could demonstrate a pattern for individual practitioners.”
What about the authors’ assertion that frequent testing is associated with emotional harm? “For some patients for whom STMs [serum tumor markers] do reflect their relative burden of metastasis, the STMs in conjunction with imaging can offer some measure of reassurance that a particular treatment is working,” Ms. Mertz said.
“What is needed is more research to develop blood markers that can be used with imaging with confidence in the clinic to monitor metastatic disease and response to treatment. We need to add to or improve upon the oncologists’ diagnostic tools, not curb their use as the authors suggest,” she added.
Dr. Loprinzi and Ms. Mertz made these comments during interviews.
“I agree in general with the results and conclusions from this manuscript. It makes sense,” said Dr. Charles Loprinzi, Regis Professor of Breast Cancer Research at the Mayo Clinic, in an interview. “More tests do not necessarily mean more benefit. More frequent testing may help to determine early progression of disease, and then this may lead to earlier treatment changes.”
“There is a spectrum of clinicians who are more frequent testers versus infrequent testers,” Dr. Loprinzi explained. “I am on the side of not getting a lot of tests, as sometimes they provide too much information. For example, if I have a patient with metastatic breast cancer and a lump that I can feel on her chest wall or a pathologically palpable lymph node and also had a couple lung nodules, I would tend to follow this patient primarily by history and physical examination. Other physicians might order imaging tests every 3 months. I am less likely to order frequent imaging tests as long as the patient is feeling well and has responded to their anticancer therapy as per repeat physical examinations,” he said.
Shirley Mertz, president of the Metastatic Breast Cancer Network, a national, independent, nonprofit all-volunteer patient advocacy group, took issue with the generalized conclusions investigators drew. “The title of the article and the paragraph describing [the] purpose of the article infer that the authors studied the community of women living with metastatic breast cancer,” Ms. Mertz said in an interview.
“In reality, the authors looked at data from a very small proportion of women living with metastatic breast cancer – those who received a de novo diagnosis and were 65 and older. The authors then drew a broad conclusion about all elderly women based on their selected small proportion of patients. … How can the authors accurately state, ‘One-third of all elderly patients are extreme users of disease-monitoring tests?’ ”
“The selection by the authors of the word ‘extreme users’ is curious,” Ms. Mertz continued. “ ‘Extreme’ has a negative connotation and implies someone is doing something to excess. So, are readers expected to draw the conclusions of the authors? Did the authors consider a less emotional term such as ‘frequent’ or ‘heavy?’ Or does their choice of extreme help support the conclusions that ‘women with metastatic breast cancer are driving up health care costs?’ ”
When asked about the definition of extreme users, Dr. Loprinzi said, “I don’t think that there is a clinical definition of an extreme user. The authors came up with an innovative study idea and thus had to define an endpoint, which I think it is quite reasonable.”
Ms. Mertz also pointed out that while the investigators reported demographics of the study population, there was no analysis of the demographic of the medical oncologists who wrote the orders for disease-monitoring tests. “Such information is important and could be informative of issues underlying heavy use of diagnostic tests,” Ms. Mertz suggested.
Dr. Loprinzi agreed. “Is the frequent testing doctor driven or patient driven, or are they both? I suspect they are both,” he said. “That would be an interesting topic for an investigator to explore. Potentially, records could demonstrate a pattern for individual practitioners.”
What about the authors’ assertion that frequent testing is associated with emotional harm? “For some patients for whom STMs [serum tumor markers] do reflect their relative burden of metastasis, the STMs in conjunction with imaging can offer some measure of reassurance that a particular treatment is working,” Ms. Mertz said.
“What is needed is more research to develop blood markers that can be used with imaging with confidence in the clinic to monitor metastatic disease and response to treatment. We need to add to or improve upon the oncologists’ diagnostic tools, not curb their use as the authors suggest,” she added.
Dr. Loprinzi and Ms. Mertz made these comments during interviews.
“I agree in general with the results and conclusions from this manuscript. It makes sense,” said Dr. Charles Loprinzi, Regis Professor of Breast Cancer Research at the Mayo Clinic, in an interview. “More tests do not necessarily mean more benefit. More frequent testing may help to determine early progression of disease, and then this may lead to earlier treatment changes.”
“There is a spectrum of clinicians who are more frequent testers versus infrequent testers,” Dr. Loprinzi explained. “I am on the side of not getting a lot of tests, as sometimes they provide too much information. For example, if I have a patient with metastatic breast cancer and a lump that I can feel on her chest wall or a pathologically palpable lymph node and also had a couple lung nodules, I would tend to follow this patient primarily by history and physical examination. Other physicians might order imaging tests every 3 months. I am less likely to order frequent imaging tests as long as the patient is feeling well and has responded to their anticancer therapy as per repeat physical examinations,” he said.
Shirley Mertz, president of the Metastatic Breast Cancer Network, a national, independent, nonprofit all-volunteer patient advocacy group, took issue with the generalized conclusions investigators drew. “The title of the article and the paragraph describing [the] purpose of the article infer that the authors studied the community of women living with metastatic breast cancer,” Ms. Mertz said in an interview.
“In reality, the authors looked at data from a very small proportion of women living with metastatic breast cancer – those who received a de novo diagnosis and were 65 and older. The authors then drew a broad conclusion about all elderly women based on their selected small proportion of patients. … How can the authors accurately state, ‘One-third of all elderly patients are extreme users of disease-monitoring tests?’ ”
“The selection by the authors of the word ‘extreme users’ is curious,” Ms. Mertz continued. “ ‘Extreme’ has a negative connotation and implies someone is doing something to excess. So, are readers expected to draw the conclusions of the authors? Did the authors consider a less emotional term such as ‘frequent’ or ‘heavy?’ Or does their choice of extreme help support the conclusions that ‘women with metastatic breast cancer are driving up health care costs?’ ”
When asked about the definition of extreme users, Dr. Loprinzi said, “I don’t think that there is a clinical definition of an extreme user. The authors came up with an innovative study idea and thus had to define an endpoint, which I think it is quite reasonable.”
Ms. Mertz also pointed out that while the investigators reported demographics of the study population, there was no analysis of the demographic of the medical oncologists who wrote the orders for disease-monitoring tests. “Such information is important and could be informative of issues underlying heavy use of diagnostic tests,” Ms. Mertz suggested.
Dr. Loprinzi agreed. “Is the frequent testing doctor driven or patient driven, or are they both? I suspect they are both,” he said. “That would be an interesting topic for an investigator to explore. Potentially, records could demonstrate a pattern for individual practitioners.”
What about the authors’ assertion that frequent testing is associated with emotional harm? “For some patients for whom STMs [serum tumor markers] do reflect their relative burden of metastasis, the STMs in conjunction with imaging can offer some measure of reassurance that a particular treatment is working,” Ms. Mertz said.
“What is needed is more research to develop blood markers that can be used with imaging with confidence in the clinic to monitor metastatic disease and response to treatment. We need to add to or improve upon the oncologists’ diagnostic tools, not curb their use as the authors suggest,” she added.
Dr. Loprinzi and Ms. Mertz made these comments during interviews.
Extreme users of disease-monitoring tests do not have significantly improved overall survival, investigators reported.
A review of Surveillance, Epidemiology, and End Results (SEER) Medicare data on 2,460 women older than 65 years of age with advanced breast cancer revealed that 924 patients (37.6%) were extreme users of disease-monitoring tests, defined as having had more than 12 serum-tumor marker (STM) tests and/or more than four radiographic imaging tests in a 1-year time period.
“The objectives of this study were to identify patterns and predictors of use and extreme use of disease-monitoring tests among women with [metastatic breast cancer],” reported Dr. Melissa Accordino of Columbia University, New York, and her colleagues (JCO. 2016 May 9. [doi: 10.1200/JCO.2016.66.6313]).
The investigators reviewed SEER Medicare data on women with pathologically confirmed metastatic breast cancer diagnosed from 2002 to 2011. Costs of care were calculated from Medicare reimbursement claims from physician, hospital, outpatient, durable medical equipment, and hospice filings from the date of diagnosis through the date of death or the end of the study period. Per-patient-per-year serum tumor marker testing rate and per-patient-per-year radiographic imaging rates were calculated.
