AVAHO

Timing of a switch to treatment from gefitinib to osimertinib based on molecular progression led to an earlier switch than timing based on conventional measures in a new study of 100 adults with epidermal growth factor (EGFR)–mutant non–small cell lung cancer (NSCLC).

Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).

However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.

The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.

The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.

The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.

Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.

More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.

As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.

The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.

In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.

The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.

Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”

The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.

Timing of a switch to treatment from gefitinib to osimertinib based on molecular progression led to an earlier switch than timing based on conventional measures in a new study of 100 adults with epidermal growth factor (EGFR)–mutant non–small cell lung cancer (NSCLC).

Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).

However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.

The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.

The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.

The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.

Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.

More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.

As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.

The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.

In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.

The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.

Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”

The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.

Timing of a switch to treatment from gefitinib to osimertinib based on molecular progression led to an earlier switch than timing based on conventional measures in a new study of 100 adults with epidermal growth factor (EGFR)–mutant non–small cell lung cancer (NSCLC).

Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).

However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.

The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.

The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.

The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.

Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.

More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.

As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.

The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.

In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.

The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.

Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”

The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.

The immunotherapy blinatumomab improves short-term outcomes when added to standard chemotherapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL), according to a report in the New England Journal of Medicine.

Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.

“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.

“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.

The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
 

Pediatric community responds

There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”

Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”

The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.

Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”

The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
 

Study details

Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.

The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m² per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.

Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.

Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.

There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.

There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.

Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.

The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.

The immunotherapy blinatumomab improves short-term outcomes when added to standard chemotherapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL), according to a report in the New England Journal of Medicine.

Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.

“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.

“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.

The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
 

Pediatric community responds

There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”

Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”

The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.

Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”

The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
 

Study details

Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.

The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m² per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.

Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.

Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.

There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.

There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.

Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.

The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.

The immunotherapy blinatumomab improves short-term outcomes when added to standard chemotherapy for infants with KMT2A-rearranged acute lymphoblastic leukemia (ALL), according to a report in the New England Journal of Medicine.

Two-year disease-free and overall survival measures, as well as the percentage of children who had complete minimal residual disease (MRD) responses, were substantially higher among the 30 infants in the study than in historical controls treated with the same chemotherapy backbone in an earlier trial, Interfant-06.

“These outcome data are very promising, given the poor survival and lack of improvements in outcomes among infants with KMT2A-rearranged ALL in recent decades,” said the investigators, led by Inge M. van der Sluis, MD, PhD, a hematologist-oncologist at Princess Maxima Center for Pediatric Oncology in Utrecht, the Netherlands.

“The low incidence of relapse after treatment with blinatumomab is remarkable, given that in historical controls relapses occur frequently and early during therapy,” the investigators stated. Although the “follow-up time was relatively short” in the study, “it included the period historically defined” as being at high risk of relapse, they said.

The team suggested that future research should assess whether infants benefit from multiple courses of blinatumomab, rather than the one course used in the study, and whether blinatumomab plus chemotherapy can replace stem cell transplants for high-risk infants.
 

Pediatric community responds

There was excitement on Twitter about the results; a number of pediatric blood cancer specialists were impressed and posted the study on that platform. Comments included, “Wow! After years of stagnation, a huge step forward for infant leukemia” and “great news for infant lymphoblastic leukemia.”

Akshay Sharma, MBBS, a pediatric bone marrow transplant and cellular therapy specialist at St. Jude Children’s Research Hospital, Memphis, also posted. He said in an interview that the findings are “very exciting.”

The “outcomes of children diagnosed with leukemia in their infancy, particularly if they have a KMT2A rearrangement, have been dismal. This is terrific progress and a testament to the role that immunotherapy and novel agents will be playing in treatment of several malignant diseases in the decade to come,” he said.

Another poster, Pratik “Tik” Patel, MD, a pediatric hematology/oncology fellow at Emory University in Atlanta, told this news organization that the study “is welcome news to pediatric oncologists” and highlights “the success in incorporating newer immune-based therapeutics upfront in treatment rather than in relapsed/refractory settings.”

The National Cancer Institute–funded Children’s Oncology Group is thinking the same way. The group is launching a large, randomized trial to test if adding blinatumomab to chemotherapy upfront for B-cell acute lymphoblastic leukemia and lymphoblastic lymphoma improves outcomes in children and young adults aged 1-31 years. Results are due after 2029.
 

Study details

Blinatumomab is an expensive “T-cell engager” that helps cytotoxic CD3+T cells link to and destroy leukemic CD19+ B cells. Past studies have shown that it’s safe and works in older children and adults with B-lineage ALL after intensive chemotherapy, but until now the approach hadn’t been tested in infants, the investigators said.

The 30 subjects in the study were under a year old and newly diagnosed with KMT2A-rearranged ALL. They were treated with the Interfant-06 chemotherapy regimen – cytosine arabinoside and other agents – plus one postinduction course of blinatumomab at 15 micrograms/m² per day as a 4-week continuous infusion. Eight of nine high-risk patients had allogeneic hematopoietic stem cell transplants.

Overall survival was 93.3% over a median follow up of 26.3 months, substantially higher than the 65.8% in the Interfant-06 trial. Two-year disease-free survival was 81.6% versus 49.4% in Interfant-06.

Sixteen patients (53%) were MRD negative after blinatumomab infusion and 12 (40%) had low levels of MRD. All of the children who continued chemotherapy went on to become MRD negative.

There were no permanent blinatumomab discontinuations and no treatment related deaths. Serious toxic effects were consistent with those in older patients and included four fevers, four infections, and one case each of hypertension and vomiting.

There were no cases of severe cytokine release syndrome (CRS) because of the low tumor burden of the subjects. Likewise, there were no obvious neurologic adverse events – like CRS, a particular concern with blinatumomab – but “we cannot rule out underreporting of mild neurologic symptoms that may have been unrecognized in infants,” the investigators said.

Patients who relapsed in the study had CNS involvement at relapse. “This underscores the need for adequate intrathecal chemotherapy during the blinatumomab infusion, because the efficacy of blinatumomab for the treatment of CNS leukemia may be limited,” they said.

The work was supported by Amgen, the maker of blinatumomab, as well as the Princess Maxima Center Foundation, the Danish Childhood Cancer Foundation, and others. Dr. Sluis is a consultant and researcher for Amgen. Five other authors were also consultants/advisers/researchers for the company. Dr. Sharma and Dr. Patel didn’t have any relevant disclosures.

The American Society of Clinical Oncology has released updated guidelines for treating anxiety and depression in adult cancer survivors.

Since the last guidelines, published in 2014, screening and assessment for depression and anxiety have improved, and a large new evidence base has emerged. To ensure the most up-to-date recommendations, a group of experts spanning psychology, psychiatry, medical and surgical oncology, internal medicine, and nursing convened to review the current literature on managing depression and anxiety. The review included 61 studies – 16 meta-analyses, 44 randomized controlled trials, and one systematic review – published between 2013 and 2021.

“The purpose of this guideline update is to gather and examine the evidence published since the 2014 guideline ... [with a] focus on management and treatment only.” The overall goal is to provide “the most effective and least resource-intensive intervention based on symptom severity” for patients with cancer, the experts write.

The new clinical practice guideline addresses the following question: What are the recommended treatment approaches in the management of anxiety and/or depression in survivors of adult cancer?

After an extensive literature search and analysis, the study was published online in the Journal of Clinical Oncology.

The expert panel’s recommendations fell into three broad categories – general management principles, treatment and care options for depressive symptoms, and treatment and care options for anxiety symptoms – with the guidelines for managing depression and anxiety largely mirroring each other.

