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Anticlaudin antibody increases survival in advanced gastric cancer
CHICAGO – The novel antibody IMAB362 extended survival of patients with advanced gastric cancer when added to chemotherapy, according to a phase II trial presented at the annual meeting of the Society of Clinical Oncology.
IMAB362 is a first-in-class monoclonal antibody targeting claudin18.2, a protein component of cellular tight junctions abundant in gastric tumors, as well as tumors of the pancreas, lung, esophagus, and ovaries.
IMAB362 significantly extended median overall survival (OS) when added to standard chemotherapy (13.2 vs. 8.4 months, hazard ratio [HR] = 0.51, P = .0001). Patients with the highest levels of claudin18.2 had an even longer median overall survival (16.7 vs. 9.0 months, HR = 0.45, P less than .0005).
The FAST (Phase II First-Line Therapy in Patients With Advanced CLDN18.2+ Gastric and Gastroesophageal Junction Adenocarcinoma) trial included patients who had no prior chemotherapy for locally advanced or metastatic disease. Tumors had to have 2+/3+ CLDN18.2 expression in 40% or more of tumor cells, and patients had an Eastern Cooperative Oncology Group performance status of 0-1.
Patients with tumors that expressed higher levels of claudin18,2, the target antigen, did better than the overall cohort in terms of progression-free survival (PFS), the primary endpoint.
“The FAST trial clearly met its primary endpoint, and there is a significant improvement in PFS and OS in the entire cohort and also in the higher expressers,” lead author Dr. Salah-Eddin Al-Batran, medical director of the Institute of Clinical Cancer Research, Nordwest Hospital in Frankfurst am Main, Germany, said in a news conference at the meeting.
The IMAB362 monoclonal antibody is highly specific for CLDN18.2 and works through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In combination with chemotherapy, by binding to tumor debris, it is an immunomodulator of the tumor microenvironment.
About 50% of gastric tumors express CLDN18.2. After screening, the investigators randomized 246 patients to three treatment arms: epirubicin/oxaliplatin/capecitabine (EOX), n = 84; EOX + IMAB362 at a loading dose of 800 mg/m2, then 600 mg/m2 on day 1 every 3 weeks, n = 77; or a higher dose of IMAB362 with EOX, n = 85. Dr. Al-Batran reported results of the first two arms and will present results for the third arm at a later time.
Median progression-free survival was 4.8 months with EOX and 7.9 months with EOX plus IMAB362 (HR = .47; P = .0001).
If 70% or more of the tumor cells expressed CLDN18.2, IMAB362 improved the median PFS from 5.6 months for EOX alone to 7.2 months (HR = 0.36, P less than .0005), and OS improved from 9 months to 16.7 months (HR = 0.45, P less than .0005).
Response rates were also better with the addition of IMAB362. The objective response rate by RECIST criteria was 39.0% with EOX + IMAB362 vs. 25.0% with EOX alone. Most of the responses were partial (28.6% vs. 21.4%, respectively) or stable disease (44.2% vs. 51.2%, respectively). There were only 10.4% complete responses with IMAB362 and 3.6% with EOX alone. About 12% of the patients in each arm were not evaluable, or the data were missing.
Both treatments were well tolerated, with most adverse effects being grade 1/2. However, there was more grade 3/4 neutropenia with the combination (32.5% vs. 21.4% for EOX alone) as well as grade 3/4 vomiting (10.4% vs. 3.6%, respectively). Grade 1/2 vomiting was common in both arms, with about one-third of patients receiving EOX alone and just over half of patients on EOX + IMAB362 being affected.
Dr. Al-Batran said that there may have been more vomiting with IMAB362 because tight junction proteins, including claudin, are present in the gastric mucosa. Diarrhea was largely grade 1/2, affected about one-third of patients receiving EOX alone, and was only about half as common among patients receiving the combination.
Dr. Al-Batran said this trial “provides a strong rationale for a confirmatory phase III trial.”
Press conference moderator Dr. Smitha Krishnamurthi said the study is important because it documents the activity of a first-in-class antibody in patients with advanced gastric and gastroesophageal junction cancers. Since CLDN18.2 is expressed in about 50% of these cancers, “this treatment could apply to many patients,” she said.
The study was initiated and sponsored by Ganymed Pharmaceuticals. Dr. Al-Batran has had a consulting or advisory role with Merck, Roche, Celgene, and Lilly; has been on the speakers bureau of Lilly, Roche, Celgene, and Nordic Bioscience; and has received research funding from Celgene, Roche Pharma, Lilly, Novartis, Vfor Pharma, Medac, and Hospira.
On Twitter @OncologyPractic
CHICAGO – The novel antibody IMAB362 extended survival of patients with advanced gastric cancer when added to chemotherapy, according to a phase II trial presented at the annual meeting of the Society of Clinical Oncology.
IMAB362 is a first-in-class monoclonal antibody targeting claudin18.2, a protein component of cellular tight junctions abundant in gastric tumors, as well as tumors of the pancreas, lung, esophagus, and ovaries.
IMAB362 significantly extended median overall survival (OS) when added to standard chemotherapy (13.2 vs. 8.4 months, hazard ratio [HR] = 0.51, P = .0001). Patients with the highest levels of claudin18.2 had an even longer median overall survival (16.7 vs. 9.0 months, HR = 0.45, P less than .0005).
The FAST (Phase II First-Line Therapy in Patients With Advanced CLDN18.2+ Gastric and Gastroesophageal Junction Adenocarcinoma) trial included patients who had no prior chemotherapy for locally advanced or metastatic disease. Tumors had to have 2+/3+ CLDN18.2 expression in 40% or more of tumor cells, and patients had an Eastern Cooperative Oncology Group performance status of 0-1.
Patients with tumors that expressed higher levels of claudin18,2, the target antigen, did better than the overall cohort in terms of progression-free survival (PFS), the primary endpoint.
“The FAST trial clearly met its primary endpoint, and there is a significant improvement in PFS and OS in the entire cohort and also in the higher expressers,” lead author Dr. Salah-Eddin Al-Batran, medical director of the Institute of Clinical Cancer Research, Nordwest Hospital in Frankfurst am Main, Germany, said in a news conference at the meeting.
The IMAB362 monoclonal antibody is highly specific for CLDN18.2 and works through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In combination with chemotherapy, by binding to tumor debris, it is an immunomodulator of the tumor microenvironment.
About 50% of gastric tumors express CLDN18.2. After screening, the investigators randomized 246 patients to three treatment arms: epirubicin/oxaliplatin/capecitabine (EOX), n = 84; EOX + IMAB362 at a loading dose of 800 mg/m2, then 600 mg/m2 on day 1 every 3 weeks, n = 77; or a higher dose of IMAB362 with EOX, n = 85. Dr. Al-Batran reported results of the first two arms and will present results for the third arm at a later time.
Median progression-free survival was 4.8 months with EOX and 7.9 months with EOX plus IMAB362 (HR = .47; P = .0001).
If 70% or more of the tumor cells expressed CLDN18.2, IMAB362 improved the median PFS from 5.6 months for EOX alone to 7.2 months (HR = 0.36, P less than .0005), and OS improved from 9 months to 16.7 months (HR = 0.45, P less than .0005).
Response rates were also better with the addition of IMAB362. The objective response rate by RECIST criteria was 39.0% with EOX + IMAB362 vs. 25.0% with EOX alone. Most of the responses were partial (28.6% vs. 21.4%, respectively) or stable disease (44.2% vs. 51.2%, respectively). There were only 10.4% complete responses with IMAB362 and 3.6% with EOX alone. About 12% of the patients in each arm were not evaluable, or the data were missing.