Of the 2,460-person cohort, 37.6% were classified as extreme users (9% were extreme users of STM and 32.8% were extreme users of radiographic imaging tests), Dr. Accordino and her associates reported.
There was no difference in overall survival between extreme users and the rest of the cohort (HR, 0.93; 95% CI, 0.86-1.02).
A multivariate model showed that women who were older than 80 years (OR, 0.58; 95% CI, 0.45-0.75) and patients who were single (OR, 0.77; 95% CI, 0.63-0.93) were less likely to be extreme users while patients who had more frequent oncology-related doctor’s visits were more likely to be extreme users (OR, 3.14; 95% CI, 2.49-3.96).
A linear regression model revealed that costs of care were significantly higher for patients categorized as extreme users whose mean annual cost of care was 50.6% (95% CI, 40.7-61.1) higher than the mean cost of care for those who weren’t extreme users (P less than .001).
“In addition to cost, frequent disease monitoring can be associated with emotional harm. The prevalence of anxiety and depression among patients with advanced cancers is estimated to be 25%-65%. Previous work has shown that depression and anxiety can increase over time in patients with metastatic solid tumors and has been attributed to multiple factors, including fear of death and fear of disease progression. … In a study that assessed distress in women during the surveillance period, women with more frequent testing had higher levels of anxiety without survival benefit,” the investigators wrote.
The investigators also discussed the potential conflict of interest for physicians who benefit financially from disease-monitoring tests. “A successful strategy may be to change policy for reimbursement,” they wrote.
“In addition, better evidence is needed with regard to the benefits and harms of frequent disease-monitoring testing to inform guidelines,” the investigators wrote. “Future research should determine the most cost-effective strategy to monitor patients with [metastatic breast cancer].”
This study was supported by fellowships and grants from the National Cancer Institute, the ASCO/Breast Cancer Research Foundation, and the Conquer Cancer Foundation. Dr. Accordino reported having no disclosures. One investigator reported having a consulting/advisory role with Pfizer, TEVA Pharmaceutical Industries, Otsuka, United Biosource, and EHE International.
On Twitter@JessCraig_OP
Extreme users of disease-monitoring tests do not have significantly improved overall survival, investigators reported.
A review of Surveillance, Epidemiology, and End Results (SEER) Medicare data on 2,460 women older than 65 years of age with advanced breast cancer revealed that 924 patients (37.6%) were extreme users of disease-monitoring tests, defined as having had more than 12 serum-tumor marker (STM) tests and/or more than four radiographic imaging tests in a 1-year time period.
“The objectives of this study were to identify patterns and predictors of use and extreme use of disease-monitoring tests among women with [metastatic breast cancer],” reported Dr. Melissa Accordino of Columbia University, New York, and her colleagues (JCO. 2016 May 9. [doi: 10.1200/JCO.2016.66.6313]).
The investigators reviewed SEER Medicare data on women with pathologically confirmed metastatic breast cancer diagnosed from 2002 to 2011. Costs of care were calculated from Medicare reimbursement claims from physician, hospital, outpatient, durable medical equipment, and hospice filings from the date of diagnosis through the date of death or the end of the study period. Per-patient-per-year serum tumor marker testing rate and per-patient-per-year radiographic imaging rates were calculated.
Of the 2,460-person cohort, 37.6% were classified as extreme users (9% were extreme users of STM and 32.8% were extreme users of radiographic imaging tests), Dr. Accordino and her associates reported.
There was no difference in overall survival between extreme users and the rest of the cohort (HR, 0.93; 95% CI, 0.86-1.02).
A multivariate model showed that women who were older than 80 years (OR, 0.58; 95% CI, 0.45-0.75) and patients who were single (OR, 0.77; 95% CI, 0.63-0.93) were less likely to be extreme users while patients who had more frequent oncology-related doctor’s visits were more likely to be extreme users (OR, 3.14; 95% CI, 2.49-3.96).
A linear regression model revealed that costs of care were significantly higher for patients categorized as extreme users whose mean annual cost of care was 50.6% (95% CI, 40.7-61.1) higher than the mean cost of care for those who weren’t extreme users (P less than .001).
“In addition to cost, frequent disease monitoring can be associated with emotional harm. The prevalence of anxiety and depression among patients with advanced cancers is estimated to be 25%-65%. Previous work has shown that depression and anxiety can increase over time in patients with metastatic solid tumors and has been attributed to multiple factors, including fear of death and fear of disease progression. … In a study that assessed distress in women during the surveillance period, women with more frequent testing had higher levels of anxiety without survival benefit,” the investigators wrote.
The investigators also discussed the potential conflict of interest for physicians who benefit financially from disease-monitoring tests. “A successful strategy may be to change policy for reimbursement,” they wrote.
“In addition, better evidence is needed with regard to the benefits and harms of frequent disease-monitoring testing to inform guidelines,” the investigators wrote. “Future research should determine the most cost-effective strategy to monitor patients with [metastatic breast cancer].”
This study was supported by fellowships and grants from the National Cancer Institute, the ASCO/Breast Cancer Research Foundation, and the Conquer Cancer Foundation. Dr. Accordino reported having no disclosures. One investigator reported having a consulting/advisory role with Pfizer, TEVA Pharmaceutical Industries, Otsuka, United Biosource, and EHE International.
On Twitter@JessCraig_OP
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Extreme use of disease-monitoring tests significantly elevates health care costs and provides no survival benefit.
Major finding: Costs of care were significantly higher for patients categorized as extreme users whose mean annual cost of care was 50.6% (95% CI, 40.7-61.1) higher than the mean cost of care for those who weren’t extreme users (P less than .001). There was also no difference in overall survival between extreme users and the rest of the cohort (HR, 0.93; 95% CI, 0.86-1.02).
Data source: A retrospective study of SEER Medicare data on 2,460 women with breast cancer.
Disclosures: This study was supported by fellowships and grants from the National Cancer Institute, the ASCO/Breast Cancer Research Foundation, and the Conquer Cancer Foundation. Dr. Accordino reported having no disclosures. One investigator reported having a consulting/advisory role with Pfizer, TEVA Pharmeceutical Industries, Otsuka, United Biosource, and EHE International.
Adrenal gland tumors linked to ADHD diagnosis
Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.
In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.
PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.
ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.
In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).
“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.
“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.
Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.
Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).
Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.
Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.
“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.
“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.
The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.
On Twitter @JessCraig_OP
Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.
In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.
PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.
ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.
In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).
“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.
“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.
Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.
Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).
Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.
Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.
“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.
“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.
The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.
On Twitter @JessCraig_OP
Pediatric patients diagnosed with pheochromocytomas (PHEO) or paragangliomas (PGL) were nearly three times as likely to also carry a diagnosis of attention deficit hyperactivity disorder (ADHD), compared to pediatric patients without PHEO or PGL, investigators reported.
In addition, in 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.
PHEO and PGL are rare tumors of the adrenal gland. About 10% of PHEO and PGL cases occur in patients younger than 18 years. PHEOs form inside the adrenal gland in the adrenal medulla while PGLs form outside the adrenal gland. Both tumors cause excess secretion of epinephrine and norepinephrine resulting in high blood pressure, headaches, weight loss, excess sweating, anxiety, and depression. These tumors are most often surgically removed or treated with medication. Chemotherapy and radiation therapy have not been as effective in treating PHEO or PGL.
ADHD is a neurodevelopment disorder characterized by a pattern of inattention and hyperactivity or impulsivity. ADHD is associated with catecholamine dysregulation; the function of catecholamine receptors is impaired by either excess or deficient stimulation. ADHD has a prevalence of 7.2% in children aged 4-18.
In addition to the overlap in symptoms, “the stimulants used to treat ADHD may exacerbate the symptoms of the PHEO/PGL and potentially lead to a hypertensive crisis ... Amphetamines, the most widely used ADHD medication class, lead to release of stored catecholamines from vesicles, block reuptake of norepinephrine and dopamine, and block catecholamine degradation,” wrote Dr. M. Batsis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and her associates (Horm Metab Res. 2016 May 12. doi: 10.1055/s-0042-106725).
