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American Society of Clinical Oncology (ASCO): Annual Meeting
Inhibitor may fulfill unmet need in MF
© ASCO/Zach Boyden-Holmes
CHICAGO—The JAK2/FLT3 inhibitor pacritinib may fulfill an unmet need in the treatment of myelofibrosis (MF), according to a speaker at the 2015 ASCO Annual Meeting.
Results of the phase 3 PERSIST-1 trial indicate that pacritinib is safe and effective for MF patients with thrombocytopenia.
“Thrombocytopenia is a common feature in people with advanced [MF], and current treatment options have not been able to concurrently improve splenomegaly symptoms and cytopenias in these patients,” said study investigator Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center in Scottsdale, Arizona.
But PERSIST-1 showed that pacritinib can accomplish this. And the drug proved more effective than best available therapy (BAT), excluding JAK inhibitors, in reducing spleen volume and alleviating MF symptoms in the entire cohort of MF patients.
Dr Mesa presented these results at ASCO as abstract LBA7006. The study was funded by CTI BioPharma Corp., the company developing pacritinib.
The trial included 327 patients who were randomized to receive pacritinib (n=220) or BAT (n=107).
Patients in the BAT arm received therapies that are routinely prescribed off-label for MF, such as erythropoietin-stimulating agents, immunomodulatory drugs, and hydroxyurea. Ruxolitinib was intentionally excluded from this trial because the study included patients with thrombocytopenia.
Dr Mesa said the patients’ baseline characteristics “demonstrate a group of individuals with advanced myelofibrosis, a heavy percentage of those with primary myelofibrosis, the vast majority having intermediate-2 or high-risk disease, with very significant splenomegaly, and the vast majority having the JAK2 mutation.”
“About half the individuals were anemic or transfusion-dependent,” he noted. “And a full third were thrombocytopenic, under 100,000 [platelets/µL], with 16% under 50,000 [platelets/µL]. This was the first phase 3 study of myelofibrosis that allowed individuals with a platelet count of less than 100,000 to be enrolled.”
Fifty-six percent of patients remained on pacritinib at the time of analysis, as did 8% of patients on BAT. Seventy-nine percent of patients crossed over from the BAT arm to the pacritinib arm.
Spleen reduction
The study’s primary endpoint was a reduction in spleen volume of 35% or greater.
In the intent-to-treat (ITT) population, 19.1% of patients in the pacritinib arm met this endpoint, as did 4.7% of patients in the BAT arm (P=0.0003). In the evaluable population—165 patients in the pacritinib arm and 85 patients in the BAT arm—the rates were 25% and 5.9%, respectively (P=0.0001).
Dr Mesa noted that pacritinib was able to reduce spleen volume in all subgroups of patients, including those with thrombocytopenia.
“Both the group [with platelet counts] under 100,000 as well as under 50,000 uniquely responded only on the pacritinib arm, with no responses on the BAT arm,” he said.
In the ITT population, 16.7% of patients with platelet counts under 100,000/µL and 22.9% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values, in the comparison with the BAT arm, were 0.0451 and 0.0086, respectively.
In the evaluable population, 23.5% of patients with platelet counts under 100,000/µL and 33.3% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values were 0.0370 and 0.0072, respectively.
“It is too early to know if pacritinib has an impact on survival, but that is clearly our expectation [based on the spleen responses observed],” Dr Mesa said.
TSS and transfusion
The study’s secondary endpoint was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to week 24. TSS was measured by patient responses on the Myeloproliferative Neoplasm Symptom Assessment Form.
In the ITT population, 24.5% of pacritinib-treated patients and 6.5% of BAT-treated patients had a 50% or greater reduction in TSS score (P<0.0001). In the evaluable population, 40.9% and 9.9% of patients, respectively (P<0.0001), met this endpoint.
Dr Mesa also pointed out that 25.7% of pacritinib-treated patients who were severely anemic and transfusion-dependent—requiring at least 6 units of blood in the 90 days prior to study entry—became transfusion independent. But none of the BAT-treated patients did so (P<0.043).
Adverse events
“The most common adverse events [in the pacritinib arm] were consistent with the earlier studies,” Dr Mesa said. “Gastrointestinal toxicities were most common, although typically at low grades.”