Both treatments were well tolerated, with most adverse effects being grade 1/2. However, there was more grade 3/4 neutropenia with the combination (32.5% vs. 21.4% for EOX alone) as well as grade 3/4 vomiting (10.4% vs. 3.6%, respectively). Grade 1/2 vomiting was common in both arms, with about one-third of patients receiving EOX alone and just over half of patients on EOX + IMAB362 being affected.
Dr. Al-Batran said that there may have been more vomiting with IMAB362 because tight junction proteins, including claudin, are present in the gastric mucosa. Diarrhea was largely grade 1/2, affected about one-third of patients receiving EOX alone, and was only about half as common among patients receiving the combination.
Dr. Al-Batran said this trial “provides a strong rationale for a confirmatory phase III trial.”
Press conference moderator Dr. Smitha Krishnamurthi said the study is important because it documents the activity of a first-in-class antibody in patients with advanced gastric and gastroesophageal junction cancers. Since CLDN18.2 is expressed in about 50% of these cancers, “this treatment could apply to many patients,” she said.
The study was initiated and sponsored by Ganymed Pharmaceuticals. Dr. Al-Batran has had a consulting or advisory role with Merck, Roche, Celgene, and Lilly; has been on the speakers bureau of Lilly, Roche, Celgene, and Nordic Bioscience; and has received research funding from Celgene, Roche Pharma, Lilly, Novartis, Vfor Pharma, Medac, and Hospira.
On Twitter @OncologyPractic
CHICAGO – The novel antibody IMAB362 extended survival of patients with advanced gastric cancer when added to chemotherapy, according to a phase II trial presented at the annual meeting of the Society of Clinical Oncology.
IMAB362 is a first-in-class monoclonal antibody targeting claudin18.2, a protein component of cellular tight junctions abundant in gastric tumors, as well as tumors of the pancreas, lung, esophagus, and ovaries.
IMAB362 significantly extended median overall survival (OS) when added to standard chemotherapy (13.2 vs. 8.4 months, hazard ratio [HR] = 0.51, P = .0001). Patients with the highest levels of claudin18.2 had an even longer median overall survival (16.7 vs. 9.0 months, HR = 0.45, P less than .0005).
The FAST (Phase II First-Line Therapy in Patients With Advanced CLDN18.2+ Gastric and Gastroesophageal Junction Adenocarcinoma) trial included patients who had no prior chemotherapy for locally advanced or metastatic disease. Tumors had to have 2+/3+ CLDN18.2 expression in 40% or more of tumor cells, and patients had an Eastern Cooperative Oncology Group performance status of 0-1.
Patients with tumors that expressed higher levels of claudin18,2, the target antigen, did better than the overall cohort in terms of progression-free survival (PFS), the primary endpoint.
“The FAST trial clearly met its primary endpoint, and there is a significant improvement in PFS and OS in the entire cohort and also in the higher expressers,” lead author Dr. Salah-Eddin Al-Batran, medical director of the Institute of Clinical Cancer Research, Nordwest Hospital in Frankfurst am Main, Germany, said in a news conference at the meeting.
The IMAB362 monoclonal antibody is highly specific for CLDN18.2 and works through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. In combination with chemotherapy, by binding to tumor debris, it is an immunomodulator of the tumor microenvironment.
About 50% of gastric tumors express CLDN18.2. After screening, the investigators randomized 246 patients to three treatment arms: epirubicin/oxaliplatin/capecitabine (EOX), n = 84; EOX + IMAB362 at a loading dose of 800 mg/m2, then 600 mg/m2 on day 1 every 3 weeks, n = 77; or a higher dose of IMAB362 with EOX, n = 85. Dr. Al-Batran reported results of the first two arms and will present results for the third arm at a later time.
Median progression-free survival was 4.8 months with EOX and 7.9 months with EOX plus IMAB362 (HR = .47; P = .0001).
If 70% or more of the tumor cells expressed CLDN18.2, IMAB362 improved the median PFS from 5.6 months for EOX alone to 7.2 months (HR = 0.36, P less than .0005), and OS improved from 9 months to 16.7 months (HR = 0.45, P less than .0005).
Response rates were also better with the addition of IMAB362. The objective response rate by RECIST criteria was 39.0% with EOX + IMAB362 vs. 25.0% with EOX alone. Most of the responses were partial (28.6% vs. 21.4%, respectively) or stable disease (44.2% vs. 51.2%, respectively). There were only 10.4% complete responses with IMAB362 and 3.6% with EOX alone. About 12% of the patients in each arm were not evaluable, or the data were missing.
Both treatments were well tolerated, with most adverse effects being grade 1/2. However, there was more grade 3/4 neutropenia with the combination (32.5% vs. 21.4% for EOX alone) as well as grade 3/4 vomiting (10.4% vs. 3.6%, respectively). Grade 1/2 vomiting was common in both arms, with about one-third of patients receiving EOX alone and just over half of patients on EOX + IMAB362 being affected.
Dr. Al-Batran said that there may have been more vomiting with IMAB362 because tight junction proteins, including claudin, are present in the gastric mucosa. Diarrhea was largely grade 1/2, affected about one-third of patients receiving EOX alone, and was only about half as common among patients receiving the combination.
Dr. Al-Batran said this trial “provides a strong rationale for a confirmatory phase III trial.”
Press conference moderator Dr. Smitha Krishnamurthi said the study is important because it documents the activity of a first-in-class antibody in patients with advanced gastric and gastroesophageal junction cancers. Since CLDN18.2 is expressed in about 50% of these cancers, “this treatment could apply to many patients,” she said.
The study was initiated and sponsored by Ganymed Pharmaceuticals. Dr. Al-Batran has had a consulting or advisory role with Merck, Roche, Celgene, and Lilly; has been on the speakers bureau of Lilly, Roche, Celgene, and Nordic Bioscience; and has received research funding from Celgene, Roche Pharma, Lilly, Novartis, Vfor Pharma, Medac, and Hospira.
On Twitter @OncologyPractic
AT THE 2016 ASCO ANNUAL MEETING
Key clinical point: A novel monoclonal antibody in combination with chemotherapy increased overall and progression-free survival in advanced gastric cancer, compared with chemotherapy alone.
Major finding: IMAB362 added to chemotherapy extended median overall survival from 8.4 months to 13.2 months over chemotherapy alone.
Data source: A phase II, randomized, active controlled study of 161 patients.
Disclosures: The study was initiated and sponsored by Ganymed Pharmaceuticals. Dr. Al-Batran has had a consulting or advisory role with Merck, Roche, Celgene, and Lilly; has been on the speakers bureau of Lilly, Roche, Celgene, and Nordic Bioscience; and has received research funding from Celgene, Roche Pharma, Lilly, Novartis, Vfor Pharma, Medac, and Hospira.
VIDEO: Direct-to-patient study empowers patients, accelerates research
CHICAGO – The Metastatic Breast Cancer Project is an innovative direct-to-patient initiative that allows metastatic breast cancer patients from around the country – often found through social media – to enroll themselves into a research study, primary investigator Dr. Nikhil Wagle said at the annual meeting of the American Society of Clinical Oncology.
Patients interested in participating can visit the project’s website and consent themselves into the study. Patients then fill out a questionnaire about their cancer and their treatments and provide a saliva sample using an at-home kit. Meanwhile, researchers obtain medical records and collect portions of stored tumor samples if available. The overarching goal of the project is to expedite metastatic breast cancer (MBC) genomics research by gaining access to a larger pool of patients with MBC and to generate novel research questions. Over 1,100 patients have already enrolled in the study, and many of them fall into groups of patients – such as those with extraordinary response to treatment or those of racial/ethnic minorities – that are normally challenging to capture in traditional studies.