“I noticed that a lot of patients with the same story as follows: [parents] went to their pediatrician when their child started having feelings of anxiety or their heart was racing. And these symptoms were attributed to ADHD, and the child was started on medications. It wasn’t until later symptoms – an abdominal mass or a hypertensive crisis – that the patient was ultimately found out to have a pheochromocytoma,” Dr. Maya Lodish, a pediatric endocrinologist and coauthor of the paper, said in an interview.
“In hindsight, it just was not picked up. ADHD medications in no way affect tumor growth. The substances that these tumors release are stimulants. Endocrine tumors release catecholamine which are naturally occurring hormones we release under stress. When you add on top of that a stimulant medication [to treat ADHD] that may causes the nervous system to go into overdrive,” she said.
Due to the rarity of PHEO and PGL, their association with ADHD has not been well characterized. The purpose of this study was to therefore better assess the relationship between ADHD and PHEO/PGL development.
Investigators recruited 43 pediatric patients aged 6-17 who had been diagnosed with PHEO or PGL. Twenty-one percent (n = 9) of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328).
Prior to the surgical removal of the tumors, eight of the nine patients had elevated levels of norepinephrine (n = 7), dopamine (n = 3), epinephrine (n = 1), metanephrine (n = 5) and/or normetanephrine (n = 7). In the remaining patient, levels were not measured.
Following the surgical removal of the tumors, three of the nine patients experienced both a resolution of their ADHD-related symptoms and a drop or normalization of their catecholamine and metanephrine levels. Two of those three patients showed no clinical signs of recurrent tumors while the third is under evaluation for a small pelvic lesion.
“These tumors are very rare and the vast majority of patients with ADHD are not affected by them, but they do occur. There are other organic conditions with the same symptoms – drug abuse, medications, Graves disease. If the child has symptoms attributed to ADHD and high blood pressure or family history of endocrine tumors then it is important to have a full organic workup to measure other causes of hypertension prior to starting stimulant medication,” Dr. Lodish said.
“My observation is that, and a lot of articles out there would agree, diagnoses of ADHD are on the rise and the prescribing of ADHD medication is also on the rise. I hope this is a bit of a wake-up call to practitioners that what’s common is common but there are some rare [conditions] to be aware of and so don’t have a knee jerk reaction to prescribing a medication for symptoms believed to be attributed to ADHD,” she said.
The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures to report.
On Twitter @JessCraig_OP
FROM HORMONE AND METABOLIC RESEARCH
Key clinical point: Pediatric patients with pheochromocytomas (PHEO) or paragangliomas (PGL) were more likely to also carry a diagnosis of ADHD, compared to pediatric patients without PHEO or PGL.
Major finding: Twenty-one percent of patients with PHEO/PGL carried a diagnosis of ADHD, compared to 7.2% in the general population (P = .0328). In 33% of the patients with PHEO and PGL, ADHD symptoms were resolved following surgical removal of the tumor.
Data source: Longitudinal study of 43 patients aged 6-17 who were diagnosed with PHEO and/or PGL.
Disclosures: The Division of Intramural Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development supported the study. The investigators had no disclosures.
FDA approves atezolizumab for advanced urothelial carcinoma
The Food and Drug Administration has granted accelerated approval to atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma in patients who experienced disease progression during or following platinum-based chemotherapy, along with a complementary diagnostic.
Atezolizumab, marketed as Tecentriq by Genentech, is the first and only FDA-approved anti-PDL1 immunotherapy for urothelial carcinoma.
This accelerated approval is based on a 14.8% overall response rate (95% confidence interval, 11.1-19.3) reported from the open-label, multicenter, phase II IMvigor clinical trial of 310 patients, the FDA said in a written statement.
Just over one-fourth (26%) of participants who tested positive for PD-L1 expression experienced a tumor response, compared with 9.5% of participants who were negative for PD-L1 expression. The FDA, therefore, also approved the Ventana PD-L1 (SP142) assay to detect PD-L1 protein expression levels on patients’ tumor-infiltrating immune cells, which will help guide treatment decisions.
The most common adverse events reported in the single-arm trail of atezolizumab were urinary tract infection (9%), anemia (8%), fatigue (6%), and difficulty breathing (4%). Other serious side effects included pneumonitis, hepatitis, colitis, hormone gland problems, neuropathy, meningocephalitis, eye problems, severe infections, and severe infusion reactions. Three people (0.9%) experienced sepsis, pneumonitis, or intestinal obstruction that led to death, Genentech reported in a written statement.
On Twitter @JessCraig_OP
The Food and Drug Administration has granted accelerated approval to atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma in patients who experienced disease progression during or following platinum-based chemotherapy, along with a complementary diagnostic.
Atezolizumab, marketed as Tecentriq by Genentech, is the first and only FDA-approved anti-PDL1 immunotherapy for urothelial carcinoma.
This accelerated approval is based on a 14.8% overall response rate (95% confidence interval, 11.1-19.3) reported from the open-label, multicenter, phase II IMvigor clinical trial of 310 patients, the FDA said in a written statement.
Just over one-fourth (26%) of participants who tested positive for PD-L1 expression experienced a tumor response, compared with 9.5% of participants who were negative for PD-L1 expression. The FDA, therefore, also approved the Ventana PD-L1 (SP142) assay to detect PD-L1 protein expression levels on patients’ tumor-infiltrating immune cells, which will help guide treatment decisions.
The most common adverse events reported in the single-arm trail of atezolizumab were urinary tract infection (9%), anemia (8%), fatigue (6%), and difficulty breathing (4%). Other serious side effects included pneumonitis, hepatitis, colitis, hormone gland problems, neuropathy, meningocephalitis, eye problems, severe infections, and severe infusion reactions. Three people (0.9%) experienced sepsis, pneumonitis, or intestinal obstruction that led to death, Genentech reported in a written statement.
On Twitter @JessCraig_OP
The Food and Drug Administration has granted accelerated approval to atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma in patients who experienced disease progression during or following platinum-based chemotherapy, along with a complementary diagnostic.
Atezolizumab, marketed as Tecentriq by Genentech, is the first and only FDA-approved anti-PDL1 immunotherapy for urothelial carcinoma.
This accelerated approval is based on a 14.8% overall response rate (95% confidence interval, 11.1-19.3) reported from the open-label, multicenter, phase II IMvigor clinical trial of 310 patients, the FDA said in a written statement.
Just over one-fourth (26%) of participants who tested positive for PD-L1 expression experienced a tumor response, compared with 9.5% of participants who were negative for PD-L1 expression. The FDA, therefore, also approved the Ventana PD-L1 (SP142) assay to detect PD-L1 protein expression levels on patients’ tumor-infiltrating immune cells, which will help guide treatment decisions.
The most common adverse events reported in the single-arm trail of atezolizumab were urinary tract infection (9%), anemia (8%), fatigue (6%), and difficulty breathing (4%). Other serious side effects included pneumonitis, hepatitis, colitis, hormone gland problems, neuropathy, meningocephalitis, eye problems, severe infections, and severe infusion reactions. Three people (0.9%) experienced sepsis, pneumonitis, or intestinal obstruction that led to death, Genentech reported in a written statement.
On Twitter @JessCraig_OP
Validated tool outperforms KPS in predicting chemo toxicity in older adults
The risk of chemotherapy toxicity is high in older adults with cancer, and a validated tool now exists to assess this toxicity in everyday practice to aid in clinical decision making, investigators reported.
To validate a previously developed model, investigators recruited 250 patients with solid tumors who were aged 65 years of age and older and scheduled to receive a new chemotherapy regimen, and compared results to 500 patients in the development cohort. Patients were observed through the chemotherapy course, and adverse events were obtained from chart review.