“As expected, we saw very few individuals with any significant thrombocytopenia or anemia as drug-emergent. There were individuals who enrolled in the study as a grade 4, so some of those remained.”
The most common adverse events of any grade were diarrhea (53.2% in the pacritinib arm and 12.3% in the BAT arm), nausea (26.8% vs 6.6%), anemia (22.3% vs 19.8%), thrombocytopenia (16.8% vs 13.2%), and vomiting (15.9% vs 5.7%).
Ten percent of patients in the pacritinib arm required dose reductions due to adverse events. Diarrhea prompted dose interruptions in 13 patients and discontinuation in 3 patients. But pacritinib-associated diarrhea typically resolved in a little over a week.
“Based on these preliminary results, pacritinib may represent a very important agent for individuals with advanced disease and may have an impact on the disease course,” Dr Mesa concluded. 
© ASCO/Zach Boyden-Holmes
CHICAGO—The JAK2/FLT3 inhibitor pacritinib may fulfill an unmet need in the treatment of myelofibrosis (MF), according to a speaker at the 2015 ASCO Annual Meeting.
Results of the phase 3 PERSIST-1 trial indicate that pacritinib is safe and effective for MF patients with thrombocytopenia.
“Thrombocytopenia is a common feature in people with advanced [MF], and current treatment options have not been able to concurrently improve splenomegaly symptoms and cytopenias in these patients,” said study investigator Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center in Scottsdale, Arizona.
But PERSIST-1 showed that pacritinib can accomplish this. And the drug proved more effective than best available therapy (BAT), excluding JAK inhibitors, in reducing spleen volume and alleviating MF symptoms in the entire cohort of MF patients.
Dr Mesa presented these results at ASCO as abstract LBA7006. The study was funded by CTI BioPharma Corp., the company developing pacritinib.
The trial included 327 patients who were randomized to receive pacritinib (n=220) or BAT (n=107).
Patients in the BAT arm received therapies that are routinely prescribed off-label for MF, such as erythropoietin-stimulating agents, immunomodulatory drugs, and hydroxyurea. Ruxolitinib was intentionally excluded from this trial because the study included patients with thrombocytopenia.
Dr Mesa said the patients’ baseline characteristics “demonstrate a group of individuals with advanced myelofibrosis, a heavy percentage of those with primary myelofibrosis, the vast majority having intermediate-2 or high-risk disease, with very significant splenomegaly, and the vast majority having the JAK2 mutation.”
“About half the individuals were anemic or transfusion-dependent,” he noted. “And a full third were thrombocytopenic, under 100,000 [platelets/µL], with 16% under 50,000 [platelets/µL]. This was the first phase 3 study of myelofibrosis that allowed individuals with a platelet count of less than 100,000 to be enrolled.”
Fifty-six percent of patients remained on pacritinib at the time of analysis, as did 8% of patients on BAT. Seventy-nine percent of patients crossed over from the BAT arm to the pacritinib arm.
Spleen reduction
The study’s primary endpoint was a reduction in spleen volume of 35% or greater.
In the intent-to-treat (ITT) population, 19.1% of patients in the pacritinib arm met this endpoint, as did 4.7% of patients in the BAT arm (P=0.0003). In the evaluable population—165 patients in the pacritinib arm and 85 patients in the BAT arm—the rates were 25% and 5.9%, respectively (P=0.0001).
Dr Mesa noted that pacritinib was able to reduce spleen volume in all subgroups of patients, including those with thrombocytopenia.
“Both the group [with platelet counts] under 100,000 as well as under 50,000 uniquely responded only on the pacritinib arm, with no responses on the BAT arm,” he said.
In the ITT population, 16.7% of patients with platelet counts under 100,000/µL and 22.9% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values, in the comparison with the BAT arm, were 0.0451 and 0.0086, respectively.
In the evaluable population, 23.5% of patients with platelet counts under 100,000/µL and 33.3% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values were 0.0370 and 0.0072, respectively.
“It is too early to know if pacritinib has an impact on survival, but that is clearly our expectation [based on the spleen responses observed],” Dr Mesa said.
TSS and transfusion
The study’s secondary endpoint was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to week 24. TSS was measured by patient responses on the Myeloproliferative Neoplasm Symptom Assessment Form.