In a video interview, Dr. Wagle of the Dana-Farber Cancer Institute in Boston and the Broad Institute in Cambridge, Mass., summarizes the unique benefits of the project and discusses future plans, which include gathering patient genomic data from blood biopsy samples and expanding the project to other types of cancers.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The Metastatic Breast Cancer Project is an innovative direct-to-patient initiative that allows metastatic breast cancer patients from around the country – often found through social media – to enroll themselves into a research study, primary investigator Dr. Nikhil Wagle said at the annual meeting of the American Society of Clinical Oncology.
Patients interested in participating can visit the project’s website and consent themselves into the study. Patients then fill out a questionnaire about their cancer and their treatments and provide a saliva sample using an at-home kit. Meanwhile, researchers obtain medical records and collect portions of stored tumor samples if available. The overarching goal of the project is to expedite metastatic breast cancer (MBC) genomics research by gaining access to a larger pool of patients with MBC and to generate novel research questions. Over 1,100 patients have already enrolled in the study, and many of them fall into groups of patients – such as those with extraordinary response to treatment or those of racial/ethnic minorities – that are normally challenging to capture in traditional studies.
In a video interview, Dr. Wagle of the Dana-Farber Cancer Institute in Boston and the Broad Institute in Cambridge, Mass., summarizes the unique benefits of the project and discusses future plans, which include gathering patient genomic data from blood biopsy samples and expanding the project to other types of cancers.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – The Metastatic Breast Cancer Project is an innovative direct-to-patient initiative that allows metastatic breast cancer patients from around the country – often found through social media – to enroll themselves into a research study, primary investigator Dr. Nikhil Wagle said at the annual meeting of the American Society of Clinical Oncology.
Patients interested in participating can visit the project’s website and consent themselves into the study. Patients then fill out a questionnaire about their cancer and their treatments and provide a saliva sample using an at-home kit. Meanwhile, researchers obtain medical records and collect portions of stored tumor samples if available. The overarching goal of the project is to expedite metastatic breast cancer (MBC) genomics research by gaining access to a larger pool of patients with MBC and to generate novel research questions. Over 1,100 patients have already enrolled in the study, and many of them fall into groups of patients – such as those with extraordinary response to treatment or those of racial/ethnic minorities – that are normally challenging to capture in traditional studies.
In a video interview, Dr. Wagle of the Dana-Farber Cancer Institute in Boston and the Broad Institute in Cambridge, Mass., summarizes the unique benefits of the project and discusses future plans, which include gathering patient genomic data from blood biopsy samples and expanding the project to other types of cancers.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE 2016 ASCO ANNUAL MEETING
‘Unprecedented’ efficacy for daratumumab in rel/ref MM
CHICAGO—The addition of the monoclonal antibody daratumumab to bortezomib and dexamethasone, the current standard of care for relapsed/refractory multiple myeloma (MM), has achieved progression-free survival that is “unprecedented in randomized studies that compared novel treatment” for this disease, according to Antonio Palumbo, MD, lead author of the phase 3 CASTOR study.
Dr Palumbo, of the University of Torino in Torino, Italy, presented the results on behalf of the CASTOR investigators during the plenary session of the 2016 ASCO Annual Meeting (abstract LBA4).
Daratumumab (Darzalex) is a human CD38 monoclonal antibody, which means it is targeted very specifically to the most relevant tumor antigen for plasma cells.
It also has direct major cytotoxic activity through the complement, which translates into major tumor reduction and a profound cytoreduction, Dr Palumbo said.
Even more important, he added, is that this is an immunomodulatory agent able to both increase the T-cell activity in the immune system, which controls the tumor, and also reduce the immunosuppressive regulatory cells that are suppressing the activity of the immune system.
Daratumumab is already approved by the US Food and Drug Administration and conditionally approved by the European Commission as a single agent for the treatment of relapsed/refractory multiple myeloma.
Study design
The CASTOR study was a multicenter, randomized, open-label, active-controlled phase 3 study.
Patients were eligible to enroll if they had relapsed or refractory MM with at least 1 prior line of therapy, which could include prior treatment with bortezomib, but they were not eligible if they were refractory to it.
Investigators randomized 251 patients to the experimental arm of daratumumab, bortezomib (Velcade), and dexamethasone (DVd) and 247 to the control arm of bortezomib and dexamethasone (Vd).
The dosing schedule was the same in both arms for bortezomib and dexamethasone. Patients in the experimental arm received daratumumab (16 mg/kg IV) every week for the first 3 cycles, on day 1 of cycles 4 – 8, and then every 4 weeks until progression.
The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included time to progression (TTP), overall survival (OS), overall response rate (ORR), very good partial response (VGPR), complete response (CR), minimal residual disease (MRD), time to response, and duration of response.
Patient demographics
Overall, patients had advanced stage disease with a long history of prior treatment.
They were a median age of 64 in both groups, and the time from diagnosis was a median 3.87 years in the experimental arm and 3.72 years in the control arm.
About 60% in both groups had had prior autologous stem cell transplant. Seventy-one percent in the experimental arm and 80% in the control arm had received a prior immunomodulatory drug, and 30% in the experimental arm and 34% in the control arm were refractory to their last line of therapy.
Dr Palumbo pointed out that accrual for the trial was rapid; 500 patients enrolled in 1 year, from September 2014 to September 2015.
“After 3 months, we already saw a difference in terms of efficacy,” he added, and the trial was stopped early. “So the median follow-up is short for this reason,” he explained, “and is around 7 months.”
The discontinuation rate was “as expected,” he said, “higher in the control arm,” with 44% discontinuing compared with 31% in the experimental arm.
Discontinuation for progressive disease was 25% in the control arm and 19% in the experimental arm, “showing already an advantage for the novel combination.”
Adverse events as reasons for discontinuation were 8% in the experimental arm and 10% in the control arm, “showing that the new agent is not adding any extra toxicity to the combination of bortezomib and dexamethasone.”
Efficacy
The “unprecedented” PFS, with a hazard ratio (HR) of 0.39 (95% CI, 0.28-0.53; P<0.0001), translated into a 61% reduction in the risk of disease progression or death for the experimental arm compared with the control arm.
The median PFS was not yet reached in the experimental arm, while the median PFS was 7.2 months in the control arm.
At 1 year, the PFS was 26.9% in the control arm and 60.7% in the experimental arm, “and this translates into a doubling in terms of remission duration for those patients,” Dr Palumbo stated.
“Even better was the outcome for the time to progression,” he said, with an HR of 0.30, “which means a 70% reduction in the risk of disease progression for DVd versus Vd, a more than doubling of time to disease progression.”
PFS by subgroup analysis showed that early intervention with daratumumab maximizes the efficacy of the combination.
For those patients who had received only 1 line of prior treatment, the HR was 0.31 (95% CI, 0.18 – 0.52; P<0.0001), which translated to a 69% reduction in the risk of progression or death for DVd compared with Vd.
The overall response rate revealed the profound cytoreduction achieved by the addition of daratumumab.
The CR rate increased from 9% in the control group to 19% in the experimental arm (P=0.0012), and the VGPR increased from 29% to 59%, in the control and experimental arms, respectively.
“So there is a doubling in the rate of CR and VGPR,” Dr Palumbo pointed out, “and this is quite relevant because more patients do achieve a profound cytoreduction.”
The rate of MRD negativity was 5 times higher for daratumumab-treated patients. Three percent of patients in the control arm were MRD negative (10-4) compared with 14% in the experimental arm.
Time to response, “in my opinion, is an important issue because . . . you can reach PR in around 1 month [with DVd] and this is clinically relevant because those patients are symptomatic,” he explained. “Reaching PR in 1 month means getting rid of pain in a quick way.”