“In both the development and validation cohorts, this model had a greater ability to discriminate toxicity risk in older adults than did the present standard oncologic assessment of performance status, the KPS [Karnofsky Performance Status] score,” wrote Dr. Arti Hurria of the City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, Calif., and her associates (J Clin Oncol. 2016 May 16. doi: 10.1200/JCO.2015.65.4327).
“Hence, this study fills a gap in knowledge by developing a validated tool to assess chemotherapy toxicity risk among older adults who receive chemotherapy in everyday practice to aid in clinical decision making,” they said.
The predictive model incorporates factors obtained in everyday oncology (patient age, number and dosing regimen of chemotherapy drugs) with various factors pertaining to geriatric health, such as the number of falls in 6 months, ability to take one’s own medication, and mobility.
More than half of the patients in the validation cohort (58%) experienced grade 3-5 toxicity, compared with 53% of patients in the development cohort. In the validation cohort, risk of toxicity increased with increasing risk score from the predictive model and was statistically significant (36.7% in the low-risk group, 62.4% in the medium-risk group, and 70.2% in the high-risk group (P less than .001).
Physician-rated KPS was not predictive of chemotherapy toxicity in either development cohort (P = .19) or the validation cohort (P = .25).
The two cohorts differed significantly by cancer type and stage; the development cohort had more patients with gynecologic cancer (17% vs. 7% in the validation cohort) while breast cancer was more common in the validation cohort (24% vs 11% in the development cohort).
The validity of the model was assessed by creating receiver-operating characteristic curves and calculating the area under the curve. The area under the curve in the validation cohort (0.65; 95% confidence interval, 0.58-0.71) and the area under the curve in the developmental cohort (0.72; 95% CI, 0.68-0.77) were not statistically different (P = .09).
This study was supported by the National Institutes of Health, the National Institute on Aging, the Paul Beeson Career Development Award in Aging Research, the American Society of Clinical Oncology, the Association of Specialty Professors, and the Junior Development Award in Geriatric Oncology. Four of the investigators reported receiving funding from or having consulting or advisory roles with various companies.
On Twitter @JessCraig_OP
The risk of chemotherapy toxicity is high in older adults with cancer, and a validated tool now exists to assess this toxicity in everyday practice to aid in clinical decision making, investigators reported.
To validate a previously developed model, investigators recruited 250 patients with solid tumors who were aged 65 years of age and older and scheduled to receive a new chemotherapy regimen, and compared results to 500 patients in the development cohort. Patients were observed through the chemotherapy course, and adverse events were obtained from chart review.
“In both the development and validation cohorts, this model had a greater ability to discriminate toxicity risk in older adults than did the present standard oncologic assessment of performance status, the KPS [Karnofsky Performance Status] score,” wrote Dr. Arti Hurria of the City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, Calif., and her associates (J Clin Oncol. 2016 May 16. doi: 10.1200/JCO.2015.65.4327).
“Hence, this study fills a gap in knowledge by developing a validated tool to assess chemotherapy toxicity risk among older adults who receive chemotherapy in everyday practice to aid in clinical decision making,” they said.
The predictive model incorporates factors obtained in everyday oncology (patient age, number and dosing regimen of chemotherapy drugs) with various factors pertaining to geriatric health, such as the number of falls in 6 months, ability to take one’s own medication, and mobility.
More than half of the patients in the validation cohort (58%) experienced grade 3-5 toxicity, compared with 53% of patients in the development cohort. In the validation cohort, risk of toxicity increased with increasing risk score from the predictive model and was statistically significant (36.7% in the low-risk group, 62.4% in the medium-risk group, and 70.2% in the high-risk group (P less than .001).
Physician-rated KPS was not predictive of chemotherapy toxicity in either development cohort (P = .19) or the validation cohort (P = .25).
The two cohorts differed significantly by cancer type and stage; the development cohort had more patients with gynecologic cancer (17% vs. 7% in the validation cohort) while breast cancer was more common in the validation cohort (24% vs 11% in the development cohort).
The validity of the model was assessed by creating receiver-operating characteristic curves and calculating the area under the curve. The area under the curve in the validation cohort (0.65; 95% confidence interval, 0.58-0.71) and the area under the curve in the developmental cohort (0.72; 95% CI, 0.68-0.77) were not statistically different (P = .09).
This study was supported by the National Institutes of Health, the National Institute on Aging, the Paul Beeson Career Development Award in Aging Research, the American Society of Clinical Oncology, the Association of Specialty Professors, and the Junior Development Award in Geriatric Oncology. Four of the investigators reported receiving funding from or having consulting or advisory roles with various companies.
On Twitter @JessCraig_OP
The risk of chemotherapy toxicity is high in older adults with cancer, and a validated tool now exists to assess this toxicity in everyday practice to aid in clinical decision making, investigators reported.
To validate a previously developed model, investigators recruited 250 patients with solid tumors who were aged 65 years of age and older and scheduled to receive a new chemotherapy regimen, and compared results to 500 patients in the development cohort. Patients were observed through the chemotherapy course, and adverse events were obtained from chart review.
“In both the development and validation cohorts, this model had a greater ability to discriminate toxicity risk in older adults than did the present standard oncologic assessment of performance status, the KPS [Karnofsky Performance Status] score,” wrote Dr. Arti Hurria of the City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, Calif., and her associates (J Clin Oncol. 2016 May 16. doi: 10.1200/JCO.2015.65.4327).
“Hence, this study fills a gap in knowledge by developing a validated tool to assess chemotherapy toxicity risk among older adults who receive chemotherapy in everyday practice to aid in clinical decision making,” they said.
The predictive model incorporates factors obtained in everyday oncology (patient age, number and dosing regimen of chemotherapy drugs) with various factors pertaining to geriatric health, such as the number of falls in 6 months, ability to take one’s own medication, and mobility.
More than half of the patients in the validation cohort (58%) experienced grade 3-5 toxicity, compared with 53% of patients in the development cohort. In the validation cohort, risk of toxicity increased with increasing risk score from the predictive model and was statistically significant (36.7% in the low-risk group, 62.4% in the medium-risk group, and 70.2% in the high-risk group (P less than .001).
Physician-rated KPS was not predictive of chemotherapy toxicity in either development cohort (P = .19) or the validation cohort (P = .25).
The two cohorts differed significantly by cancer type and stage; the development cohort had more patients with gynecologic cancer (17% vs. 7% in the validation cohort) while breast cancer was more common in the validation cohort (24% vs 11% in the development cohort).
The validity of the model was assessed by creating receiver-operating characteristic curves and calculating the area under the curve. The area under the curve in the validation cohort (0.65; 95% confidence interval, 0.58-0.71) and the area under the curve in the developmental cohort (0.72; 95% CI, 0.68-0.77) were not statistically different (P = .09).
This study was supported by the National Institutes of Health, the National Institute on Aging, the Paul Beeson Career Development Award in Aging Research, the American Society of Clinical Oncology, the Association of Specialty Professors, and the Junior Development Award in Geriatric Oncology. Four of the investigators reported receiving funding from or having consulting or advisory roles with various companies.
On Twitter @JessCraig_OP
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Investigators validated a mathematical model that successfully predicts chemotherapy toxicity in cancer patients aged 65 years or older.
Major finding: The area under the receiver-operating characteristic curve in the validation cohort (0.65; 95% CI, 0.58-0.71) and the area under the ROC curve in the developmental cohort (0.72; 95% CI, 0.68-0.77) were not statistically different (P = .09).
Data source: A longitudinal study of 250 patients older than 65 years.
Disclosures: This study was supported by the National Institutes of Health, the National Institute on Aging, the Paul Beeson Career Development Award in Aging Research, the American Society of Clinical Oncology, the Association of Specialty Professors, and the Junior Development Award in Geriatric Oncology. Four of the investigators reported receiving funding from or having consulting or advisory roles with various companies.
Pembrolizumab benefit holds long-term for some melanoma patients
The anti–PD-1 immunotherapy pembrolizumab increases long-term survival in some patients with advanced melanoma, according to updated results of KEYNOTE-001.