The authors caution, however, that the guidelines “were developed in the context of mental health care being available and may not be applicable within other resource settings.”
 

General management principals

All patients with cancer, along with their caregivers, family members, or trusted confidants, should be offered information and resources on depression and anxiety. The panel gave this a “strong” recommendation but provided the caveat that the “information should be culturally informed and linguistically appropriate and can include a conversation between clinician and patient.”

Clinicians should select the most effective and least intensive intervention based on symptom severity when selecting treatment – what the panelists referred to as a stepped-care model. History of psychiatric diagnoses or substance use as well as prior responses to mental health treatment are some of the factors that may inform treatment choice.

For patients experiencing both depression and anxiety symptoms, treatment of depressive symptoms should be prioritized.

When referring a patient for further evaluation or care, clinicians “should make every effort to reduce barriers and facilitate patient follow-through,” the authors write. And health care professionals should regularly assess the treatment responses for patients receiving psychological or pharmacological interventions.

Overall, the treatments should be “supervised by a psychiatrist, and primary care or oncology providers work collaboratively with a nurse care manager to provide psychological interventions and monitor treatment compliance and outcomes,” the panelists write. “This type of collaborative care is found to be superior to usual care and is more cost-effective than face-to-face and pharmacologic treatment for depression.”
 

Treatment and care options for depressive and anxiety symptoms

For patients with moderate to severe depression symptoms, the panelists again stressed that clinicians should provide “culturally informed and linguistically appropriate information.” This information may include the frequency and symptoms of depression as well as signs these symptoms may be getting worse, with contact information for the medical team provided.

Among patients with moderate symptoms, clinicians can offer patients a range of individual or group therapy options, including cognitive-behavioral therapy (CBT), behavioral activation, mindfulness-based stress reduction, or structured physical activity and exercise. For patients with severe symptoms of depression, clinicians should offer individual therapy with one of these four treatment options: CBT, behavioral activation, mindfulness-based stress reduction, or interpersonal therapy.

The panelists offered almost identical recommendations for patients with anxiety, except mindfulness-based stress reduction was an option for patients with severe symptoms.

Clinicians can also provide pharmacologic options to treat depression or anxiety in certain patients, though the panelists provided the caveat that evidence for pharmacologic management is weak.

“These guidelines make no recommendations about any specific pharmacologic regimen being better than another,” the experts wrote. And “patients should be warned of potential harm or adverse effects.”

Overall, the panelists noted that, as highlighted in the 2014 ASCO guideline, the updated version continues to stress the importance of providing education on coping with stress, anxiety, and depression.

And “for individuals with elevated symptoms, validation and normalizing patients’ experiences is crucial,” the panelists write.

Although the timing of screening is not the focus of this updated review, the experts recognized that “how and when patients with cancer and survivors are screened are important determinants of timely management of anxiety and depression.”

And unlike the prior guideline, “pharmacotherapy is not recommended as a first-line treatment, neither alone nor in combination,” the authors say.

Overall, the panelists emphasize how widespread the mental health care crisis is and that problems accessing mental health care remain. “The choice of intervention to offer patients facing such obstacles should be based on shared decision-making, taking into account availability, accessibility, patient preference, likelihood of adverse events, adherence, and cost,” the experts conclude.

A version of this article first appeared on Medscape.com.

The American Society of Clinical Oncology has released updated guidelines for treating anxiety and depression in adult cancer survivors.

Since the last guidelines, published in 2014, screening and assessment for depression and anxiety have improved, and a large new evidence base has emerged. To ensure the most up-to-date recommendations, a group of experts spanning psychology, psychiatry, medical and surgical oncology, internal medicine, and nursing convened to review the current literature on managing depression and anxiety. The review included 61 studies – 16 meta-analyses, 44 randomized controlled trials, and one systematic review – published between 2013 and 2021.

“The purpose of this guideline update is to gather and examine the evidence published since the 2014 guideline ... [with a] focus on management and treatment only.” The overall goal is to provide “the most effective and least resource-intensive intervention based on symptom severity” for patients with cancer, the experts write.

The new clinical practice guideline addresses the following question: What are the recommended treatment approaches in the management of anxiety and/or depression in survivors of adult cancer?

After an extensive literature search and analysis, the study was published online in the Journal of Clinical Oncology.

The expert panel’s recommendations fell into three broad categories – general management principles, treatment and care options for depressive symptoms, and treatment and care options for anxiety symptoms – with the guidelines for managing depression and anxiety largely mirroring each other.

The authors caution, however, that the guidelines “were developed in the context of mental health care being available and may not be applicable within other resource settings.”
 

General management principals

All patients with cancer, along with their caregivers, family members, or trusted confidants, should be offered information and resources on depression and anxiety. The panel gave this a “strong” recommendation but provided the caveat that the “information should be culturally informed and linguistically appropriate and can include a conversation between clinician and patient.”

Clinicians should select the most effective and least intensive intervention based on symptom severity when selecting treatment – what the panelists referred to as a stepped-care model. History of psychiatric diagnoses or substance use as well as prior responses to mental health treatment are some of the factors that may inform treatment choice.

For patients experiencing both depression and anxiety symptoms, treatment of depressive symptoms should be prioritized.

When referring a patient for further evaluation or care, clinicians “should make every effort to reduce barriers and facilitate patient follow-through,” the authors write. And health care professionals should regularly assess the treatment responses for patients receiving psychological or pharmacological interventions.

Overall, the treatments should be “supervised by a psychiatrist, and primary care or oncology providers work collaboratively with a nurse care manager to provide psychological interventions and monitor treatment compliance and outcomes,” the panelists write. “This type of collaborative care is found to be superior to usual care and is more cost-effective than face-to-face and pharmacologic treatment for depression.”
 

Treatment and care options for depressive and anxiety symptoms

For patients with moderate to severe depression symptoms, the panelists again stressed that clinicians should provide “culturally informed and linguistically appropriate information.” This information may include the frequency and symptoms of depression as well as signs these symptoms may be getting worse, with contact information for the medical team provided.

Among patients with moderate symptoms, clinicians can offer patients a range of individual or group therapy options, including cognitive-behavioral therapy (CBT), behavioral activation, mindfulness-based stress reduction, or structured physical activity and exercise. For patients with severe symptoms of depression, clinicians should offer individual therapy with one of these four treatment options: CBT, behavioral activation, mindfulness-based stress reduction, or interpersonal therapy.

The panelists offered almost identical recommendations for patients with anxiety, except mindfulness-based stress reduction was an option for patients with severe symptoms.

Clinicians can also provide pharmacologic options to treat depression or anxiety in certain patients, though the panelists provided the caveat that evidence for pharmacologic management is weak.

“These guidelines make no recommendations about any specific pharmacologic regimen being better than another,” the experts wrote. And “patients should be warned of potential harm or adverse effects.”

Overall, the panelists noted that, as highlighted in the 2014 ASCO guideline, the updated version continues to stress the importance of providing education on coping with stress, anxiety, and depression.

And “for individuals with elevated symptoms, validation and normalizing patients’ experiences is crucial,” the panelists write.

Although the timing of screening is not the focus of this updated review, the experts recognized that “how and when patients with cancer and survivors are screened are important determinants of timely management of anxiety and depression.”

And unlike the prior guideline, “pharmacotherapy is not recommended as a first-line treatment, neither alone nor in combination,” the authors say.