In the ITT population, 24.5% of pacritinib-treated patients and 6.5% of BAT-treated patients had a 50% or greater reduction in TSS score (P<0.0001). In the evaluable population, 40.9% and 9.9% of patients, respectively (P<0.0001), met this endpoint.
Dr Mesa also pointed out that 25.7% of pacritinib-treated patients who were severely anemic and transfusion-dependent—requiring at least 6 units of blood in the 90 days prior to study entry—became transfusion independent. But none of the BAT-treated patients did so (P<0.043).
Adverse events
“The most common adverse events [in the pacritinib arm] were consistent with the earlier studies,” Dr Mesa said. “Gastrointestinal toxicities were most common, although typically at low grades.”
“As expected, we saw very few individuals with any significant thrombocytopenia or anemia as drug-emergent. There were individuals who enrolled in the study as a grade 4, so some of those remained.”
The most common adverse events of any grade were diarrhea (53.2% in the pacritinib arm and 12.3% in the BAT arm), nausea (26.8% vs 6.6%), anemia (22.3% vs 19.8%), thrombocytopenia (16.8% vs 13.2%), and vomiting (15.9% vs 5.7%).
Ten percent of patients in the pacritinib arm required dose reductions due to adverse events. Diarrhea prompted dose interruptions in 13 patients and discontinuation in 3 patients. But pacritinib-associated diarrhea typically resolved in a little over a week.
“Based on these preliminary results, pacritinib may represent a very important agent for individuals with advanced disease and may have an impact on the disease course,” Dr Mesa concluded.
© ASCO/Zach Boyden-Holmes
CHICAGO—The JAK2/FLT3 inhibitor pacritinib may fulfill an unmet need in the treatment of myelofibrosis (MF), according to a speaker at the 2015 ASCO Annual Meeting.
Results of the phase 3 PERSIST-1 trial indicate that pacritinib is safe and effective for MF patients with thrombocytopenia.
“Thrombocytopenia is a common feature in people with advanced [MF], and current treatment options have not been able to concurrently improve splenomegaly symptoms and cytopenias in these patients,” said study investigator Ruben A. Mesa, MD, of the Mayo Clinic Cancer Center in Scottsdale, Arizona.
But PERSIST-1 showed that pacritinib can accomplish this. And the drug proved more effective than best available therapy (BAT), excluding JAK inhibitors, in reducing spleen volume and alleviating MF symptoms in the entire cohort of MF patients.
Dr Mesa presented these results at ASCO as abstract LBA7006. The study was funded by CTI BioPharma Corp., the company developing pacritinib.
The trial included 327 patients who were randomized to receive pacritinib (n=220) or BAT (n=107).
Patients in the BAT arm received therapies that are routinely prescribed off-label for MF, such as erythropoietin-stimulating agents, immunomodulatory drugs, and hydroxyurea. Ruxolitinib was intentionally excluded from this trial because the study included patients with thrombocytopenia.
Dr Mesa said the patients’ baseline characteristics “demonstrate a group of individuals with advanced myelofibrosis, a heavy percentage of those with primary myelofibrosis, the vast majority having intermediate-2 or high-risk disease, with very significant splenomegaly, and the vast majority having the JAK2 mutation.”
“About half the individuals were anemic or transfusion-dependent,” he noted. “And a full third were thrombocytopenic, under 100,000 [platelets/µL], with 16% under 50,000 [platelets/µL]. This was the first phase 3 study of myelofibrosis that allowed individuals with a platelet count of less than 100,000 to be enrolled.”
Fifty-six percent of patients remained on pacritinib at the time of analysis, as did 8% of patients on BAT. Seventy-nine percent of patients crossed over from the BAT arm to the pacritinib arm.
Spleen reduction
The study’s primary endpoint was a reduction in spleen volume of 35% or greater.
In the intent-to-treat (ITT) population, 19.1% of patients in the pacritinib arm met this endpoint, as did 4.7% of patients in the BAT arm (P=0.0003). In the evaluable population—165 patients in the pacritinib arm and 85 patients in the BAT arm—the rates were 25% and 5.9%, respectively (P=0.0001).