Among the 655 patients studied in the phase 1b trial, the 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%, Dr. Caroline Robert reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Median overall survival was 24.4 months. Before 2011, patients with advanced melanoma had a median overall survival of less than one year, said Dr. Robert, head of the dermatology unit at the Institut Gustave-Roussy in Paris.
Study participants received pembrolizumab at either 2 or 10 mg/kg every 3 weeks. During the trial, 2 mg/kg every 3 weeks was determined to be the optimal dosing regimen. Patients remained on the treatment until disease progression, intolerable toxicity, or investigator decision. Eight percent of patients stopped treatment due to drug-related symptoms, and there were no drug-related deaths.
Survival rates differed slightly based on prior melanoma treatment. Of the 655 patients in the study, 75% had received previous treatments; patients who had not received prior treatment had slightly higher survival at 45%.
Overall response rate was 33%. Responses were durable as 73% of patients had a response rate of two or more years. Ninety-five patients had a complete response, and 61 of those patients stopped treatment following the complete response.
“I really hope for a cure for these people,” Dr. Robert said.
Pembrolizumab was generally well tolerated with the most common adverse events being fatigue (40%), itchiness (28%), and rash (23%).
ASCO spokesperson and moderator, Dr. Don Dizon, said the results of this study are “incredibly exciting given they came from a phase I trial. This is a new treatment and the longest follow-up of people [with melanoma] who have received pembrolizumab.” Dr. Dizon hopes to “potentially see a cure [for] melanoma” given the reported durability and response rate to the drug.
On Twitter @JessCraig_OP
The anti–PD-1 immunotherapy pembrolizumab increases long-term survival in some patients with advanced melanoma, according to updated results of KEYNOTE-001.
Among the 655 patients studied in the phase 1b trial, the 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%, Dr. Caroline Robert reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Median overall survival was 24.4 months. Before 2011, patients with advanced melanoma had a median overall survival of less than one year, said Dr. Robert, head of the dermatology unit at the Institut Gustave-Roussy in Paris.
Study participants received pembrolizumab at either 2 or 10 mg/kg every 3 weeks. During the trial, 2 mg/kg every 3 weeks was determined to be the optimal dosing regimen. Patients remained on the treatment until disease progression, intolerable toxicity, or investigator decision. Eight percent of patients stopped treatment due to drug-related symptoms, and there were no drug-related deaths.
Survival rates differed slightly based on prior melanoma treatment. Of the 655 patients in the study, 75% had received previous treatments; patients who had not received prior treatment had slightly higher survival at 45%.
Overall response rate was 33%. Responses were durable as 73% of patients had a response rate of two or more years. Ninety-five patients had a complete response, and 61 of those patients stopped treatment following the complete response.
“I really hope for a cure for these people,” Dr. Robert said.
Pembrolizumab was generally well tolerated with the most common adverse events being fatigue (40%), itchiness (28%), and rash (23%).
ASCO spokesperson and moderator, Dr. Don Dizon, said the results of this study are “incredibly exciting given they came from a phase I trial. This is a new treatment and the longest follow-up of people [with melanoma] who have received pembrolizumab.” Dr. Dizon hopes to “potentially see a cure [for] melanoma” given the reported durability and response rate to the drug.
On Twitter @JessCraig_OP
The anti–PD-1 immunotherapy pembrolizumab increases long-term survival in some patients with advanced melanoma, according to updated results of KEYNOTE-001.
Among the 655 patients studied in the phase 1b trial, the 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%, Dr. Caroline Robert reported in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
Median overall survival was 24.4 months. Before 2011, patients with advanced melanoma had a median overall survival of less than one year, said Dr. Robert, head of the dermatology unit at the Institut Gustave-Roussy in Paris.
Study participants received pembrolizumab at either 2 or 10 mg/kg every 3 weeks. During the trial, 2 mg/kg every 3 weeks was determined to be the optimal dosing regimen. Patients remained on the treatment until disease progression, intolerable toxicity, or investigator decision. Eight percent of patients stopped treatment due to drug-related symptoms, and there were no drug-related deaths.
Survival rates differed slightly based on prior melanoma treatment. Of the 655 patients in the study, 75% had received previous treatments; patients who had not received prior treatment had slightly higher survival at 45%.
Overall response rate was 33%. Responses were durable as 73% of patients had a response rate of two or more years. Ninety-five patients had a complete response, and 61 of those patients stopped treatment following the complete response.
“I really hope for a cure for these people,” Dr. Robert said.
Pembrolizumab was generally well tolerated with the most common adverse events being fatigue (40%), itchiness (28%), and rash (23%).
ASCO spokesperson and moderator, Dr. Don Dizon, said the results of this study are “incredibly exciting given they came from a phase I trial. This is a new treatment and the longest follow-up of people [with melanoma] who have received pembrolizumab.” Dr. Dizon hopes to “potentially see a cure [for] melanoma” given the reported durability and response rate to the drug.
On Twitter @JessCraig_OP
FROM THE 2016 ASCO ANNUAL MEETING
Key clinical point: Pembrolizumab increases long-term survival in some patients with advanced melanoma.
Major finding: The 3-year overall survival rate for advanced melanoma patients treated with pembrolizumab was 40%. The median overall survival was 24.4 months.
Data source: A phase Ib clinical trial of 655 patients with advanced melanoma.
Disclosures: This study was funded by Merck. All of the investigators reported serving in advisory/consultatory roles for, having stock in, or receiving financial compensation or honoraria from several companies.
Early palliative care for cancer patients benefits caregivers
Introducing palliative care in combination with standard oncology care immediately following a cancer diagnosis results in improved quality of life and lower incidence of depression for caregivers of cancer patients.
“The integration of palliative care can improve patient care but the evidence is lacking about whether or not there are benefits [for] caregivers,” Dr. Areej El-Jawahri of Massachusetts General Hospital, Boston, said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“This study suggests that early palliative care creates a powerful positive feedback loop in families facing cancer. While patients receive a direct benefit from early palliative care, their caregivers experience a positive downstream effect, which may make it easier for them to care for their loved ones,” she said.
Investigators enrolled 275 family caregivers of patients newly diagnosed with incurable lung or gastrointestinal cancers. Patients were randomly assigned to receive early palliative care in addition to standard oncology care or to receive standard oncology care alone.
Palliative care involved a multifaceted team including nurses, social workers, and psychologists. The palliative care intervention was patient focused, and caregivers, who were defined as a relative or friend identified by the patient as the primary caregiver, were not required to attend palliative care appointments. However, about 50% of caregivers did attend, according to Dr. El-Jawahri.
At time of enrollment and then at time points 12 and 14 weeks post enrollment, caregivers completed standard questionnaires, the 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale, that assessed quality of life and mood.
Twelve weeks after the cancer diagnosis, caregivers who received early palliative care reported significantly lower depression symptoms while vitality and social functioning improved. For patients who did not receive early palliative care, their caregivers’ vitality and social functioning decreased.
“This is the first study showing a positive impact of a patient-focused palliative care intervention on family caregivers,” said Dr. El-Jawahri.
“This study really points out that we have so many ways to help our patients and their families,” Dr. Julie Vose, president of ASCO, said during the presscast.
On Twitter @JessCraig_OP
Introducing palliative care in combination with standard oncology care immediately following a cancer diagnosis results in improved quality of life and lower incidence of depression for caregivers of cancer patients.
“The integration of palliative care can improve patient care but the evidence is lacking about whether or not there are benefits [for] caregivers,” Dr. Areej El-Jawahri of Massachusetts General Hospital, Boston, said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“This study suggests that early palliative care creates a powerful positive feedback loop in families facing cancer. While patients receive a direct benefit from early palliative care, their caregivers experience a positive downstream effect, which may make it easier for them to care for their loved ones,” she said.
Investigators enrolled 275 family caregivers of patients newly diagnosed with incurable lung or gastrointestinal cancers. Patients were randomly assigned to receive early palliative care in addition to standard oncology care or to receive standard oncology care alone.