Overall, the panelists emphasize how widespread the mental health care crisis is and that problems accessing mental health care remain. “The choice of intervention to offer patients facing such obstacles should be based on shared decision-making, taking into account availability, accessibility, patient preference, likelihood of adverse events, adherence, and cost,” the experts conclude.

A version of this article first appeared on Medscape.com.

The American Society of Clinical Oncology has released updated guidelines for treating anxiety and depression in adult cancer survivors.

Since the last guidelines, published in 2014, screening and assessment for depression and anxiety have improved, and a large new evidence base has emerged. To ensure the most up-to-date recommendations, a group of experts spanning psychology, psychiatry, medical and surgical oncology, internal medicine, and nursing convened to review the current literature on managing depression and anxiety. The review included 61 studies – 16 meta-analyses, 44 randomized controlled trials, and one systematic review – published between 2013 and 2021.

“The purpose of this guideline update is to gather and examine the evidence published since the 2014 guideline ... [with a] focus on management and treatment only.” The overall goal is to provide “the most effective and least resource-intensive intervention based on symptom severity” for patients with cancer, the experts write.

The new clinical practice guideline addresses the following question: What are the recommended treatment approaches in the management of anxiety and/or depression in survivors of adult cancer?

After an extensive literature search and analysis, the study was published online in the Journal of Clinical Oncology.

The expert panel’s recommendations fell into three broad categories – general management principles, treatment and care options for depressive symptoms, and treatment and care options for anxiety symptoms – with the guidelines for managing depression and anxiety largely mirroring each other.

The authors caution, however, that the guidelines “were developed in the context of mental health care being available and may not be applicable within other resource settings.”
 

General management principals

All patients with cancer, along with their caregivers, family members, or trusted confidants, should be offered information and resources on depression and anxiety. The panel gave this a “strong” recommendation but provided the caveat that the “information should be culturally informed and linguistically appropriate and can include a conversation between clinician and patient.”

Clinicians should select the most effective and least intensive intervention based on symptom severity when selecting treatment – what the panelists referred to as a stepped-care model. History of psychiatric diagnoses or substance use as well as prior responses to mental health treatment are some of the factors that may inform treatment choice.

For patients experiencing both depression and anxiety symptoms, treatment of depressive symptoms should be prioritized.

When referring a patient for further evaluation or care, clinicians “should make every effort to reduce barriers and facilitate patient follow-through,” the authors write. And health care professionals should regularly assess the treatment responses for patients receiving psychological or pharmacological interventions.

Overall, the treatments should be “supervised by a psychiatrist, and primary care or oncology providers work collaboratively with a nurse care manager to provide psychological interventions and monitor treatment compliance and outcomes,” the panelists write. “This type of collaborative care is found to be superior to usual care and is more cost-effective than face-to-face and pharmacologic treatment for depression.”
 

Treatment and care options for depressive and anxiety symptoms

For patients with moderate to severe depression symptoms, the panelists again stressed that clinicians should provide “culturally informed and linguistically appropriate information.” This information may include the frequency and symptoms of depression as well as signs these symptoms may be getting worse, with contact information for the medical team provided.

Among patients with moderate symptoms, clinicians can offer patients a range of individual or group therapy options, including cognitive-behavioral therapy (CBT), behavioral activation, mindfulness-based stress reduction, or structured physical activity and exercise. For patients with severe symptoms of depression, clinicians should offer individual therapy with one of these four treatment options: CBT, behavioral activation, mindfulness-based stress reduction, or interpersonal therapy.

The panelists offered almost identical recommendations for patients with anxiety, except mindfulness-based stress reduction was an option for patients with severe symptoms.

Clinicians can also provide pharmacologic options to treat depression or anxiety in certain patients, though the panelists provided the caveat that evidence for pharmacologic management is weak.

“These guidelines make no recommendations about any specific pharmacologic regimen being better than another,” the experts wrote. And “patients should be warned of potential harm or adverse effects.”

Overall, the panelists noted that, as highlighted in the 2014 ASCO guideline, the updated version continues to stress the importance of providing education on coping with stress, anxiety, and depression.

And “for individuals with elevated symptoms, validation and normalizing patients’ experiences is crucial,” the panelists write.

Although the timing of screening is not the focus of this updated review, the experts recognized that “how and when patients with cancer and survivors are screened are important determinants of timely management of anxiety and depression.”

And unlike the prior guideline, “pharmacotherapy is not recommended as a first-line treatment, neither alone nor in combination,” the authors say.

Overall, the panelists emphasize how widespread the mental health care crisis is and that problems accessing mental health care remain. “The choice of intervention to offer patients facing such obstacles should be based on shared decision-making, taking into account availability, accessibility, patient preference, likelihood of adverse events, adherence, and cost,” the experts conclude.

A version of this article first appeared on Medscape.com.

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

Adults with cancer experienced significant reductions in pain after taking medicinal cannabis, in a study.

Physician-prescribed cannabis, particularly cannabinoids, has been shown to ease cancer-related pain in adult cancer patients, who often find inadequate pain relief from medications including opioids, Saro Aprikian, MSc, a medical student at the Royal College of Surgeons, Dublin, and colleagues, wrote in their paper.

However, real-world data on the safety and effectiveness of cannabis in the cancer population and the impact on use of other medications are lacking, the researchers said.

In the study, published in BMJ Supportive & Palliative Care, the researchers reviewed data from 358 adults with cancer who were part of a multicenter cannabis registry in Canada between May 2015 and October 2018.

The average age of the patients was 57.6 years, and 48% were men. The top three cancer diagnoses in the study population were genitorurinary, breast, and colorectal.

Pain was the most common reason for obtaining a medical cannabis prescription, cited by 72.4% of patients.

Data were collected at follow-up visits conducted every 3 months over 1 year. Pain was assessed via the Brief Pain Inventory (BPI) and revised Edmonton Symptom Assessment System (ESAS-r) questionnaires and compared to baseline values. Patients rated their pain intensity on a sliding scale of 0 (none) to 10 (worst possible). Pain relief was rated on a scale of 0% (none) to 100% (complete).

Compared to baseline scores, patients showed significant decreases at 3, 6 and 9 months for BPI worst pain (5.5 at baseline, 3.6 for 3, 6, and 9 months) average pain (4.1 at baseline, 2.4, 2.3, and 2.7 for 3, 6, and 9 months, respectively), overall pain severity (2.7 at baseline, 2.3, 2.3, and 2.4 at 3, 6, and 9 months, respectively), and pain interference with daily life (4.3 at baseline, 2.4, 2.2, and 2.4 at 3, 6, and 9 months, respectively; P less than .01 for all four pain measures).

“Pain severity as reported in the ESAS-r decreased significantly at 3-month, 6-month and 9-month follow-ups,” the researchers noted.

In addition, total medication burden based on the medication quantification scale (MQS) and morphine equivalent daily dose (MEDD) were recorded at 3, 6, 9, and 12 months. MQS scores decreased compared to baseline at 3, 6, 9, and 12 months in 10%, 23.5%, 26.2%, and 31.6% of patients, respectively. Also compared with baseline, 11.1%, 31.3%, and 14.3% of patients reported decreases in MEDD scores at 3, 6, and 9 months, respectively.

Overall, products with equal amounts of active ingredients tetrahydrocannabinol (THC) and cannabidiol (CBD) were more effective than were those with a predominance of either THC or CBD, the researchers wrote.

Medical cannabis was well-tolerated; a total of 15 moderate to severe side effects were reported by 11 patients, 13 of which were minor. The most common side effects were sleepiness and fatigue, and five patients discontinued their medical cannabis because of side effects. The two serious side effects reported during the study period – pneumonia and a cardiovascular event – were deemed unlikely related to the patients’ medicinal cannabis use.