“On the other hand, the achieving of CR requires a prolonged treatment,” he added. “CR is being achieved after 12 months of therapy, and MRD negativity might need even longer treatment.”
Safety
Daratumumab-treated patients experienced more thrombocytopenia and peripheral neuropathy (PN) of any grade than the control arm, 47% compared with 38%, respectively.
“But this is not due to the addition of the third agent,” Dr Palumbo clarified. “This is mainly the consequence, in the experimental arm, that treatment with bortezomib was longer in comparison to the control arm, and therefore, the typical toxicity of bortezomib—thrombocytopenia and PN—were slightly higher.”
There was also an increase in upper respiratory tract infections and cough in daratumumab-treated patients.
Grade 3-4 treatment-emergent adverse events occurring in more than 5% of patients included thrombocytopenia, anemia, neutropenia, lymphopenia, pneumonia, hypertension, and sensory PN.
However, grade 4 thrombocyotpenia, Dr Palumbo noted, did not translate into an increase in bleeding.
The major increase in toxicity due to daratumumab was in infusion-related reactions (IRRs), which occurred in 45% of patients. IRRs were consistent with the infusion of other monoclonal antibodies in cancer patients, he said, and 98% of patients with IRRs experienced them on the first infusion.
Conclusions
Dr Palumbo stressed that daratumumab did not increase the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.
Daratumumab significantly improved PFS and the response rate; the experimental combination was associated with a 61% reduction in the risk of progression or death.
The benefit was maintained across different subgroups—whether younger, older, good prognosis, bad prognosis, previously exposed to bortezomib or not exposed to bortezomib.
And DVd doubled both VGPR rates and CR rates.
In a press briefing, Dr Palumbo said that in the myeloma field, “we hope to have our R-CHOP, that has been a major treatment for lymphoma now also available with a different antibody for multiple myeloma.”
So the final conclusion, he added, is that “daratumumab-Vd might be considered today a new standard of care for relapsed and refractory multiple myeloma.”
The study was funded by Janssen Research & Development. 
CHICAGO—The addition of the monoclonal antibody daratumumab to bortezomib and dexamethasone, the current standard of care for relapsed/refractory multiple myeloma (MM), has achieved progression-free survival that is “unprecedented in randomized studies that compared novel treatment” for this disease, according to Antonio Palumbo, MD, lead author of the phase 3 CASTOR study.
Dr Palumbo, of the University of Torino in Torino, Italy, presented the results on behalf of the CASTOR investigators during the plenary session of the 2016 ASCO Annual Meeting (abstract LBA4).
Daratumumab (Darzalex) is a human CD38 monoclonal antibody, which means it is targeted very specifically to the most relevant tumor antigen for plasma cells.
It also has direct major cytotoxic activity through the complement, which translates into major tumor reduction and a profound cytoreduction, Dr Palumbo said.
Even more important, he added, is that this is an immunomodulatory agent able to both increase the T-cell activity in the immune system, which controls the tumor, and also reduce the immunosuppressive regulatory cells that are suppressing the activity of the immune system.
Daratumumab is already approved by the US Food and Drug Administration and conditionally approved by the European Commission as a single agent for the treatment of relapsed/refractory multiple myeloma.
Study design
The CASTOR study was a multicenter, randomized, open-label, active-controlled phase 3 study.
Patients were eligible to enroll if they had relapsed or refractory MM with at least 1 prior line of therapy, which could include prior treatment with bortezomib, but they were not eligible if they were refractory to it.
Investigators randomized 251 patients to the experimental arm of daratumumab, bortezomib (Velcade), and dexamethasone (DVd) and 247 to the control arm of bortezomib and dexamethasone (Vd).
The dosing schedule was the same in both arms for bortezomib and dexamethasone. Patients in the experimental arm received daratumumab (16 mg/kg IV) every week for the first 3 cycles, on day 1 of cycles 4 – 8, and then every 4 weeks until progression.
The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included time to progression (TTP), overall survival (OS), overall response rate (ORR), very good partial response (VGPR), complete response (CR), minimal residual disease (MRD), time to response, and duration of response.
Patient demographics
Overall, patients had advanced stage disease with a long history of prior treatment.
They were a median age of 64 in both groups, and the time from diagnosis was a median 3.87 years in the experimental arm and 3.72 years in the control arm.
About 60% in both groups had had prior autologous stem cell transplant. Seventy-one percent in the experimental arm and 80% in the control arm had received a prior immunomodulatory drug, and 30% in the experimental arm and 34% in the control arm were refractory to their last line of therapy.
Dr Palumbo pointed out that accrual for the trial was rapid; 500 patients enrolled in 1 year, from September 2014 to September 2015.
“After 3 months, we already saw a difference in terms of efficacy,” he added, and the trial was stopped early. “So the median follow-up is short for this reason,” he explained, “and is around 7 months.”
The discontinuation rate was “as expected,” he said, “higher in the control arm,” with 44% discontinuing compared with 31% in the experimental arm.
Discontinuation for progressive disease was 25% in the control arm and 19% in the experimental arm, “showing already an advantage for the novel combination.”
Adverse events as reasons for discontinuation were 8% in the experimental arm and 10% in the control arm, “showing that the new agent is not adding any extra toxicity to the combination of bortezomib and dexamethasone.”
Efficacy
The “unprecedented” PFS, with a hazard ratio (HR) of 0.39 (95% CI, 0.28-0.53; P<0.0001), translated into a 61% reduction in the risk of disease progression or death for the experimental arm compared with the control arm.
The median PFS was not yet reached in the experimental arm, while the median PFS was 7.2 months in the control arm.
At 1 year, the PFS was 26.9% in the control arm and 60.7% in the experimental arm, “and this translates into a doubling in terms of remission duration for those patients,” Dr Palumbo stated.
“Even better was the outcome for the time to progression,” he said, with an HR of 0.30, “which means a 70% reduction in the risk of disease progression for DVd versus Vd, a more than doubling of time to disease progression.”
PFS by subgroup analysis showed that early intervention with daratumumab maximizes the efficacy of the combination.
For those patients who had received only 1 line of prior treatment, the HR was 0.31 (95% CI, 0.18 – 0.52; P<0.0001), which translated to a 69% reduction in the risk of progression or death for DVd compared with Vd.
The overall response rate revealed the profound cytoreduction achieved by the addition of daratumumab.
The CR rate increased from 9% in the control group to 19% in the experimental arm (P=0.0012), and the VGPR increased from 29% to 59%, in the control and experimental arms, respectively.
“So there is a doubling in the rate of CR and VGPR,” Dr Palumbo pointed out, “and this is quite relevant because more patients do achieve a profound cytoreduction.”
The rate of MRD negativity was 5 times higher for daratumumab-treated patients. Three percent of patients in the control arm were MRD negative (10-4) compared with 14% in the experimental arm.
Time to response, “in my opinion, is an important issue because . . . you can reach PR in around 1 month [with DVd] and this is clinically relevant because those patients are symptomatic,” he explained. “Reaching PR in 1 month means getting rid of pain in a quick way.”
“On the other hand, the achieving of CR requires a prolonged treatment,” he added. “CR is being achieved after 12 months of therapy, and MRD negativity might need even longer treatment.”
Safety
Daratumumab-treated patients experienced more thrombocytopenia and peripheral neuropathy (PN) of any grade than the control arm, 47% compared with 38%, respectively.
“But this is not due to the addition of the third agent,” Dr Palumbo clarified. “This is mainly the consequence, in the experimental arm, that treatment with bortezomib was longer in comparison to the control arm, and therefore, the typical toxicity of bortezomib—thrombocytopenia and PN—were slightly higher.”
There was also an increase in upper respiratory tract infections and cough in daratumumab-treated patients.