Palliative care involved a multifaceted team including nurses, social workers, and psychologists. The palliative care intervention was patient focused, and caregivers, who were defined as a relative or friend identified by the patient as the primary caregiver, were not required to attend palliative care appointments. However, about 50% of caregivers did attend, according to Dr. El-Jawahri.
At time of enrollment and then at time points 12 and 14 weeks post enrollment, caregivers completed standard questionnaires, the 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale, that assessed quality of life and mood.
Twelve weeks after the cancer diagnosis, caregivers who received early palliative care reported significantly lower depression symptoms while vitality and social functioning improved. For patients who did not receive early palliative care, their caregivers’ vitality and social functioning decreased.
“This is the first study showing a positive impact of a patient-focused palliative care intervention on family caregivers,” said Dr. El-Jawahri.
“This study really points out that we have so many ways to help our patients and their families,” Dr. Julie Vose, president of ASCO, said during the presscast.
On Twitter @JessCraig_OP
Introducing palliative care in combination with standard oncology care immediately following a cancer diagnosis results in improved quality of life and lower incidence of depression for caregivers of cancer patients.
“The integration of palliative care can improve patient care but the evidence is lacking about whether or not there are benefits [for] caregivers,” Dr. Areej El-Jawahri of Massachusetts General Hospital, Boston, said in a presscast leading up to the annual meeting of the American Society of Clinical Oncology.
“This study suggests that early palliative care creates a powerful positive feedback loop in families facing cancer. While patients receive a direct benefit from early palliative care, their caregivers experience a positive downstream effect, which may make it easier for them to care for their loved ones,” she said.
Investigators enrolled 275 family caregivers of patients newly diagnosed with incurable lung or gastrointestinal cancers. Patients were randomly assigned to receive early palliative care in addition to standard oncology care or to receive standard oncology care alone.
Palliative care involved a multifaceted team including nurses, social workers, and psychologists. The palliative care intervention was patient focused, and caregivers, who were defined as a relative or friend identified by the patient as the primary caregiver, were not required to attend palliative care appointments. However, about 50% of caregivers did attend, according to Dr. El-Jawahri.
At time of enrollment and then at time points 12 and 14 weeks post enrollment, caregivers completed standard questionnaires, the 36-Item Short Form Health Survey and the Hospital Anxiety and Depression Scale, that assessed quality of life and mood.
Twelve weeks after the cancer diagnosis, caregivers who received early palliative care reported significantly lower depression symptoms while vitality and social functioning improved. For patients who did not receive early palliative care, their caregivers’ vitality and social functioning decreased.
“This is the first study showing a positive impact of a patient-focused palliative care intervention on family caregivers,” said Dr. El-Jawahri.
“This study really points out that we have so many ways to help our patients and their families,” Dr. Julie Vose, president of ASCO, said during the presscast.
On Twitter @JessCraig_OP
FROM THE 2016 ASCO ANNUAL MEETING
Key clinical point: Early palliative care for cancer patients improved quality of life and lowered the incidence of depression for caregivers.
Major finding: After 12 weeks, caregivers of patients who received early palliative care reported significantly lower depression symptoms. Vitality and social functioning also improved.
Data source: A randomized clinical trial of 275 family caregivers of patients newly diagnosed with incurable lung or gastrointestinal cancers.
Disclosures: The National Institutes of Health funded the study. Three of the investigators reported serving in advisory roles or receiving financial compensation or honoraria from several companies.
No benefit from added trabectedin for STS patients
When trabectedin was administered to soft tissue sarcoma (STS) patients receiving doxorubicin, neither progression-free nor overall survival significantly improved, investigators found.
In addition, patients who received both drugs were significantly more likely to experience adverse events.
“The combination of trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS patients, at least under this schedule. Moreover, the experimental arm was significantly more toxic than the control arm, especially regarding thrombocytopenia, vomiting, liver toxicity, and asthenia,” wrote Dr. Javier Martin-Broto of the Virgen del Rocio Hospital and Biomedicine Institute, Seville (Spain) and his associates (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.65.3329).
Of 115 adult patients with advanced nonresectable or metastatic STS, 59 received doxorubicin only, 55 received both doxorubicin and trabectedin, and one patient was not treated. In the experimental group, doxorubicin was administered before trabectedin. Both the experimental and control groups underwent six cycles of their respective drug regime unless disease progression or unacceptable toxicity was observed.
A Cox proportional hazard regression model revealed that the progression-free survival was not significantly higher among patients receiving trabectedin and doxorubicin compared to patients only receiving doxorubicin (5.7 months vs. 5.5 months; hazard ratio, 1.16; 95% confidence interval, 0.79-1.71; P = .45). Overall survival was also not significantly different between the groups (13.3 months vs. 13.7 months; HR, 1.21; 95% CI, .77-1.92, P = .41).
However, compared with patients who only received doxorubicin, patients who received both trabectedin and doxorubicin experienced significantly more adverse events such as grade 3 or 4 thrombocytopenia (2% vs. 18%, P = .016), grade 3 or 4 liver toxicity (12% vs. 29%, P = .002), AST (0% vs. 8%, P = .007), ALT (0% vs. 19%, P less than .001), and grade 3 or 4 asthenia (4% vs. 25%, P = .002).
On Twitter @jess_craig94
When trabectedin was administered to soft tissue sarcoma (STS) patients receiving doxorubicin, neither progression-free nor overall survival significantly improved, investigators found.
In addition, patients who received both drugs were significantly more likely to experience adverse events.
“The combination of trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS patients, at least under this schedule. Moreover, the experimental arm was significantly more toxic than the control arm, especially regarding thrombocytopenia, vomiting, liver toxicity, and asthenia,” wrote Dr. Javier Martin-Broto of the Virgen del Rocio Hospital and Biomedicine Institute, Seville (Spain) and his associates (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.65.3329).
Of 115 adult patients with advanced nonresectable or metastatic STS, 59 received doxorubicin only, 55 received both doxorubicin and trabectedin, and one patient was not treated. In the experimental group, doxorubicin was administered before trabectedin. Both the experimental and control groups underwent six cycles of their respective drug regime unless disease progression or unacceptable toxicity was observed.
A Cox proportional hazard regression model revealed that the progression-free survival was not significantly higher among patients receiving trabectedin and doxorubicin compared to patients only receiving doxorubicin (5.7 months vs. 5.5 months; hazard ratio, 1.16; 95% confidence interval, 0.79-1.71; P = .45). Overall survival was also not significantly different between the groups (13.3 months vs. 13.7 months; HR, 1.21; 95% CI, .77-1.92, P = .41).
However, compared with patients who only received doxorubicin, patients who received both trabectedin and doxorubicin experienced significantly more adverse events such as grade 3 or 4 thrombocytopenia (2% vs. 18%, P = .016), grade 3 or 4 liver toxicity (12% vs. 29%, P = .002), AST (0% vs. 8%, P = .007), ALT (0% vs. 19%, P less than .001), and grade 3 or 4 asthenia (4% vs. 25%, P = .002).
On Twitter @jess_craig94
When trabectedin was administered to soft tissue sarcoma (STS) patients receiving doxorubicin, neither progression-free nor overall survival significantly improved, investigators found.
In addition, patients who received both drugs were significantly more likely to experience adverse events.
“The combination of trabectedin plus doxorubicin did not show superiority over doxorubicin alone as first-line treatment of advanced STS patients, at least under this schedule. Moreover, the experimental arm was significantly more toxic than the control arm, especially regarding thrombocytopenia, vomiting, liver toxicity, and asthenia,” wrote Dr. Javier Martin-Broto of the Virgen del Rocio Hospital and Biomedicine Institute, Seville (Spain) and his associates (J Clin Oncol. 2016. doi: 10.1200/JCO.2015.65.3329).
Of 115 adult patients with advanced nonresectable or metastatic STS, 59 received doxorubicin only, 55 received both doxorubicin and trabectedin, and one patient was not treated. In the experimental group, doxorubicin was administered before trabectedin. Both the experimental and control groups underwent six cycles of their respective drug regime unless disease progression or unacceptable toxicity was observed.