The findings were limited by several factors, including the observational design, which prevented conclusions about causality, the researchers noted. Other limitations included the loss of many patients to follow-up and incomplete data on other prescription medications in many cases.

The results support the use of medical cannabis by cancer patients as an adjunct pain relief strategy and a way to potentially reduce the use of other medications such as opioids, the authors concluded.

The study was supported by the Canadian Consortium for the Investigation of Cannabinoids, Collège des Médecins du Québec, and the Canopy Growth Corporation. The researchers had no financial conflicts to disclose.

NEW YORK – In a blood cancer conference session – “Will autologous stem cell transplant (ASCT) continue to be the standard of care (SoC) in frontline therapy for multiple myeloma (MM)?” – two experts weighed in on the merits of their approaches to treating MM at the Great Debates and Updates Hematologic Malignancies conference.

Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.

credit Dr. Landgren

A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy. 

Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.

“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.

In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.

“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.

He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.

“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.

courtesy of Dr. Richter

Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.

“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.

Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.

NEW YORK – In a blood cancer conference session – “Will autologous stem cell transplant (ASCT) continue to be the standard of care (SoC) in frontline therapy for multiple myeloma (MM)?” – two experts weighed in on the merits of their approaches to treating MM at the Great Debates and Updates Hematologic Malignancies conference.

Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.

credit Dr. Landgren

A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy. 

Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.

“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.

In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.

“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.

He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.

“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.

courtesy of Dr. Richter

Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.

“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.

Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.

NEW YORK – In a blood cancer conference session – “Will autologous stem cell transplant (ASCT) continue to be the standard of care (SoC) in frontline therapy for multiple myeloma (MM)?” – two experts weighed in on the merits of their approaches to treating MM at the Great Debates and Updates Hematologic Malignancies conference.

Hematologist-oncologists whose top priority is ensuring that patients have the best chance of progression-free survival (PFS) will continue to choose ASCT as a best practice, argued Amrita Krishnan, MD, hematologist at the Judy and Bernard Briskin Center for Multiple Myeloma Research, City of Hope Comprehensive Cancer Center, Duarte, Calif.

credit Dr. Landgren

A differing perspective was presented by C. Ola Landgren, MD, PhD, hematologist at the Sylvester Comprehensive Cancer Center at the University of Miami. Dr. Landgren cited evidence that, for newly diagnosed MM patients treated successfully with modern combination therapies, ASCT is not a mandatory treatment step before starting maintenance therapy. 

Making a case for ASCT as the SoC, Dr. Krishnan noted, “based on the DETERMINATION trial [DT], there is far superior rate of PFS with patients who get ASCT up front, compared patients who got only conventional chemotherapy with lenalidomide, bortezomib, and dexamethasone [RVd]. PFS is the endpoint we look for in our treatment regimens.

“If you don’t use ASCT up front, you may lose the opportunity at later relapse. This is not to say that transplant is the only tool at our disposal. It is just an indispensable one. The GRIFFIN trial [GT] has shown us that robust combinations of drugs [both RVd and dexamethasone +RVd] can improve patient outcomes both before and after ASCT,” Dr. Krishnan concluded.

In his presentation, Dr. Landgren stated that, in the DT, while PFS is prolonged by the addition of ASCT to RVd, adding ASCT did not significantly increase overall survival (OS) rates. He added that treatment-related AEs of grade 3+ occurred in only 78.2% of patients on RVd versus 94.2% of RVd + ASCT patients.

“ASCT should not be the SoC frontline treatment in MM because it does not prolong OS. The IFM trial and the DT both show that there is no difference in OS between drug combination therapy followed by transplant and maintenance versus combination therapy alone, followed by transplant and maintenance. Furthermore, patients who get ASCT have higher risk of developing secondary malignancies, worse quality of life, and higher long-term morbidity with other conditions,” Dr. Landgren said.

He cited the MAIA trial administered daratumumab and lenalidomide plus dexamethasone (DRd) to patients who were too old or too frail to qualify for ASCT. Over half of patients in the DRd arm of MAIA had an estimated progression-free survival rate at 60 months.

“Furthermore, GT and the MANHATTAN clinical trials showed that we can safely add CD38-targeted monoclonal antibodies to standard combination therapies [lenalidomide, bortezomib, and dexamethasone (KRd)], resulting in higher rates of minimal-residual-disease (MRD) negativity. That means modern four-drug combination therapies [DR-RVd and DR-KRd] will allow more [and more newly diagnosed] MM patients to achieve MRD negativity in the absence of ASCT,” Dr. Landgren concluded.

courtesy of Dr. Richter

Asked to comment on the two viewpoints, Joshua Richter, MD, director of myeloma treatment at the Blavatnik Family Center at Chelsea Mount Sinai, New York, said: “With some patients, we can get similar outcomes, whether or not we do a transplant. Doctors need to be better at choosing who really needs ASCT. Older people with standard-risk disease or people who achieve MRD-negative status after pharmacological treatment might not need to receive a transplant as much as those who have bulk disease or high-risk cytogenetics.

“Although ASCT might not be the best frontline option for everyone, collecting cells from most patients and storing them has many advantages. It allows us to do have the option of ASCT in later lines of therapy. In some patients with low blood counts, we can use stored cells to reboot their marrow and make them eligible for trials of promising new drugs,” Dr. Richter said.

Dr. Krishnan disclosed relationships with Takeda, Amgen, GlaxoSmithKline, Bristol-Myers Squibb, Sanofi, Pfizer, Adaptive, Regeneron, Janssen, AstraZeneca, Artiva, and Sutro. Dr. Landgren reported ties with Amgen, BMS, Celgene, Janssen, Takedam Glenmark, Juno, Pfizer, Merck, and others. Dr. Richter disclosed relationships with Janssen, BMS, and Takeda.

The U.S. government plans to no longer require federal workers or international air travelers to be vaccinated for COVID-19, the Biden administration has announced. 

The move means vaccines will no longer be required for workers who are federal employees, federal contractors, Head Start early education employees, workers at Medicare-certified health care facilities, and those who work at U.S. borders. International air travelers will no longer be required to prove their vaccination status. The requirement will be lifted at the end of the day on May 11, which is also when the federal public health emergency declaration ends.

“While vaccination remains one of the most important tools in advancing the health and safety of employees and promoting the efficiency of workplaces, we are now in a different phase of our response when these measures are no longer necessary,” an announcement from the White House stated.

White House officials credited vaccine requirements with saving millions of lives, noting that the rules ensured “the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations.”

More than 100 million people were subject to the vaccine requirement, The Associated Press reported. All but 2% of those covered by the mandate had received at least one dose or had a pending or approved exception on file by January 2022, the Biden administration said, noting that COVID deaths have dropped 95% since January 2021 and hospitalizations are down nearly 91%.

In January, vaccine requirements were lifted for U.S. military members.

On the government-run website Safer Federal Workforce, which helped affected organizations put federal COVID rules into place, agencies were told to “take no action to implement or enforce the COVID-19 vaccination requirement” at this time.

A version of this article first appeared on WebMD.com.

The U.S. government plans to no longer require federal workers or international air travelers to be vaccinated for COVID-19, the Biden administration has announced. 

The move means vaccines will no longer be required for workers who are federal employees, federal contractors, Head Start early education employees, workers at Medicare-certified health care facilities, and those who work at U.S. borders. International air travelers will no longer be required to prove their vaccination status. The requirement will be lifted at the end of the day on May 11, which is also when the federal public health emergency declaration ends.