Grade 3-4 treatment-emergent adverse events occurring in more than 5% of patients included thrombocytopenia, anemia, neutropenia, lymphopenia, pneumonia, hypertension, and sensory PN.
However, grade 4 thrombocyotpenia, Dr Palumbo noted, did not translate into an increase in bleeding.
The major increase in toxicity due to daratumumab was in infusion-related reactions (IRRs), which occurred in 45% of patients. IRRs were consistent with the infusion of other monoclonal antibodies in cancer patients, he said, and 98% of patients with IRRs experienced them on the first infusion.
Conclusions
Dr Palumbo stressed that daratumumab did not increase the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.
Daratumumab significantly improved PFS and the response rate; the experimental combination was associated with a 61% reduction in the risk of progression or death.
The benefit was maintained across different subgroups—whether younger, older, good prognosis, bad prognosis, previously exposed to bortezomib or not exposed to bortezomib.
And DVd doubled both VGPR rates and CR rates.
In a press briefing, Dr Palumbo said that in the myeloma field, “we hope to have our R-CHOP, that has been a major treatment for lymphoma now also available with a different antibody for multiple myeloma.”
So the final conclusion, he added, is that “daratumumab-Vd might be considered today a new standard of care for relapsed and refractory multiple myeloma.”
The study was funded by Janssen Research & Development.
CHICAGO—The addition of the monoclonal antibody daratumumab to bortezomib and dexamethasone, the current standard of care for relapsed/refractory multiple myeloma (MM), has achieved progression-free survival that is “unprecedented in randomized studies that compared novel treatment” for this disease, according to Antonio Palumbo, MD, lead author of the phase 3 CASTOR study.
Dr Palumbo, of the University of Torino in Torino, Italy, presented the results on behalf of the CASTOR investigators during the plenary session of the 2016 ASCO Annual Meeting (abstract LBA4).
Daratumumab (Darzalex) is a human CD38 monoclonal antibody, which means it is targeted very specifically to the most relevant tumor antigen for plasma cells.
It also has direct major cytotoxic activity through the complement, which translates into major tumor reduction and a profound cytoreduction, Dr Palumbo said.
Even more important, he added, is that this is an immunomodulatory agent able to both increase the T-cell activity in the immune system, which controls the tumor, and also reduce the immunosuppressive regulatory cells that are suppressing the activity of the immune system.
Daratumumab is already approved by the US Food and Drug Administration and conditionally approved by the European Commission as a single agent for the treatment of relapsed/refractory multiple myeloma.
Study design
The CASTOR study was a multicenter, randomized, open-label, active-controlled phase 3 study.
Patients were eligible to enroll if they had relapsed or refractory MM with at least 1 prior line of therapy, which could include prior treatment with bortezomib, but they were not eligible if they were refractory to it.
Investigators randomized 251 patients to the experimental arm of daratumumab, bortezomib (Velcade), and dexamethasone (DVd) and 247 to the control arm of bortezomib and dexamethasone (Vd).
The dosing schedule was the same in both arms for bortezomib and dexamethasone. Patients in the experimental arm received daratumumab (16 mg/kg IV) every week for the first 3 cycles, on day 1 of cycles 4 – 8, and then every 4 weeks until progression.
The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included time to progression (TTP), overall survival (OS), overall response rate (ORR), very good partial response (VGPR), complete response (CR), minimal residual disease (MRD), time to response, and duration of response.
Patient demographics
Overall, patients had advanced stage disease with a long history of prior treatment.
They were a median age of 64 in both groups, and the time from diagnosis was a median 3.87 years in the experimental arm and 3.72 years in the control arm.
About 60% in both groups had had prior autologous stem cell transplant. Seventy-one percent in the experimental arm and 80% in the control arm had received a prior immunomodulatory drug, and 30% in the experimental arm and 34% in the control arm were refractory to their last line of therapy.
Dr Palumbo pointed out that accrual for the trial was rapid; 500 patients enrolled in 1 year, from September 2014 to September 2015.
“After 3 months, we already saw a difference in terms of efficacy,” he added, and the trial was stopped early. “So the median follow-up is short for this reason,” he explained, “and is around 7 months.”
The discontinuation rate was “as expected,” he said, “higher in the control arm,” with 44% discontinuing compared with 31% in the experimental arm.
Discontinuation for progressive disease was 25% in the control arm and 19% in the experimental arm, “showing already an advantage for the novel combination.”
Adverse events as reasons for discontinuation were 8% in the experimental arm and 10% in the control arm, “showing that the new agent is not adding any extra toxicity to the combination of bortezomib and dexamethasone.”
Efficacy
The “unprecedented” PFS, with a hazard ratio (HR) of 0.39 (95% CI, 0.28-0.53; P<0.0001), translated into a 61% reduction in the risk of disease progression or death for the experimental arm compared with the control arm.
The median PFS was not yet reached in the experimental arm, while the median PFS was 7.2 months in the control arm.
At 1 year, the PFS was 26.9% in the control arm and 60.7% in the experimental arm, “and this translates into a doubling in terms of remission duration for those patients,” Dr Palumbo stated.
“Even better was the outcome for the time to progression,” he said, with an HR of 0.30, “which means a 70% reduction in the risk of disease progression for DVd versus Vd, a more than doubling of time to disease progression.”
PFS by subgroup analysis showed that early intervention with daratumumab maximizes the efficacy of the combination.
For those patients who had received only 1 line of prior treatment, the HR was 0.31 (95% CI, 0.18 – 0.52; P<0.0001), which translated to a 69% reduction in the risk of progression or death for DVd compared with Vd.
The overall response rate revealed the profound cytoreduction achieved by the addition of daratumumab.
The CR rate increased from 9% in the control group to 19% in the experimental arm (P=0.0012), and the VGPR increased from 29% to 59%, in the control and experimental arms, respectively.
“So there is a doubling in the rate of CR and VGPR,” Dr Palumbo pointed out, “and this is quite relevant because more patients do achieve a profound cytoreduction.”
The rate of MRD negativity was 5 times higher for daratumumab-treated patients. Three percent of patients in the control arm were MRD negative (10-4) compared with 14% in the experimental arm.
Time to response, “in my opinion, is an important issue because . . . you can reach PR in around 1 month [with DVd] and this is clinically relevant because those patients are symptomatic,” he explained. “Reaching PR in 1 month means getting rid of pain in a quick way.”
“On the other hand, the achieving of CR requires a prolonged treatment,” he added. “CR is being achieved after 12 months of therapy, and MRD negativity might need even longer treatment.”
Safety
Daratumumab-treated patients experienced more thrombocytopenia and peripheral neuropathy (PN) of any grade than the control arm, 47% compared with 38%, respectively.
“But this is not due to the addition of the third agent,” Dr Palumbo clarified. “This is mainly the consequence, in the experimental arm, that treatment with bortezomib was longer in comparison to the control arm, and therefore, the typical toxicity of bortezomib—thrombocytopenia and PN—were slightly higher.”
There was also an increase in upper respiratory tract infections and cough in daratumumab-treated patients.
Grade 3-4 treatment-emergent adverse events occurring in more than 5% of patients included thrombocytopenia, anemia, neutropenia, lymphopenia, pneumonia, hypertension, and sensory PN.
However, grade 4 thrombocyotpenia, Dr Palumbo noted, did not translate into an increase in bleeding.
The major increase in toxicity due to daratumumab was in infusion-related reactions (IRRs), which occurred in 45% of patients. IRRs were consistent with the infusion of other monoclonal antibodies in cancer patients, he said, and 98% of patients with IRRs experienced them on the first infusion.
Conclusions
Dr Palumbo stressed that daratumumab did not increase the cumulative toxicity or the toxicity of the bortezomib-dexamethasone combination.