Dr Mesa noted that pacritinib was able to reduce spleen volume in all subgroups of patients, including those with thrombocytopenia.
“Both the group [with platelet counts] under 100,000 as well as under 50,000 uniquely responded only on the pacritinib arm, with no responses on the BAT arm,” he said.
In the ITT population, 16.7% of patients with platelet counts under 100,000/µL and 22.9% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values, in the comparison with the BAT arm, were 0.0451 and 0.0086, respectively.
In the evaluable population, 23.5% of patients with platelet counts under 100,000/µL and 33.3% of patients with platelet counts under 50,000/µL met the primary endpoint. The P values were 0.0370 and 0.0072, respectively.
“It is too early to know if pacritinib has an impact on survival, but that is clearly our expectation [based on the spleen responses observed],” Dr Mesa said.
TSS and transfusion
The study’s secondary endpoint was the proportion of patients with a 50% or greater reduction in Total Symptom Score (TSS) from baseline to week 24. TSS was measured by patient responses on the Myeloproliferative Neoplasm Symptom Assessment Form.
In the ITT population, 24.5% of pacritinib-treated patients and 6.5% of BAT-treated patients had a 50% or greater reduction in TSS score (P<0.0001). In the evaluable population, 40.9% and 9.9% of patients, respectively (P<0.0001), met this endpoint.
Dr Mesa also pointed out that 25.7% of pacritinib-treated patients who were severely anemic and transfusion-dependent—requiring at least 6 units of blood in the 90 days prior to study entry—became transfusion independent. But none of the BAT-treated patients did so (P<0.043).
Adverse events
“The most common adverse events [in the pacritinib arm] were consistent with the earlier studies,” Dr Mesa said. “Gastrointestinal toxicities were most common, although typically at low grades.”
“As expected, we saw very few individuals with any significant thrombocytopenia or anemia as drug-emergent. There were individuals who enrolled in the study as a grade 4, so some of those remained.”
The most common adverse events of any grade were diarrhea (53.2% in the pacritinib arm and 12.3% in the BAT arm), nausea (26.8% vs 6.6%), anemia (22.3% vs 19.8%), thrombocytopenia (16.8% vs 13.2%), and vomiting (15.9% vs 5.7%).
Ten percent of patients in the pacritinib arm required dose reductions due to adverse events. Diarrhea prompted dose interruptions in 13 patients and discontinuation in 3 patients. But pacritinib-associated diarrhea typically resolved in a little over a week.
“Based on these preliminary results, pacritinib may represent a very important agent for individuals with advanced disease and may have an impact on the disease course,” Dr Mesa concluded.
ASCO: Enzalutamide advances in triple-negative breast cancer
CHICAGO – The androgen-receptor inhibitor enzalutamide is active in patients with advanced triple-negative breast cancer that is immunohistochemically positive for this receptor, according to results of a phase II study reported at the annual meeting of the American Society of Clinical Oncology.
One-quarter of the 118 women in the single-arm, open-label trial had a response or achieved stable disease with the drug after 16 weeks, reported lead investigator Dr. Tiffany A. Traina of Memorial Sloan Kettering Cancer Center, New York.
However, more than one-third showed such benefit if their tumor was positive for a novel genomic diagnostic biomarker, PREDICT AR, which is based on genes showing differential expression between patients who do and do not respond to this therapy.
Furthermore, in multivariate analyses, androgen-receptor positivity by immunohistochemistry did not independently predict progression-free survival, but PREDICT AR positivity did.
“We find results of this phase II study to be compelling and warrant further investigation and development of enzalutamide for the treatment of patients with metastatic triple-negative breast cancer enriched by the biomarker,” Dr. Traina maintained.
Invited discussant Dr. Pamela N. Munster, a professor in the department of medicine (hematology/oncology) at the University of California, San Francisco, said, “I think the most exciting [finding] is the long overall survival using PREDICT AR as an assessment of androgen receptor and using enzalutamide as an androgen-receptor modulator.”
“I believe we really need an intense focus on biomarker refinement to move forward” in triple-negative breast cancer, she maintained. “We should use testing of targeted therapy for androgen receptor–positive early-stage breast cancer, possibly in the neoadjuvant setting. And immune therapy potentially in combination with hormone axis targeting for patients with triple-negative disease, at least those who have androgen receptor–positive and PD-L1–positive tumors, should be considered.”