“While vaccination remains one of the most important tools in advancing the health and safety of employees and promoting the efficiency of workplaces, we are now in a different phase of our response when these measures are no longer necessary,” an announcement from the White House stated.

White House officials credited vaccine requirements with saving millions of lives, noting that the rules ensured “the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations.”

More than 100 million people were subject to the vaccine requirement, The Associated Press reported. All but 2% of those covered by the mandate had received at least one dose or had a pending or approved exception on file by January 2022, the Biden administration said, noting that COVID deaths have dropped 95% since January 2021 and hospitalizations are down nearly 91%.

In January, vaccine requirements were lifted for U.S. military members.

On the government-run website Safer Federal Workforce, which helped affected organizations put federal COVID rules into place, agencies were told to “take no action to implement or enforce the COVID-19 vaccination requirement” at this time.

A version of this article first appeared on WebMD.com.

The U.S. government plans to no longer require federal workers or international air travelers to be vaccinated for COVID-19, the Biden administration has announced. 

The move means vaccines will no longer be required for workers who are federal employees, federal contractors, Head Start early education employees, workers at Medicare-certified health care facilities, and those who work at U.S. borders. International air travelers will no longer be required to prove their vaccination status. The requirement will be lifted at the end of the day on May 11, which is also when the federal public health emergency declaration ends.

“While vaccination remains one of the most important tools in advancing the health and safety of employees and promoting the efficiency of workplaces, we are now in a different phase of our response when these measures are no longer necessary,” an announcement from the White House stated.

White House officials credited vaccine requirements with saving millions of lives, noting that the rules ensured “the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations.”

More than 100 million people were subject to the vaccine requirement, The Associated Press reported. All but 2% of those covered by the mandate had received at least one dose or had a pending or approved exception on file by January 2022, the Biden administration said, noting that COVID deaths have dropped 95% since January 2021 and hospitalizations are down nearly 91%.

In January, vaccine requirements were lifted for U.S. military members.

On the government-run website Safer Federal Workforce, which helped affected organizations put federal COVID rules into place, agencies were told to “take no action to implement or enforce the COVID-19 vaccination requirement” at this time.

A version of this article first appeared on WebMD.com.

Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do. 

In an article published in Cell, cancer specialists from across the globe provided their take on the big questions worth exploring in research over the coming years.

More sex-specific research

Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.

Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.

“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said. 
 

The global cancer community

C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.

“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”

Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”

Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.

“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
 

Prioritizing combination therapies

The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.

“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”

A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma. 

“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
 

Cancer drugs and the heart

Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”

But, Dr. Moslehi explained, “we are entering [uncharted] waters.”

Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.

“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
 

Inside rare cancers

William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.

After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.

Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers. 

“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said. 

The researchers reported numerous relationships with pharmaceutical companies.
 

A version of this article first appeared on Medscape.com.

Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do. 

In an article published in Cell, cancer specialists from across the globe provided their take on the big questions worth exploring in research over the coming years.

More sex-specific research

Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.

Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.

“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said. 
 

The global cancer community

C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.

“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”

Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”

Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.

“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
 

Prioritizing combination therapies

The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.

“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”

A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma. 

“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
 

Cancer drugs and the heart

Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”

But, Dr. Moslehi explained, “we are entering [uncharted] waters.”

Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.

“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
 

Inside rare cancers

William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.

After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.

Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers. 

“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said. 

The researchers reported numerous relationships with pharmaceutical companies.
 

A version of this article first appeared on Medscape.com.

Cancer research has made big strides over the past few decades, leading to better prevention efforts, improved treatment options, and longer survival. Despite the significant progress, there is still a lot of work to do. 

In an article published in Cell, cancer specialists from across the globe provided their take on the big questions worth exploring in research over the coming years.

More sex-specific research

Sherene Loi, MBBS, PhD, head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the MacCallum Cancer Centre in Melbourne, said there needs to be more research on the differences in immune-related adverse events and immune responses between the sexes.

Dr. Loi’s recent research in mouse models has revealed that immune checkpoint inhibitors can lead to reduced oocyte reserves, and if those insights are validated in humans, it could have big implications for women of childbearing age who may face premature menopause and infertility.

“It is astonishing to realize that very little research has been done to investigate the long-term reproductive or fertility consequences of new agents we investigate in the phase 3 setting and then prescribe routinely in the curative setting,” Dr. Loi said. 
 

The global cancer community

C. S. Pramesh, MMBS, MS, FRCS, director of Tata Memorial Hospital in Mumbai, India, said that cancer research should prioritize global experiences, instead of focusing so heavily on high-income countries such as the United States.

“With much of the cancer burden likely to fall on low- and middle-income countries, it seems incongruous that almost 90% of cancer research currently takes place in high-income countries,” Dr. Pramesh said. “Neither the discordance between the cancer burden and research funding in high-income countries nor the types of problems or solutions addressed in these countries are relevant to the majority of patients with cancer in the world.”

Bishal Gyawali, MD, PhD, has discussed a similar need to prioritize cancer care in low- and middle-income countries, what he has dubbed “cancer groundshot.”

Dr. Pramesh described a brainstorming session among colleagues with global cancer expertise in which they identified five broad themes especially relevant to a global community. These themes include reducing the burden of patients presenting with advanced disease as well as improving access, affordability, and outcomes through solution-oriented research – goals that are critical but often not prioritized by high-income countries or industry, he said.

“Now is the time for the global community to wake up, take notice, and change the direction of cancer research for the larger public good,” Dr. Pramesh said.
 

Prioritizing combination therapies

The next big focus in cancer research should be to develop effective combination therapies, according to René Bernards, PhD, of The Netherlands Cancer Institute.

“Resistance to therapy remains a major obstacle in the treatment of cancer,” Dr. Bernards said. But, as the AIDS pandemic has taught us, the use of multiple drugs with “nonoverlapping resistance mechanisms can make a deadly disease with a high mutation rate chronic.”

A growing body of evidence highlights the relevance of this strategy to oncology. A recent study, for instance, highlighted the effectiveness of dual immune checkpoint inhibitors to treat advanced melanoma. 

“I believe that academic researchers can deliver more clinical benefit to patients by focusing on finding highly effective combinations of existing drugs than by searching for more drug targets,” he said. “Over time, this would also contribute to affordable health care through use of more generic drugs.”
 

Cancer drugs and the heart

Cardiologist Javid Moslehi, MD, who specializes in the cardiovascular health of patients with cancer, believes cardio-oncology should be the next frontier. During his research fellowship, Dr. Moslehi discovered that “many novel cancer therapies were leading to cardiovascular adverse effects, both during treatment and survivorship.”

But, Dr. Moslehi explained, “we are entering [uncharted] waters.”

Patients who receive immune checkpoint inhibitors may, for instance, develop fulminant myocarditis. Dr. Moslehi and colleagues have also found in preclinical models that abatacept (CTLA4-Ig) may be an effective treatment for myocarditis.

“Because of the targeted nature of new cancer therapies, cardiovascular sequelae may provide insights into cardiac biology, making cardio-oncology a novel platform for cardiovascular investigation,” Dr. Moslehi explained.
 

Inside rare cancers

William Sellers, MD, director of the Broad Institute of MIT’s Cancer Program, Cambridge, Mass., said rare cancers should be the next focus.

After all, “rare cancers are only rare in isolation,” Dr. Sellers said, noting that these cancers make up 20%-24% of all cancer diagnoses.