A Cox proportional hazard regression model revealed that the progression-free survival was not significantly higher among patients receiving trabectedin and doxorubicin compared to patients only receiving doxorubicin (5.7 months vs. 5.5 months; hazard ratio, 1.16; 95% confidence interval, 0.79-1.71; P = .45). Overall survival was also not significantly different between the groups (13.3 months vs. 13.7 months; HR, 1.21; 95% CI, .77-1.92, P = .41).
However, compared with patients who only received doxorubicin, patients who received both trabectedin and doxorubicin experienced significantly more adverse events such as grade 3 or 4 thrombocytopenia (2% vs. 18%, P = .016), grade 3 or 4 liver toxicity (12% vs. 29%, P = .002), AST (0% vs. 8%, P = .007), ALT (0% vs. 19%, P less than .001), and grade 3 or 4 asthenia (4% vs. 25%, P = .002).
On Twitter @jess_craig94
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: When trabectedin was administered to soft tissue sarcoma (STS) patients receiving doxorubicin, neither progression-free nor overall survival significantly improved. However, patients who received both drugs were significantly more likely to experience adverse events.
Major finding: Progression-free survival was not significantly higher among patients receiving trabectedin and doxorubicin, compared with patients only receiving doxorubicin (5.7 months vs. 5.5 months; HR, 1.16; 95% CI, 0.79-1.71; P = .45). Compared with patients who only received doxorubicin, patients who received both drugs experienced significantly more adverse events such as thrombocytopenia, liver toxicity, AST, ALT, and asthenia (all P values less than .05).
Data source: Randomized phase II trial of 115 adult patients with advanced nonresectable soft tissue sarcoma.
Disclosures: This study was supported by the Spanish Group for Research on Sarcoma. Ten investigators reported serving in advisory roles or receiving financial compensation or honoraria from several companies. The other 14 investigators reported having no disclosures.
FDA approves lenvatinib for advanced renal cell carcinoma
The Food and Drug Administration has approved lenvatinib capsules, in combination with everolimus, for the treatment of patients with advanced renal cell carcinoma following one prior antiangiogenic therapy.
Approval was based on prolonged progression-free survival (PFS) in a randomized, phase II, open-label multicenter clinical trial of 153 patients, the FDA said in a written statement.
Patients who received lenvatinib plus everolimus (n = 51) had significantly prolonged PFS, compared with patients who received only everolimus (n = 50) (14.6 months vs. 5.5 months; HR, 0.40; 95% CI, 0.24-0.68; P = .0005) but not compared with patients who received lenvatinib alone (n = 52) (7.4 months; HR, 0.66; 95% CI, 0.30-1.10; P = .12). Of patients receiving the combination of drugs, 71% experienced adverse events, compared with 79% of patients receiving lenvatinib alone and 50% of patients receiving everolimus alone. The most common treatment-related adverse events reported included diarrhea, decreased appetite, and severe fatigue.
The FDA previously granted lenvatinib, marketed as Lenvima by Eisai, a breakthrough therapy designation and priority review.
“This is the only combination regimen to significantly prolong progression-free survival … when compared with a standard of care in patients with advanced renal cell carcinoma,” representatives from Eisai said in a written statement.
Lenvatinib was previously approved for the treatment of recurrent, progressive, radioactive iodine-refractory differentiated thyroid cancer in early 2015. However, in April 2016, the FDA released a safety warning about lenvatinib capsules for oral use.
“Serious tumor-related bleeds, including fatal hemorrhagic events in Lenvima-treated patients, have occurred in clinical trials and been reported in postmarketing experience,” reported the FDA in a written statement.
The recommended lenvatinib dosage for renal cell carcinoma patients is 18 mg/day, lower than the 24 mg/day that was recommended to thyroid cancer patients prior to the FDA’s warning.
On Twitter @JessCraig_OP
The Food and Drug Administration has approved lenvatinib capsules, in combination with everolimus, for the treatment of patients with advanced renal cell carcinoma following one prior antiangiogenic therapy.
Approval was based on prolonged progression-free survival (PFS) in a randomized, phase II, open-label multicenter clinical trial of 153 patients, the FDA said in a written statement.
Patients who received lenvatinib plus everolimus (n = 51) had significantly prolonged PFS, compared with patients who received only everolimus (n = 50) (14.6 months vs. 5.5 months; HR, 0.40; 95% CI, 0.24-0.68; P = .0005) but not compared with patients who received lenvatinib alone (n = 52) (7.4 months; HR, 0.66; 95% CI, 0.30-1.10; P = .12). Of patients receiving the combination of drugs, 71% experienced adverse events, compared with 79% of patients receiving lenvatinib alone and 50% of patients receiving everolimus alone. The most common treatment-related adverse events reported included diarrhea, decreased appetite, and severe fatigue.
The FDA previously granted lenvatinib, marketed as Lenvima by Eisai, a breakthrough therapy designation and priority review.
“This is the only combination regimen to significantly prolong progression-free survival … when compared with a standard of care in patients with advanced renal cell carcinoma,” representatives from Eisai said in a written statement.
Lenvatinib was previously approved for the treatment of recurrent, progressive, radioactive iodine-refractory differentiated thyroid cancer in early 2015. However, in April 2016, the FDA released a safety warning about lenvatinib capsules for oral use.
“Serious tumor-related bleeds, including fatal hemorrhagic events in Lenvima-treated patients, have occurred in clinical trials and been reported in postmarketing experience,” reported the FDA in a written statement.
The recommended lenvatinib dosage for renal cell carcinoma patients is 18 mg/day, lower than the 24 mg/day that was recommended to thyroid cancer patients prior to the FDA’s warning.
On Twitter @JessCraig_OP
The Food and Drug Administration has approved lenvatinib capsules, in combination with everolimus, for the treatment of patients with advanced renal cell carcinoma following one prior antiangiogenic therapy.
Approval was based on prolonged progression-free survival (PFS) in a randomized, phase II, open-label multicenter clinical trial of 153 patients, the FDA said in a written statement.
Patients who received lenvatinib plus everolimus (n = 51) had significantly prolonged PFS, compared with patients who received only everolimus (n = 50) (14.6 months vs. 5.5 months; HR, 0.40; 95% CI, 0.24-0.68; P = .0005) but not compared with patients who received lenvatinib alone (n = 52) (7.4 months; HR, 0.66; 95% CI, 0.30-1.10; P = .12). Of patients receiving the combination of drugs, 71% experienced adverse events, compared with 79% of patients receiving lenvatinib alone and 50% of patients receiving everolimus alone. The most common treatment-related adverse events reported included diarrhea, decreased appetite, and severe fatigue.
The FDA previously granted lenvatinib, marketed as Lenvima by Eisai, a breakthrough therapy designation and priority review.
“This is the only combination regimen to significantly prolong progression-free survival … when compared with a standard of care in patients with advanced renal cell carcinoma,” representatives from Eisai said in a written statement.
Lenvatinib was previously approved for the treatment of recurrent, progressive, radioactive iodine-refractory differentiated thyroid cancer in early 2015. However, in April 2016, the FDA released a safety warning about lenvatinib capsules for oral use.
“Serious tumor-related bleeds, including fatal hemorrhagic events in Lenvima-treated patients, have occurred in clinical trials and been reported in postmarketing experience,” reported the FDA in a written statement.
The recommended lenvatinib dosage for renal cell carcinoma patients is 18 mg/day, lower than the 24 mg/day that was recommended to thyroid cancer patients prior to the FDA’s warning.
On Twitter @JessCraig_OP
Gene variation affects survival benefits with cetuximab in colorectal cancer
Patients with the H/H genotype in the FCGR2A gene have higher survival rates when treated with cetuximab than do patients with the H/R and R/R genotypes, investigators reported.
In addition, polymorphism in the FCGR3A gene had no effect on survival.
“Only a proportion of patients with colorectal cancer receiving cetuximab derive benefit from the drug. However, other than RAS and BRAF mutations, no biomarkers have been identified as clinically useful predictors of response to cetuximab. Our primary objective was to determine whether survival is affected by a significant interaction between FCGR polymorphism and cetuximab treatment after adjusting for other potential prognostic factors,” wrote Dr. Geoffrey Liu of the University of Toronto and his associates (Clin Cancer Res. 2016 May 15;22:2435-44).