A session attendee asked Dr. Traina whether she thought the androgen receptor is a predictive or prognostic marker. Data from a related poster presented at the meeting showed that PREDICT AR status in a separate, neoadjuvant cohort was not related to survival in the absence of enzalutamide, suggesting that this biomarker at least is not prognostic, she said.
Another attendee asked, “Do you have any plans to evaluate mutations in the androgen receptor, specifically the V7 mutation, which is found to mediate resistance to enzalutamide in prostate cancer?”
“I think there is a lot we could probably learn from our prostate cancer colleagues. I certainly have been,” Dr. Traina replied. “It’s an area that we are looking into, although I don’t think that we can presume to know the mutations or the mechanisms would be the same in breast as they are in prostate.”
Women were eligible to enroll in the Medivation-sponsored trial if their advanced triple-negative breast cancer showed any androgen-receptor positivity by immunohistochemistry, with no restriction on the number of prior therapies. They were treated with 160 mg daily of oral enzalutamide (Xtandi), which currently has Food and Drug Administration approval only for the treatment of prostate cancer.
With a median follow-up of 48 weeks, results showed that the 16-week rate of clinical benefit – a complete or partial response, or stable disease – was 25% in the intention-to-treat population (patients receiving at least one dose of the drug) and 35% in the evaluable population (the subset having androgen-receptor positivity of at least 10% of cells and at least one response assessment).
“This trial provides the first-ever RECIST-confirmed responses seen from an androgen-receptor antagonist,” Dr. Traina noted.
Median progression-free survival was 12.6 weeks in the intention-to-treat population overall, with somewhat greater benefit in patients having at least 10% of cells expressing androgen receptor. “While we could begin to see a group that might have better disease control, androgen receptor alone could not discriminate early on which patients were less likely to benefit,” she commented.
In a preplanned exploratory analysis looking at PREDICT AR (Parker et al.), nearly half of patients in the intent-to-treat population were positive for this marker. The 16-week clinical benefit rate was 39% in positive patients, more than triple the 11% seen in negative patients.
Most of the patients who were PREDICT AR positive but did not meet this endpoint were treated in the third-line setting or beyond, Dr. Traina noted. “PREDICT AR was developed in primary tumor tissue, and it may be that the biology drivers change over time and perhaps that may not apply to third-line therapy.”
Biomarker-positive patients also had better median progression-free survival in the intention-to-treat population (16.1 vs. 8.1 weeks). And in a multivariate analysis, PREDICT AR positivity was the only factor other than number of prior therapies to independently predict progression-free survival (hazard ratio, 0.45; P = .004) , according to Dr. Traina; notably, 10% or greater androgen-receptor positivity by immunohistochemistry did not.
An exploratory analysis additionally showed that patients with PREDICT AR–positive tumors had better median overall survival as well (not reached vs. 32.1 weeks), although data for this outcome are still not mature.
“This hormonal agent reflected a safety profile very much like what has been seen in prostate cancer,” she reported, with fatigue, nausea, and decreased appetite predominating. The overall rate of grade 3 or worse adverse events related to the drug was 10%. “There were no new safety signals found, and this was a well-tolerated regimen,” she added.
Dr. Traina disclosed that she receives honoraria from Celgene, Eisai, and Genentech; has a consulting or advisory role with AstraZeneca, Eisai, Genentech, Genentech/Roche, Halozyme, Medivation, Mundipharma, and Pfizer; and receives research funding from AstraZeneca, Eisai, Genentech, Janssen, Medivation, Novartis, and Ziopharm Oncology.
CHICAGO – The androgen-receptor inhibitor enzalutamide is active in patients with advanced triple-negative breast cancer that is immunohistochemically positive for this receptor, according to results of a phase II study reported at the annual meeting of the American Society of Clinical Oncology.
One-quarter of the 118 women in the single-arm, open-label trial had a response or achieved stable disease with the drug after 16 weeks, reported lead investigator Dr. Tiffany A. Traina of Memorial Sloan Kettering Cancer Center, New York.