Although funding for rare cancer research remains limited, investing more could benefit patients in the long run. In early 2023, Pfizer announced plans to explore more options for early stage treatments for rare diseases and cancers. 

“New initiatives supporting direct-to-patient cohort enrollment bridging geographic fragmentation and rare cancer model development, enabling preclinical research to accelerate, are the first steps along a path toward curing these diseases,” he said. 

The researchers reported numerous relationships with pharmaceutical companies.
 

A version of this article first appeared on Medscape.com.

An old dog – nitrous oxide – can learn new tricks, managing pain in men undergoing transrectal biopsies, researchers reported at the annual meeting of the American Urological Association.

“At concentrations of less than 50%, nitrous oxide is classified as a minimal sedative, making it a promising option for many urologic outpatient procedures such as prostate biopsies,” said Heidi Rayala, MD, PhD, assistant professor of surgery at Harvard Medical School, Boston, who helped conduct the study.

Nitrous oxide is best known as a pain medication and anesthetic during dental procedures and childbirth, after trauma, and in end-of-life care.

In the new study, Dr. Rayala and her colleagues at Harvard and Beth Israel-Deaconess Medical Center, Boston, randomly assigned 128 men to self-administered nitrous oxide (SANO) or oxygen as a placebo. Patients in the SANO group had a smaller change in post-biopsy pain score (Visual Analog Scale for pain, 0.43 vs. 1.03; P = .03) and lower odds of experiencing pain during the procedure (odds ratio, 0.45; confidence interval, 0.21-0.97; P = .04).

A comparison of anxiety scores in the two groups failed to find a statistically significant difference between SANO and placebo. However, more men who received nitrous oxide said they tolerated the procedure “better than expected” (61% vs. 41%; P = 0.02), according to the researchers.

Dr. Rayala said that the researchers used the Nitrouseal system (Sedation Systems), in which the patient holds a mask to their face and works with staff to adjust the gas levels to the desired amount. The system is governed to max out at 50% nitrous oxide, ensuring “minimal sedation concentrations, so anesthesia personnel are not required,” she said.

“At levels of less than 50%, patients respond normally to verbal commands and maintain normal airway reflexes,” Dr. Rayala added. “This provides an advantage in that patients do not require the presence of anesthesia personnel.” And because the body eliminates the gas within about 5 minutes, patients do not require an escort home, she said.

This system is also self-scavenging to protect the operating urologist and other personnel from environmental exposure to nitrous oxide.

Dr. Rayala said that three patients (2.3%) found the mask uncomfortable, but in follow-up studies the clinicians have done a better job of preparing patients for the feeling of the mask, making a marked difference. Headaches and nausea are the most commonly reported complaints at concentrations above 50%.

“We did not have patients report headaches or nausea in new study (by the BIDMC group),” she said. This study has been submitted for publication.

Clinicians outside the United States have been quicker to embrace nitrous oxide for prostate procedures.

In a randomized controlled trial, researchers in Australia found no significant improvement in pain scores at 15 minutes from the use of nitrous oxide during transrectal biopsies; however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Stephen McCombie, MD, a consultant at Perth Urology Clinic, Australia, who has been adapting the nitrous oxide protocol for transrectal biopsies to transperineal procedures, said that the Beth Israel study “adds to the evidence to support adjunct use of mild inhalational anesthetics and analgesics during prostate biopsies to improve the patient experience of the procedure.”

He said that the role for these agents may grow with the global trend away from transrectal prostate biopsies and toward transperineal biopsies, largely driven by increasing rates of sepsis after transrectal biopsies.

“While transperineal biopsies can be more painful then transrectal biopsies when performed under local anesthesia, perhaps due to biopsies being taken through the highly sensate perineum as opposed to above the dentate line, optimization of the technique can significantly reduce the discomfort associated with the procedure, which may be further reduced with these agents,” Dr. McCombie said.

“Studies indicate that transperineal biopsies can be more painful than the traditional transrectal biopsies,” Dr. Rayala said. “We do offer transperineal biopsies at BIDMC, and we are gearing up to repeat the SANO study” for those patients.

Dr. Rayala and Dr. McCombie have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An old dog – nitrous oxide – can learn new tricks, managing pain in men undergoing transrectal biopsies, researchers reported at the annual meeting of the American Urological Association.

“At concentrations of less than 50%, nitrous oxide is classified as a minimal sedative, making it a promising option for many urologic outpatient procedures such as prostate biopsies,” said Heidi Rayala, MD, PhD, assistant professor of surgery at Harvard Medical School, Boston, who helped conduct the study.

Nitrous oxide is best known as a pain medication and anesthetic during dental procedures and childbirth, after trauma, and in end-of-life care.

In the new study, Dr. Rayala and her colleagues at Harvard and Beth Israel-Deaconess Medical Center, Boston, randomly assigned 128 men to self-administered nitrous oxide (SANO) or oxygen as a placebo. Patients in the SANO group had a smaller change in post-biopsy pain score (Visual Analog Scale for pain, 0.43 vs. 1.03; P = .03) and lower odds of experiencing pain during the procedure (odds ratio, 0.45; confidence interval, 0.21-0.97; P = .04).

A comparison of anxiety scores in the two groups failed to find a statistically significant difference between SANO and placebo. However, more men who received nitrous oxide said they tolerated the procedure “better than expected” (61% vs. 41%; P = 0.02), according to the researchers.

Dr. Rayala said that the researchers used the Nitrouseal system (Sedation Systems), in which the patient holds a mask to their face and works with staff to adjust the gas levels to the desired amount. The system is governed to max out at 50% nitrous oxide, ensuring “minimal sedation concentrations, so anesthesia personnel are not required,” she said.

“At levels of less than 50%, patients respond normally to verbal commands and maintain normal airway reflexes,” Dr. Rayala added. “This provides an advantage in that patients do not require the presence of anesthesia personnel.” And because the body eliminates the gas within about 5 minutes, patients do not require an escort home, she said.

This system is also self-scavenging to protect the operating urologist and other personnel from environmental exposure to nitrous oxide.

Dr. Rayala said that three patients (2.3%) found the mask uncomfortable, but in follow-up studies the clinicians have done a better job of preparing patients for the feeling of the mask, making a marked difference. Headaches and nausea are the most commonly reported complaints at concentrations above 50%.

“We did not have patients report headaches or nausea in new study (by the BIDMC group),” she said. This study has been submitted for publication.

Clinicians outside the United States have been quicker to embrace nitrous oxide for prostate procedures.

In a randomized controlled trial, researchers in Australia found no significant improvement in pain scores at 15 minutes from the use of nitrous oxide during transrectal biopsies; however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Stephen McCombie, MD, a consultant at Perth Urology Clinic, Australia, who has been adapting the nitrous oxide protocol for transrectal biopsies to transperineal procedures, said that the Beth Israel study “adds to the evidence to support adjunct use of mild inhalational anesthetics and analgesics during prostate biopsies to improve the patient experience of the procedure.”

He said that the role for these agents may grow with the global trend away from transrectal prostate biopsies and toward transperineal biopsies, largely driven by increasing rates of sepsis after transrectal biopsies.

“While transperineal biopsies can be more painful then transrectal biopsies when performed under local anesthesia, perhaps due to biopsies being taken through the highly sensate perineum as opposed to above the dentate line, optimization of the technique can significantly reduce the discomfort associated with the procedure, which may be further reduced with these agents,” Dr. McCombie said.