Daratumumab significantly improved PFS and the response rate; the experimental combination was associated with a 61% reduction in the risk of progression or death.
The benefit was maintained across different subgroups—whether younger, older, good prognosis, bad prognosis, previously exposed to bortezomib or not exposed to bortezomib.
And DVd doubled both VGPR rates and CR rates.
In a press briefing, Dr Palumbo said that in the myeloma field, “we hope to have our R-CHOP, that has been a major treatment for lymphoma now also available with a different antibody for multiple myeloma.”
So the final conclusion, he added, is that “daratumumab-Vd might be considered today a new standard of care for relapsed and refractory multiple myeloma.”
The study was funded by Janssen Research & Development.
Hispanic, black AYA more likely to die of their cancer
© ASCO/Zach Boyden-Holmes
CHICAGO—Hispanic white and non-Hispanic black adolescents and young adults (AYA) are more likely to die of their disease than the same-aged white patients, according to a study presented at the 2016 ASCO Annual Meeting.
If the chance of a young-adult white patient dying within 2 years of receiving a liver cancer diagnosis is a baseline of 1, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient's chance of dying is 1.76.
And this holds true across cancer types, including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.
"What this means is that black and Hispanic young adult patients are almost 75% more likely to die after being diagnosed with liver cancer than are white young adult patients," said co-investigator Meryl Colton, a medical student at the University of Colorado.
Using data from the Surveillance, Epidemiologic and End Results (SEER) database, Colton and Adam L. Green, MD, of Children’s Hospital Colorado in Aurora, compared adolescents and young adults between the ages of 15 and 29 to evaluate racial/ethnic disparities in this age population, which is at particular risk for disparities in socioeconomic status and delayed diagnosis.
Even after controlling for insurance status and stage at diagnosis, the researchers determined that there were disparities in death rates for Hispanic whites, non-Hispanic blacks, and Hispanic blacks.
This implies that there is an influence of race/ethnicity independent of financial resources.
For leukemia, the hazard ratio was 1.15 for Hispanic whites and 1.05 for non-Hispanic blacks compared with non-Hispanic whites.
And for lymphoma, the hazard ratio was 1.28 for Hispanic whites and 1.07 for non-Hispanic blacks compared with the control group.
Colton points to 3 possible reasons for the disparity—residual socioeconomic factors that could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of the diseases to make cancers more dangerous in certain populations, or the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.
The researchers presented these findings as abstract 6557. They recommend further exploration to determine the mechanisms of these disparities.
© ASCO/Zach Boyden-Holmes
CHICAGO—Hispanic white and non-Hispanic black adolescents and young adults (AYA) are more likely to die of their disease than the same-aged white patients, according to a study presented at the 2016 ASCO Annual Meeting.
If the chance of a young-adult white patient dying within 2 years of receiving a liver cancer diagnosis is a baseline of 1, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient's chance of dying is 1.76.
And this holds true across cancer types, including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.
"What this means is that black and Hispanic young adult patients are almost 75% more likely to die after being diagnosed with liver cancer than are white young adult patients," said co-investigator Meryl Colton, a medical student at the University of Colorado.
Using data from the Surveillance, Epidemiologic and End Results (SEER) database, Colton and Adam L. Green, MD, of Children’s Hospital Colorado in Aurora, compared adolescents and young adults between the ages of 15 and 29 to evaluate racial/ethnic disparities in this age population, which is at particular risk for disparities in socioeconomic status and delayed diagnosis.
Even after controlling for insurance status and stage at diagnosis, the researchers determined that there were disparities in death rates for Hispanic whites, non-Hispanic blacks, and Hispanic blacks.
This implies that there is an influence of race/ethnicity independent of financial resources.
For leukemia, the hazard ratio was 1.15 for Hispanic whites and 1.05 for non-Hispanic blacks compared with non-Hispanic whites.
And for lymphoma, the hazard ratio was 1.28 for Hispanic whites and 1.07 for non-Hispanic blacks compared with the control group.
Colton points to 3 possible reasons for the disparity—residual socioeconomic factors that could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of the diseases to make cancers more dangerous in certain populations, or the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.
The researchers presented these findings as abstract 6557. They recommend further exploration to determine the mechanisms of these disparities.
© ASCO/Zach Boyden-Holmes
CHICAGO—Hispanic white and non-Hispanic black adolescents and young adults (AYA) are more likely to die of their disease than the same-aged white patients, according to a study presented at the 2016 ASCO Annual Meeting.
If the chance of a young-adult white patient dying within 2 years of receiving a liver cancer diagnosis is a baseline of 1, the chance of a similar Hispanic white patient dying is 1.77 and a non-Hispanic black patient's chance of dying is 1.76.
And this holds true across cancer types, including germ cell tumors, soft tissue sarcomas, lymphomas, and leukemias.
"What this means is that black and Hispanic young adult patients are almost 75% more likely to die after being diagnosed with liver cancer than are white young adult patients," said co-investigator Meryl Colton, a medical student at the University of Colorado.
Using data from the Surveillance, Epidemiologic and End Results (SEER) database, Colton and Adam L. Green, MD, of Children’s Hospital Colorado in Aurora, compared adolescents and young adults between the ages of 15 and 29 to evaluate racial/ethnic disparities in this age population, which is at particular risk for disparities in socioeconomic status and delayed diagnosis.
Even after controlling for insurance status and stage at diagnosis, the researchers determined that there were disparities in death rates for Hispanic whites, non-Hispanic blacks, and Hispanic blacks.
This implies that there is an influence of race/ethnicity independent of financial resources.
For leukemia, the hazard ratio was 1.15 for Hispanic whites and 1.05 for non-Hispanic blacks compared with non-Hispanic whites.
And for lymphoma, the hazard ratio was 1.28 for Hispanic whites and 1.07 for non-Hispanic blacks compared with the control group.
Colton points to 3 possible reasons for the disparity—residual socioeconomic factors that could influence a patient’s diagnosis and/or care, the possibility for genetically distinct forms of the diseases to make cancers more dangerous in certain populations, or the medical system fails to offer equal diagnosis and treatment across racial/ethnic groups.
The researchers presented these findings as abstract 6557. They recommend further exploration to determine the mechanisms of these disparities.
VIDEO: Immune checkpoint inhibitor is efficacious as first-line therapy for advanced bladder cancer
CHICAGO – Atezolizumab, an antibody that targets PD-L1, achieves a median survival of 14.8 months in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma, according to findings of the IMvigor210 trial’s cohort 1. Researchers presented the findings this week at the annual meeting of the American Society of Clinical Oncology.
In an interview at the meeting, lead author Dr. Arjun Vasant Balar of the department of medicine at the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, discussed the study and its implications. In particular, he weighed in on key issues, such as whether PD-L1 status predicts benefit and where atezolizumab may ultimately fit into the treatment armamentarium for this disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @OncologyPractic
CHICAGO – Atezolizumab, an antibody that targets PD-L1, achieves a median survival of 14.8 months in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma, according to findings of the IMvigor210 trial’s cohort 1. Researchers presented the findings this week at the annual meeting of the American Society of Clinical Oncology.
In an interview at the meeting, lead author Dr. Arjun Vasant Balar of the department of medicine at the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, discussed the study and its implications. In particular, he weighed in on key issues, such as whether PD-L1 status predicts benefit and where atezolizumab may ultimately fit into the treatment armamentarium for this disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @OncologyPractic
CHICAGO – Atezolizumab, an antibody that targets PD-L1, achieves a median survival of 14.8 months in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma, according to findings of the IMvigor210 trial’s cohort 1. Researchers presented the findings this week at the annual meeting of the American Society of Clinical Oncology.