However, more than one-third showed such benefit if their tumor was positive for a novel genomic diagnostic biomarker, PREDICT AR, which is based on genes showing differential expression between patients who do and do not respond to this therapy.
Furthermore, in multivariate analyses, androgen-receptor positivity by immunohistochemistry did not independently predict progression-free survival, but PREDICT AR positivity did.
“We find results of this phase II study to be compelling and warrant further investigation and development of enzalutamide for the treatment of patients with metastatic triple-negative breast cancer enriched by the biomarker,” Dr. Traina maintained.
Invited discussant Dr. Pamela N. Munster, a professor in the department of medicine (hematology/oncology) at the University of California, San Francisco, said, “I think the most exciting [finding] is the long overall survival using PREDICT AR as an assessment of androgen receptor and using enzalutamide as an androgen-receptor modulator.”
“I believe we really need an intense focus on biomarker refinement to move forward” in triple-negative breast cancer, she maintained. “We should use testing of targeted therapy for androgen receptor–positive early-stage breast cancer, possibly in the neoadjuvant setting. And immune therapy potentially in combination with hormone axis targeting for patients with triple-negative disease, at least those who have androgen receptor–positive and PD-L1–positive tumors, should be considered.”
A session attendee asked Dr. Traina whether she thought the androgen receptor is a predictive or prognostic marker. Data from a related poster presented at the meeting showed that PREDICT AR status in a separate, neoadjuvant cohort was not related to survival in the absence of enzalutamide, suggesting that this biomarker at least is not prognostic, she said.
Another attendee asked, “Do you have any plans to evaluate mutations in the androgen receptor, specifically the V7 mutation, which is found to mediate resistance to enzalutamide in prostate cancer?”
“I think there is a lot we could probably learn from our prostate cancer colleagues. I certainly have been,” Dr. Traina replied. “It’s an area that we are looking into, although I don’t think that we can presume to know the mutations or the mechanisms would be the same in breast as they are in prostate.”
Women were eligible to enroll in the Medivation-sponsored trial if their advanced triple-negative breast cancer showed any androgen-receptor positivity by immunohistochemistry, with no restriction on the number of prior therapies. They were treated with 160 mg daily of oral enzalutamide (Xtandi), which currently has Food and Drug Administration approval only for the treatment of prostate cancer.
With a median follow-up of 48 weeks, results showed that the 16-week rate of clinical benefit – a complete or partial response, or stable disease – was 25% in the intention-to-treat population (patients receiving at least one dose of the drug) and 35% in the evaluable population (the subset having androgen-receptor positivity of at least 10% of cells and at least one response assessment).
“This trial provides the first-ever RECIST-confirmed responses seen from an androgen-receptor antagonist,” Dr. Traina noted.
Median progression-free survival was 12.6 weeks in the intention-to-treat population overall, with somewhat greater benefit in patients having at least 10% of cells expressing androgen receptor. “While we could begin to see a group that might have better disease control, androgen receptor alone could not discriminate early on which patients were less likely to benefit,” she commented.
In a preplanned exploratory analysis looking at PREDICT AR (Parker et al.), nearly half of patients in the intent-to-treat population were positive for this marker. The 16-week clinical benefit rate was 39% in positive patients, more than triple the 11% seen in negative patients.
Most of the patients who were PREDICT AR positive but did not meet this endpoint were treated in the third-line setting or beyond, Dr. Traina noted. “PREDICT AR was developed in primary tumor tissue, and it may be that the biology drivers change over time and perhaps that may not apply to third-line therapy.”
Biomarker-positive patients also had better median progression-free survival in the intention-to-treat population (16.1 vs. 8.1 weeks). And in a multivariate analysis, PREDICT AR positivity was the only factor other than number of prior therapies to independently predict progression-free survival (hazard ratio, 0.45; P = .004) , according to Dr. Traina; notably, 10% or greater androgen-receptor positivity by immunohistochemistry did not.
An exploratory analysis additionally showed that patients with PREDICT AR–positive tumors had better median overall survival as well (not reached vs. 32.1 weeks), although data for this outcome are still not mature.