“Studies indicate that transperineal biopsies can be more painful than the traditional transrectal biopsies,” Dr. Rayala said. “We do offer transperineal biopsies at BIDMC, and we are gearing up to repeat the SANO study” for those patients.

Dr. Rayala and Dr. McCombie have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An old dog – nitrous oxide – can learn new tricks, managing pain in men undergoing transrectal biopsies, researchers reported at the annual meeting of the American Urological Association.

“At concentrations of less than 50%, nitrous oxide is classified as a minimal sedative, making it a promising option for many urologic outpatient procedures such as prostate biopsies,” said Heidi Rayala, MD, PhD, assistant professor of surgery at Harvard Medical School, Boston, who helped conduct the study.

Nitrous oxide is best known as a pain medication and anesthetic during dental procedures and childbirth, after trauma, and in end-of-life care.

In the new study, Dr. Rayala and her colleagues at Harvard and Beth Israel-Deaconess Medical Center, Boston, randomly assigned 128 men to self-administered nitrous oxide (SANO) or oxygen as a placebo. Patients in the SANO group had a smaller change in post-biopsy pain score (Visual Analog Scale for pain, 0.43 vs. 1.03; P = .03) and lower odds of experiencing pain during the procedure (odds ratio, 0.45; confidence interval, 0.21-0.97; P = .04).

A comparison of anxiety scores in the two groups failed to find a statistically significant difference between SANO and placebo. However, more men who received nitrous oxide said they tolerated the procedure “better than expected” (61% vs. 41%; P = 0.02), according to the researchers.

Dr. Rayala said that the researchers used the Nitrouseal system (Sedation Systems), in which the patient holds a mask to their face and works with staff to adjust the gas levels to the desired amount. The system is governed to max out at 50% nitrous oxide, ensuring “minimal sedation concentrations, so anesthesia personnel are not required,” she said.

“At levels of less than 50%, patients respond normally to verbal commands and maintain normal airway reflexes,” Dr. Rayala added. “This provides an advantage in that patients do not require the presence of anesthesia personnel.” And because the body eliminates the gas within about 5 minutes, patients do not require an escort home, she said.

This system is also self-scavenging to protect the operating urologist and other personnel from environmental exposure to nitrous oxide.

Dr. Rayala said that three patients (2.3%) found the mask uncomfortable, but in follow-up studies the clinicians have done a better job of preparing patients for the feeling of the mask, making a marked difference. Headaches and nausea are the most commonly reported complaints at concentrations above 50%.

“We did not have patients report headaches or nausea in new study (by the BIDMC group),” she said. This study has been submitted for publication.

Clinicians outside the United States have been quicker to embrace nitrous oxide for prostate procedures.

In a randomized controlled trial, researchers in Australia found no significant improvement in pain scores at 15 minutes from the use of nitrous oxide during transrectal biopsies; however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Stephen McCombie, MD, a consultant at Perth Urology Clinic, Australia, who has been adapting the nitrous oxide protocol for transrectal biopsies to transperineal procedures, said that the Beth Israel study “adds to the evidence to support adjunct use of mild inhalational anesthetics and analgesics during prostate biopsies to improve the patient experience of the procedure.”

He said that the role for these agents may grow with the global trend away from transrectal prostate biopsies and toward transperineal biopsies, largely driven by increasing rates of sepsis after transrectal biopsies.

“While transperineal biopsies can be more painful then transrectal biopsies when performed under local anesthesia, perhaps due to biopsies being taken through the highly sensate perineum as opposed to above the dentate line, optimization of the technique can significantly reduce the discomfort associated with the procedure, which may be further reduced with these agents,” Dr. McCombie said.

“Studies indicate that transperineal biopsies can be more painful than the traditional transrectal biopsies,” Dr. Rayala said. “We do offer transperineal biopsies at BIDMC, and we are gearing up to repeat the SANO study” for those patients.

Dr. Rayala and Dr. McCombie have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.

On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.

Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.

In reviewing the application, the FDA raised concerns about this broad new indication, highlighting limitations in the key research used to justify the expanded use and highlighting how olaparib may amount to a “toxic placebo,” a phrase agency staff used in their briefing document.

Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”

The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.

Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.

The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).

Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.

In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.

That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.

Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.

The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.

Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.

AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”

One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.

People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.

But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.

“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.

A version of this article first appeared on Medscape.com.

A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.

On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.

Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.

In reviewing the application, the FDA raised concerns about this broad new indication, highlighting limitations in the key research used to justify the expanded use and highlighting how olaparib may amount to a “toxic placebo,” a phrase agency staff used in their briefing document.

Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”

The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.

Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.

The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).

Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.

In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.

That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.

Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.

The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.

Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.

AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”

One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.

People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.

But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.

“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.

A version of this article first appeared on Medscape.com.

A panel of independent advisers recently almost unanimously recommended to restrict a new indication for olaparib (Lynparza) alongside abiraterone (Zytiga) in patients with metastatic castration-resistant prostate cancer.

On April 28, members of the Oncologic Drugs Advisory Committee voted 11 to 1, with one abstention, that only patients whose tumors have a BRCA mutation should receive olaparib as part of the combination first-line treatment for metastatic castration-resistant prostate cancer.

Olaparib is already cleared by the Food and Drug Administration for various ovarian, breast, and pancreatic cancer indications as well as later-line use in certain more advanced prostate cancers. AstraZeneca recently applied for an additional, broad indication for the poly (ADP-ribose) polymerase (PARP) inhibitor as an initial therapy that would include patients without BRCA or homologous recombination repair (HRR) mutations.

In reviewing the application, the FDA raised concerns about this broad new indication, highlighting limitations in the key research used to justify the expanded use and highlighting how olaparib may amount to a “toxic placebo,” a phrase agency staff used in their briefing document.

Given these concerns, the FDA reviewers asked the independent ODAC panel to vote on the following question: “As FDA reviews the proposed indication for olaparib in combination with abiraterone for initial treatment of [metastatic castration-resistant prostate cancer], should the indication be restricted to patients whose tumors have a BRCA mutation?”

The ODAC panel voted 11 to 1 in favor of a restricted expansion of olaparib plus abiraterone and prednisone or prednisolone to patients whose tumors have a BRCA mutation. One member – Ravi A. Madan, MD, of the National Cancer Institute – abstained. The FDA staff asked panelists to abstain if they felt the combination treatment should not be approved for any indication.

Overall, the ODAC panel agreed with the FDA staff’s criticism of the research supporting the application: the PROpel study. The trial randomized 796 patients with previously untreated metastatic castration-resistant prostate cancer to olaparib plus abiraterone or abiraterone plus placebo. The median time for radiographic progression-free survival – the study’s primary endpoint – was nearly 25 months in the olaparib group versus 16.6 months in the placebo group.

The combination also demonstrated a 19% reduced risk of death, which was not statistically significant (hazard ratio, 0.81; P = .0544), and a median improvement of 7.4 months in the combination arm (42.1 vs. 34.7 months).

Although the study met its primary endpoint, the results were difficult to interpret given the lack of information about genetic variability in the participants’ tumors. Participants were not prospectively assessed for either BRCA or HRR status. But given the importance of BRCA status as a predictive biomarker for PARP inhibitor efficacy, “this trial design would be considered inappropriate today as the biomarker should have been prospectively evaluated,” the FDA wrote in its briefing document.

In a post hoc analysis performed by the FDA, the agency found that BRCA-positive patients accounted for most of the survival benefit of the combination, though made up only 11% of the PROpel population.