Cetuximab is a therapeutic monoclonal antibody that inhibits epidermal growth factor receptors by binding to their extracellular domain. Cetuximab also induces antibody-dependent cell cytotoxicity and promotes the endocytic and phagocytic activity in immune cells by binding to the Fc-gamma receptor (FCGR) of host effector cells. FCGR has a genetic polymorphism in the coding region of the FCGR2A gene that causes an amino acid change from histidine (H) to arginine (R). FCGR also has a genetic polymorphism in the coding region of the FCGR3A gene that causes an amino acid change from phenylalinine (F) to valine (V).
Dr. Liu and associates collected patient demographic information and clinical outcome data (overall survival and progression-free survival) from the NCIC CTG CO.17 database and tumor tissue samples from the NCIC CTG central tumor bank. DNA was genotyped blindly. From an original cohort of 572 patients with colorectal cancer, 286 patients had usable FCGR2A genetic data, and 288 patients had usable FCGR3A genetic data. Genetic polymorphisms were not associated with age, sex, performance status, disease site, prior therapies, and site/number of metastatic sites.
In Cox proportional hazard models controlling for clinically relevant factors, patients with the H/H genotype (HR, 7.95; 95% CI, 5.2-10.6) had greater survival benefits than patients with the H/R (HR, 6.6; 95% CI, 5.0-9.1) or R/R (HR, 6.34; 95% CI, 4.5-9.1) genotypes when treated with cetuximab (P = .01). There were no significant relationships between overall or progression-free survival and FCGR3A polymorphisms.
“This prognostic observation should be replicated in other colorectal cancer populations and possibly in other cancers, such as breast cancer or lymphoma, before being generalized into other settings,” the investigators wrote.
On Twitter @jess_craig94
Patients with the H/H genotype in the FCGR2A gene have higher survival rates when treated with cetuximab than do patients with the H/R and R/R genotypes, investigators reported.
In addition, polymorphism in the FCGR3A gene had no effect on survival.
“Only a proportion of patients with colorectal cancer receiving cetuximab derive benefit from the drug. However, other than RAS and BRAF mutations, no biomarkers have been identified as clinically useful predictors of response to cetuximab. Our primary objective was to determine whether survival is affected by a significant interaction between FCGR polymorphism and cetuximab treatment after adjusting for other potential prognostic factors,” wrote Dr. Geoffrey Liu of the University of Toronto and his associates (Clin Cancer Res. 2016 May 15;22:2435-44).
Cetuximab is a therapeutic monoclonal antibody that inhibits epidermal growth factor receptors by binding to their extracellular domain. Cetuximab also induces antibody-dependent cell cytotoxicity and promotes the endocytic and phagocytic activity in immune cells by binding to the Fc-gamma receptor (FCGR) of host effector cells. FCGR has a genetic polymorphism in the coding region of the FCGR2A gene that causes an amino acid change from histidine (H) to arginine (R). FCGR also has a genetic polymorphism in the coding region of the FCGR3A gene that causes an amino acid change from phenylalinine (F) to valine (V).
Dr. Liu and associates collected patient demographic information and clinical outcome data (overall survival and progression-free survival) from the NCIC CTG CO.17 database and tumor tissue samples from the NCIC CTG central tumor bank. DNA was genotyped blindly. From an original cohort of 572 patients with colorectal cancer, 286 patients had usable FCGR2A genetic data, and 288 patients had usable FCGR3A genetic data. Genetic polymorphisms were not associated with age, sex, performance status, disease site, prior therapies, and site/number of metastatic sites.
In Cox proportional hazard models controlling for clinically relevant factors, patients with the H/H genotype (HR, 7.95; 95% CI, 5.2-10.6) had greater survival benefits than patients with the H/R (HR, 6.6; 95% CI, 5.0-9.1) or R/R (HR, 6.34; 95% CI, 4.5-9.1) genotypes when treated with cetuximab (P = .01). There were no significant relationships between overall or progression-free survival and FCGR3A polymorphisms.
“This prognostic observation should be replicated in other colorectal cancer populations and possibly in other cancers, such as breast cancer or lymphoma, before being generalized into other settings,” the investigators wrote.
On Twitter @jess_craig94
Patients with the H/H genotype in the FCGR2A gene have higher survival rates when treated with cetuximab than do patients with the H/R and R/R genotypes, investigators reported.
In addition, polymorphism in the FCGR3A gene had no effect on survival.
“Only a proportion of patients with colorectal cancer receiving cetuximab derive benefit from the drug. However, other than RAS and BRAF mutations, no biomarkers have been identified as clinically useful predictors of response to cetuximab. Our primary objective was to determine whether survival is affected by a significant interaction between FCGR polymorphism and cetuximab treatment after adjusting for other potential prognostic factors,” wrote Dr. Geoffrey Liu of the University of Toronto and his associates (Clin Cancer Res. 2016 May 15;22:2435-44).
Cetuximab is a therapeutic monoclonal antibody that inhibits epidermal growth factor receptors by binding to their extracellular domain. Cetuximab also induces antibody-dependent cell cytotoxicity and promotes the endocytic and phagocytic activity in immune cells by binding to the Fc-gamma receptor (FCGR) of host effector cells. FCGR has a genetic polymorphism in the coding region of the FCGR2A gene that causes an amino acid change from histidine (H) to arginine (R). FCGR also has a genetic polymorphism in the coding region of the FCGR3A gene that causes an amino acid change from phenylalinine (F) to valine (V).
Dr. Liu and associates collected patient demographic information and clinical outcome data (overall survival and progression-free survival) from the NCIC CTG CO.17 database and tumor tissue samples from the NCIC CTG central tumor bank. DNA was genotyped blindly. From an original cohort of 572 patients with colorectal cancer, 286 patients had usable FCGR2A genetic data, and 288 patients had usable FCGR3A genetic data. Genetic polymorphisms were not associated with age, sex, performance status, disease site, prior therapies, and site/number of metastatic sites.
In Cox proportional hazard models controlling for clinically relevant factors, patients with the H/H genotype (HR, 7.95; 95% CI, 5.2-10.6) had greater survival benefits than patients with the H/R (HR, 6.6; 95% CI, 5.0-9.1) or R/R (HR, 6.34; 95% CI, 4.5-9.1) genotypes when treated with cetuximab (P = .01). There were no significant relationships between overall or progression-free survival and FCGR3A polymorphisms.
“This prognostic observation should be replicated in other colorectal cancer populations and possibly in other cancers, such as breast cancer or lymphoma, before being generalized into other settings,” the investigators wrote.
On Twitter @jess_craig94
FROM CLINICAL CANCER RESEARCH
Key clinical point: Patients with the H/H genotype in the FCGR2A gene have higher survival rates when treated with cetuximab than do patients with the H/R and R/R genotypes. Polymorphism in the FCGR3A gene has no effect on survival.
Major finding: Patients with the FCGR2A H/H genotype (HR, 7.95; 95% CI, 5.2-10.6) had greater survival benefits than patients with the H/R (HR, 6.6; 95% CI, 5.0-9.1) or R/R (HR, 6.34; 95% CI, 4.5-9.1) genotypes when treated with cetuximab (P = .01).
Data source: A retrospective, secondary analysis of genetic data for 572 patients with colorectal cancer. Data were originally collected during the NCIC CTG CO.17 multicenter, randomized, open-label phase III clinical trial.
Disclosures: This study was supported by an OICR High Impact Clinical Trial Small Project grant as well as grants and other financial support from Transgenomic, the Alan B. Brown Chair in Molecular Genomics, the Cancer Care Ontario chair in experimental therapeutics and population studies, and the Peter MacCallum Cancer Centre Research Foundation. Three investigators reported holding consulting or advisory board roles for AMGEN and/or Merck. One investigator reported receiving commercial research grants from Merck Serono. No other disclosures were reported by the other investigators.