In an interview at the meeting, lead author Dr. Arjun Vasant Balar of the department of medicine at the New York University Langone Medical Center and director of genitourinary medical oncology at the NYU Perlmutter Cancer Center, discussed the study and its implications. In particular, he weighed in on key issues, such as whether PD-L1 status predicts benefit and where atezolizumab may ultimately fit into the treatment armamentarium for this disease.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @OncologyPractic
AT THE 2016 ASCO ANNUAL MEETING
VIDEO: Dr. Maurie Markman says time to challenge established paradigms in cancer research
CHICAGO – When it comes to the tradition of waiting only for phase III randomized trial data to guide cancer treatment, it’s time to accept that things have changed, according to Dr. Maurie Markman.
“We don’t need a randomized trial to answer every question. That era is over, and we’ve got to get over it,” Dr. Markman of Cancer Treatment Centers of American in Boca Raton, Fla., said in a video interview at the annual meeting of the American Society of Clinical Oncology.
The new era is one of “big data,” and it requires a collective effort across the specialty to help guide treatment; ASCO’s CancerLinQ project is a good example, he said.
Dr. Markman tackled the topic of “Challenging Established Paradigms” as the invited discussant for four abstracts presented during a gynecologic cancer abstract session at the meeting, addressing phase II findings from the OV21/PETROC study of intraperitoneal (IP) versus intravenous chemotherapy after neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer, a phase II study of IP carboplatin plus intravenous dose-dense paclitaxel in patients with suboptimally debulked epithelial ovarian or primary peritoneal carcinoma, the phase III MITO8 study looking at prolonging the platinum-free interval in certain patients with ovarian cancer, and a phase II study of everolimus, letrozole, and metformin in women with advanced/recurrent endometrial cancer.
In a video interview he provides a brief summary of the “important and incredibly provocative” study findings, along with his take on their value for current practice, and he offers a vision for how new paradigms can change practice going forward.
Dr. Markman is a consultant or adviser for Amgen, BIND Biosciences, Boehringer Ingelheim, Celgene, Eisai, Genentech, and Hana BioSciences.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – When it comes to the tradition of waiting only for phase III randomized trial data to guide cancer treatment, it’s time to accept that things have changed, according to Dr. Maurie Markman.
“We don’t need a randomized trial to answer every question. That era is over, and we’ve got to get over it,” Dr. Markman of Cancer Treatment Centers of American in Boca Raton, Fla., said in a video interview at the annual meeting of the American Society of Clinical Oncology.
The new era is one of “big data,” and it requires a collective effort across the specialty to help guide treatment; ASCO’s CancerLinQ project is a good example, he said.
Dr. Markman tackled the topic of “Challenging Established Paradigms” as the invited discussant for four abstracts presented during a gynecologic cancer abstract session at the meeting, addressing phase II findings from the OV21/PETROC study of intraperitoneal (IP) versus intravenous chemotherapy after neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer, a phase II study of IP carboplatin plus intravenous dose-dense paclitaxel in patients with suboptimally debulked epithelial ovarian or primary peritoneal carcinoma, the phase III MITO8 study looking at prolonging the platinum-free interval in certain patients with ovarian cancer, and a phase II study of everolimus, letrozole, and metformin in women with advanced/recurrent endometrial cancer.
In a video interview he provides a brief summary of the “important and incredibly provocative” study findings, along with his take on their value for current practice, and he offers a vision for how new paradigms can change practice going forward.
Dr. Markman is a consultant or adviser for Amgen, BIND Biosciences, Boehringer Ingelheim, Celgene, Eisai, Genentech, and Hana BioSciences.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – When it comes to the tradition of waiting only for phase III randomized trial data to guide cancer treatment, it’s time to accept that things have changed, according to Dr. Maurie Markman.
“We don’t need a randomized trial to answer every question. That era is over, and we’ve got to get over it,” Dr. Markman of Cancer Treatment Centers of American in Boca Raton, Fla., said in a video interview at the annual meeting of the American Society of Clinical Oncology.
The new era is one of “big data,” and it requires a collective effort across the specialty to help guide treatment; ASCO’s CancerLinQ project is a good example, he said.
Dr. Markman tackled the topic of “Challenging Established Paradigms” as the invited discussant for four abstracts presented during a gynecologic cancer abstract session at the meeting, addressing phase II findings from the OV21/PETROC study of intraperitoneal (IP) versus intravenous chemotherapy after neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer, a phase II study of IP carboplatin plus intravenous dose-dense paclitaxel in patients with suboptimally debulked epithelial ovarian or primary peritoneal carcinoma, the phase III MITO8 study looking at prolonging the platinum-free interval in certain patients with ovarian cancer, and a phase II study of everolimus, letrozole, and metformin in women with advanced/recurrent endometrial cancer.
In a video interview he provides a brief summary of the “important and incredibly provocative” study findings, along with his take on their value for current practice, and he offers a vision for how new paradigms can change practice going forward.
Dr. Markman is a consultant or adviser for Amgen, BIND Biosciences, Boehringer Ingelheim, Celgene, Eisai, Genentech, and Hana BioSciences.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE 2016 ASCO ANNUAL MEETING
Brentuximab vedotin boosted PET-negative rate in Hodgkin
CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.
After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.
The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.
In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.
Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.
According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.
Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.
On Twitter @maryjodales
CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.
After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.
The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.
In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.
Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.
According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.
Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.
On Twitter @maryjodales
CHICAGO – Brentuximab vedotin appears to be safe and effective in eradicating residual disease after induction chemotherapy and may replace radiation for consolidation in patients with limited stage non-bulky Hodgkin lymphoma, Dr. Steven I. Park reported at the annual meeting of the American Society of Clinical Oncology.
After two cycles of ABVD [doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine], 72% of 40 evaluable patients achieved PET-negative disease. After completing brentuximab vedotin therapy, 90% of patients had PET-negative disease. With a median follow-up of 12 months, the estimated 1-year progression-free survival rate is 91%, and the overall survival rate is 96%.
The current standard therapy for limited stage Hodgkin lymphoma is about 4-6 cycles of chemotherapy with or without consolidative radiation therapy. The goal of the study was to reduce the number of cycles of chemotherapy and avoid radiation therapy, which has an unclear overall survival advantage and risks long-term side effects, noted Dr. Park of the University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center.
In this phase II multicenter study, 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma received ABVD followed by brentuximab vedotin (NCT01578967). Study patients’ median age was 29 years (range 19-67), and 46% presented with unfavorable disease. Over 90% of patients received four or fewer cycles of ABVD, and one patient received radiation due to disease progression.
Grade 3 or higher toxicities associated with brentuximab vedotin included neutropenia in three patients and peripheral neuropathy and rash in one patient each. One patient developed pancreatitis and died due to sepsis and hepatic failure, a rare complication of brentuximab vedotin that cautions regarding its use in patients with hepatic function limitations, Dr. Park said.
According to Seattle Genetics, the maker of brentuximab vedotin, the drug is an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to the cytotoxic agent monomethyl auristatin E, which leads to target cell death when internalized into CD30-expressing tumor cells.
Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.
On Twitter @maryjodales
AT THE 2016 ASCO ANNUAL MEETING
Key clinical point: Brentuximab vedotin appears to eradicate residual disease after induction chemotherapy in a small study of patients with limited stage non-bulky Hodgkin lymphoma.
Major finding: In 40 evaluable patients, 72% were PET-negative after two cycles of ABVD; brentuximab vedotin consolidation boosted PET-negative status to 90% of patients.
Data source: A phase II multicenter study of 41 patients with previously untreated limited stage non-bulky Hodgkin lymphoma.
Disclosures: Dr. Park disclosed research funding from Seattle Genetics, the maker of brentuximab vedotin, as well as Teva.