That meant the ODAC members were being asked to evaluate a drug based on “suboptimal data” resulting from a “suboptimal study design,” said Dr. Madan, who is head of the prostate cancer clinical research section in the NCI’s Center for Cancer Research.

Dr. Madan also emphasized concerns the FDA raised about the potential harms for patients whose prostate cancer was not tied to BRCA mutations. In the FDA’s briefing document, the agency said patients treated in the first-line metastatic castration-resistant prostate cancer setting generally have few symptoms at baseline. Adding olaparib among patients lacking the BRCA mutation could expose them to a drug with known side effects but minimal chance to help them.

The PROpel trial also found that patients who received olaparib and abiraterone experienced greater toxicity than those who received abiraterone. These adverse events included venous thromboembolic events, myelosuppression, requirement for blood transfusions, nausea, vomiting, and diarrhea.

Although the FDA is not compelled to follow the recommendations of its advisory committees, it often does.

AstraZeneca expressed some disappointment about the recommendation in a press release. Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said, “while we are pleased with the recognition of the benefit of Lynparza plus abiraterone for patients with BRCA-mutated metastatic castration-resistant prostate cancer, we are disappointed with the outcome of today’s ODAC meeting. We strongly believe in the results of the PROpel trial, which demonstrated the clinically meaningful benefit for this combination in a broad population of patients regardless of biomarker status.”

One ODAC member, Jorge J. Nieva, MD, did support the expanded approval for olaparib, casting the single “no” vote. Dr. Nieva, an oncologist at the University of Southern California, Los Angeles, disagreed with the FDA’s question about limiting use of the olaparib-abiraterone combination to patients with known BRCA mutations, citing the positive result from the PROpel trial.

People are aware that olaparib provides a great deal more benefit in the BRCA-positive group and may give “only minimal benefit if these tests are not positive,” but “these risks and benefits can be addressed at the patient and physician level,” he said.

But Terrence M. Kungel, MBA, who served as ODAC’s patient representative for the meeting, offered a counterpoint to Dr. Nieva’s assessment. Patients now often struggle to assess the options available to them and then pay for these medicines, with financial toxicity affecting many people with cancer.

“Prostate cancer patients need more treatments that are effective, not more choices,” said Mr. Kungel, who voted with the majority.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.

There is one situation, while not common, that is often among the most difficult for me: the person who must be told at diagnosis that they are already dying. I am still reminded of a patient I saw early in my career.

A woman in her 40s was admitted to the hospital complaining of severe shortness of breath. In retrospect, she had been sick for months. She had not sought help because she was young and thought it would pass – the results of a “bad bug” that she just couldn’t shake.

But in the past few weeks, the persistence of symptoms became associated with weight loss, profound fatigue, loss of appetite, and nausea.

By the time she was hospitalized she was emaciated, though she appeared pregnant – a sign of the fluid that had built up in her abdomen. Imaging showed that her abdomen was filled with disease (carcinomatosis) and her liver and lungs were nearly replaced with metastatic disease.

A biopsy revealed an aggressive cancer that had no identifying histologic marker: carcinoma, not otherwise specified, or cancer of unknown primary.

I still remember seeing her. She had a deer-in-headlights stare that held me as I approached. I introduced myself and sat down so we were eye to eye.

“Tell me what you know,” I said.

“I know I have cancer and they don’t know where it started. I know surgery is not an option and that’s why they’ve asked you to come. Whatever. I’m ready. I want to fight this because I know I can beat it,” she said.

I remember that she looked very sick; her thin face and arms contrasted with her large, distended abdomen. Her breathing was labored, her skin almost gray. For a moment I didn’t know what to say.

As doctors, we like to believe that our decisions are guided by data: the randomized trials and meta-analyses that set standards of care; phase 2 trials that establish evidence (or lack thereof) of activity; case-control studies that suggest the impacts of treatment; and at the very least, case studies that document that “N of 1” experience. We have expert panels and pathways that lay out what treatments we should be using to help ensure access to quality care in every clinic on every corner of every cancer center in the United States.

These data and pathways tell us objectively what we can expect from therapy, who is at most risk for toxicities, and profiles of patients for whom treatment is not likely to be of benefit. In an ideal world, this objectivity would help us help people decide on an approach. But life is not objective, and sometimes individualizing care is as important as data.

In this scenario, I knew only one thing: She was dying. She had an overwhelming tumor burden. But I still asked myself a question that many in, and outside of, oncology ask themselves: Could she be saved?

This question was made even more difficult because she was young. She had her whole life ahead of her. It seemed incongruous that she would be here now, facing the gravity of her situation.

Looking at her, I saw the person, not a data point in a trial or a statistic in a textbook. She was terrified. And she was not ready to die.

I sat down and reviewed what I knew about her cancer and what I did not know. I went through potential treatments we could try and the toxicities associated with each. I made clear that these treatments, based on how sick she was, could kill her.

“Whatever we do,” I said, “you do not have disease that I can cure.”

She cried then, realizing what a horrible situation she was in and that she would no longer go back to her normal life. Indeed, she seemed to grasp that she was probably facing the end of her life and that it could be short.

“My concern is,” I continued, “that treatment could do the exact opposite of what I hope it would do. It could kill you sooner than this cancer will.”

Instead of making a treatment plan, I decided that it would be best to come back another day, so I said my goodbyes and left. Still, I could not stop thinking about her and what I should suggest as her next steps. My heart wanted to try treatment, give her a chance, even if it killed her. But my brain told me that treatment is not likely to work and may make her life even shorter.

I asked colleagues what they would suggest. Some recommended hospice care, others recommended treatment. Clearly, there was no one way to proceed.

One might wonder: Why is it so hard to do the right thing?

Ask any clinician and I think you will hear the same answer: Because we do not have the luxury of certainty.

Am I certain that this person will not benefit from intubation? Am I certain that she has only weeks to live? Am I sure that there are no treatments that will work?

The answer to these questions is no – I am not certain. It is that uncertainty that always makes me pause because it reminds me of my own humanity.

I stopped by the next day to see her surrounded by family. After some pleasantries I took the opportunity to reiterate much of our conversation from the other day. After some questions, I looked at her and asked if she wanted to talk more about her options. I was prepared to suggest treatment, anticipating that she would want it. Instead, she told me she didn’t want to proceed.

“I feel like I’m dying, and if what you have to give me isn’t going to cure me, then I’d prefer not to suffer while it happens. You said it’s up to me. I don’t want it.”

First, do no harm. It’s one of the tenets of medicine – to provide care that will benefit the people who have trusted us with their lives, whether that be longevity, relief of symptoms, or helping them achieve their last wishes. Throughout one’s life, goals might change but that edict remains the same.

But that can be difficult, especially in oncology and especially when one is not prepared for their own end of life. It can be hard for doctors to discuss the end of life; it’s easier to focus on the next treatment, instilling hope that there’s more that can be done. And there are people with end-stage cancer who insist on continuing treatment in the same circumstances, preferring to “die fighting” than to “give up.” Involving supportive and palliative care specialists early has helped in both situations, which is certainly a good thing.

We talked a while more and then arranged for our palliative care team to see her. I wish I could say I was at peace with her decision, but I wasn’t. The truth is, whatever she decided would probably have the same impact: I wouldn’t be able to stop thinking about it.

Dr. Dizon is professor of medicine, department of medicine, at Brown University and director of medical oncology at Rhode Island Hospital, both in Providence, R.I. He disclosed conflicts of interest with Regeneron, AstraZeneca, Clovis, Bristol Myers Squibb, and Kazia.

A version of this article first appeared on Medscape.com.