VIDEO: CPX-351 ‘new standard of care’ for older patients with secondary AML
CHICAGO – The investigational drug CPX-351 (Vyxeos) may become the new standard of care for older patients with secondary acute myeloid leukemia (AML), based on data presented at the annual meeting of the American Society of Clinical Oncology.
CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events as compared to the standard 7+3 regimen of cytarabine and daunorubicin.
In a video interview, primary investigator Dr. Jeffrey Lancet of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., discusses the data to be presented to the Food and Drug Administration for approval of the drug, and why the liposomal formulation of cytarabine and daunorubicin achieved superior results in these difficult to treat patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @maryjodales
CHICAGO – The investigational drug CPX-351 (Vyxeos) may become the new standard of care for older patients with secondary acute myeloid leukemia (AML), based on data presented at the annual meeting of the American Society of Clinical Oncology.
CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events as compared to the standard 7+3 regimen of cytarabine and daunorubicin.
In a video interview, primary investigator Dr. Jeffrey Lancet of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., discusses the data to be presented to the Food and Drug Administration for approval of the drug, and why the liposomal formulation of cytarabine and daunorubicin achieved superior results in these difficult to treat patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @maryjodales
CHICAGO – The investigational drug CPX-351 (Vyxeos) may become the new standard of care for older patients with secondary acute myeloid leukemia (AML), based on data presented at the annual meeting of the American Society of Clinical Oncology.
CPX-351 significantly improved overall survival, event-free survival, and treatment response without an increase in 60-day mortality or in the frequency and severity of adverse events as compared to the standard 7+3 regimen of cytarabine and daunorubicin.
In a video interview, primary investigator Dr. Jeffrey Lancet of H. Lee Moffitt Cancer Center & Research Institute, Tampa, Fla., discusses the data to be presented to the Food and Drug Administration for approval of the drug, and why the liposomal formulation of cytarabine and daunorubicin achieved superior results in these difficult to treat patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @maryjodales
AT THE 2016 ASCO ANNUAL MEETING
VIDEO: Dr. Roy Herbst talks combinations, evolutions, and innovations in lung cancer
CHICAGO – One of the main take-home messages in lung cancer this year is the efficacy and tolerability demonstrated in combining checkpoint inhibitors for small-cell lung cancer, Dr. Roy Herbst said in an interview at the annual meeting of the American Society of Clinical Oncology. Combining ipilimumab and nivolumab doubled the response rate in patients with progressive small-cell lung cancer, compared with those receiving only nivolumab.
“The evolution of immunotherapy studies continues to show that immunotherapies are here to stay,” Dr. Herbst said. The next step is to expand on how many respond to them. One possibility is to combine an antiangiogenesis agent with a checkpoint inhibitor to drive T cells into the tumor. Dr. Herbst discusses results he presented at the meeting showing safety and tolerability were achieved when combining pembrolizumab and ramucirumab in patients with non–small-cell lung cancer, and the response rate was close to 30%.
In the video interview, Dr. Herbst, professor and chief of medical oncology, Yale Comprehensive Cancer Center, New Haven, Conn., also discusses the evolution of EGFR and ALK inhibitors, a new antibody drug conjugate showing early promise in small cell lung cancer, and the future of liquid biopsies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @NikolaidesLaura
CHICAGO – One of the main take-home messages in lung cancer this year is the efficacy and tolerability demonstrated in combining checkpoint inhibitors for small-cell lung cancer, Dr. Roy Herbst said in an interview at the annual meeting of the American Society of Clinical Oncology. Combining ipilimumab and nivolumab doubled the response rate in patients with progressive small-cell lung cancer, compared with those receiving only nivolumab.
“The evolution of immunotherapy studies continues to show that immunotherapies are here to stay,” Dr. Herbst said. The next step is to expand on how many respond to them. One possibility is to combine an antiangiogenesis agent with a checkpoint inhibitor to drive T cells into the tumor. Dr. Herbst discusses results he presented at the meeting showing safety and tolerability were achieved when combining pembrolizumab and ramucirumab in patients with non–small-cell lung cancer, and the response rate was close to 30%.
In the video interview, Dr. Herbst, professor and chief of medical oncology, Yale Comprehensive Cancer Center, New Haven, Conn., also discusses the evolution of EGFR and ALK inhibitors, a new antibody drug conjugate showing early promise in small cell lung cancer, and the future of liquid biopsies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @NikolaidesLaura
CHICAGO – One of the main take-home messages in lung cancer this year is the efficacy and tolerability demonstrated in combining checkpoint inhibitors for small-cell lung cancer, Dr. Roy Herbst said in an interview at the annual meeting of the American Society of Clinical Oncology. Combining ipilimumab and nivolumab doubled the response rate in patients with progressive small-cell lung cancer, compared with those receiving only nivolumab.
“The evolution of immunotherapy studies continues to show that immunotherapies are here to stay,” Dr. Herbst said. The next step is to expand on how many respond to them. One possibility is to combine an antiangiogenesis agent with a checkpoint inhibitor to drive T cells into the tumor. Dr. Herbst discusses results he presented at the meeting showing safety and tolerability were achieved when combining pembrolizumab and ramucirumab in patients with non–small-cell lung cancer, and the response rate was close to 30%.
In the video interview, Dr. Herbst, professor and chief of medical oncology, Yale Comprehensive Cancer Center, New Haven, Conn., also discusses the evolution of EGFR and ALK inhibitors, a new antibody drug conjugate showing early promise in small cell lung cancer, and the future of liquid biopsies.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @NikolaidesLaura
EXPERT ANALYSIS FROM THE 2016 ASCO ANNUAL MEETING
VIDEO: Doctors should be challenged to extend AIs
CHICAGO – Extending adjuvant aromatase inhibitor treatment out to a decade reduced the risk of recurrence and the risk of a new breast cancer in postmenopausal women treated for early-stage breast cancer, Dr. Paul Goss reported at the annual meeting of the American Society of Clinical Oncology.
Women taking letrozole for five additional years had a 34% lower risk of disease-free survival events than those who received placebo, data from MA.17R showed. The annual incidence of contralateral breast cancer was .21% with extended letrozole vs. .49% with placebo. There was no difference in overall survival.
In an interview at the meeting, Dr. Goss discusses the “profoundly important result” and says doctors should be challenged if choosing not to extend treatment for their patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Extending adjuvant aromatase inhibitor treatment out to a decade reduced the risk of recurrence and the risk of a new breast cancer in postmenopausal women treated for early-stage breast cancer, Dr. Paul Goss reported at the annual meeting of the American Society of Clinical Oncology.
Women taking letrozole for five additional years had a 34% lower risk of disease-free survival events than those who received placebo, data from MA.17R showed. The annual incidence of contralateral breast cancer was .21% with extended letrozole vs. .49% with placebo. There was no difference in overall survival.
In an interview at the meeting, Dr. Goss discusses the “profoundly important result” and says doctors should be challenged if choosing not to extend treatment for their patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
CHICAGO – Extending adjuvant aromatase inhibitor treatment out to a decade reduced the risk of recurrence and the risk of a new breast cancer in postmenopausal women treated for early-stage breast cancer, Dr. Paul Goss reported at the annual meeting of the American Society of Clinical Oncology.
Women taking letrozole for five additional years had a 34% lower risk of disease-free survival events than those who received placebo, data from MA.17R showed. The annual incidence of contralateral breast cancer was .21% with extended letrozole vs. .49% with placebo. There was no difference in overall survival.
In an interview at the meeting, Dr. Goss discusses the “profoundly important result” and says doctors should be challenged if choosing not to extend treatment for their patients.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE 2016 ASCO ANNUAL MEETING