“This hormonal agent reflected a safety profile very much like what has been seen in prostate cancer,” she reported, with fatigue, nausea, and decreased appetite predominating. The overall rate of grade 3 or worse adverse events related to the drug was 10%. “There were no new safety signals found, and this was a well-tolerated regimen,” she added.
Dr. Traina disclosed that she receives honoraria from Celgene, Eisai, and Genentech; has a consulting or advisory role with AstraZeneca, Eisai, Genentech, Genentech/Roche, Halozyme, Medivation, Mundipharma, and Pfizer; and receives research funding from AstraZeneca, Eisai, Genentech, Janssen, Medivation, Novartis, and Ziopharm Oncology.
CHICAGO – The androgen-receptor inhibitor enzalutamide is active in patients with advanced triple-negative breast cancer that is immunohistochemically positive for this receptor, according to results of a phase II study reported at the annual meeting of the American Society of Clinical Oncology.
One-quarter of the 118 women in the single-arm, open-label trial had a response or achieved stable disease with the drug after 16 weeks, reported lead investigator Dr. Tiffany A. Traina of Memorial Sloan Kettering Cancer Center, New York.
However, more than one-third showed such benefit if their tumor was positive for a novel genomic diagnostic biomarker, PREDICT AR, which is based on genes showing differential expression between patients who do and do not respond to this therapy.
Furthermore, in multivariate analyses, androgen-receptor positivity by immunohistochemistry did not independently predict progression-free survival, but PREDICT AR positivity did.
“We find results of this phase II study to be compelling and warrant further investigation and development of enzalutamide for the treatment of patients with metastatic triple-negative breast cancer enriched by the biomarker,” Dr. Traina maintained.
Invited discussant Dr. Pamela N. Munster, a professor in the department of medicine (hematology/oncology) at the University of California, San Francisco, said, “I think the most exciting [finding] is the long overall survival using PREDICT AR as an assessment of androgen receptor and using enzalutamide as an androgen-receptor modulator.”
“I believe we really need an intense focus on biomarker refinement to move forward” in triple-negative breast cancer, she maintained. “We should use testing of targeted therapy for androgen receptor–positive early-stage breast cancer, possibly in the neoadjuvant setting. And immune therapy potentially in combination with hormone axis targeting for patients with triple-negative disease, at least those who have androgen receptor–positive and PD-L1–positive tumors, should be considered.”
A session attendee asked Dr. Traina whether she thought the androgen receptor is a predictive or prognostic marker. Data from a related poster presented at the meeting showed that PREDICT AR status in a separate, neoadjuvant cohort was not related to survival in the absence of enzalutamide, suggesting that this biomarker at least is not prognostic, she said.
Another attendee asked, “Do you have any plans to evaluate mutations in the androgen receptor, specifically the V7 mutation, which is found to mediate resistance to enzalutamide in prostate cancer?”
“I think there is a lot we could probably learn from our prostate cancer colleagues. I certainly have been,” Dr. Traina replied. “It’s an area that we are looking into, although I don’t think that we can presume to know the mutations or the mechanisms would be the same in breast as they are in prostate.”
Women were eligible to enroll in the Medivation-sponsored trial if their advanced triple-negative breast cancer showed any androgen-receptor positivity by immunohistochemistry, with no restriction on the number of prior therapies. They were treated with 160 mg daily of oral enzalutamide (Xtandi), which currently has Food and Drug Administration approval only for the treatment of prostate cancer.
With a median follow-up of 48 weeks, results showed that the 16-week rate of clinical benefit – a complete or partial response, or stable disease – was 25% in the intention-to-treat population (patients receiving at least one dose of the drug) and 35% in the evaluable population (the subset having androgen-receptor positivity of at least 10% of cells and at least one response assessment).
“This trial provides the first-ever RECIST-confirmed responses seen from an androgen-receptor antagonist,” Dr. Traina noted.
Median progression-free survival was 12.6 weeks in the intention-to-treat population overall, with somewhat greater benefit in patients having at least 10% of cells expressing androgen receptor. “While we could begin to see a group that might have better disease control, androgen receptor alone could not discriminate early on which patients were less likely to benefit,” she commented.
In a preplanned exploratory analysis looking at PREDICT AR (Parker et al.), nearly half of patients in the intent-to-treat population were positive for this marker. The 16-week clinical benefit rate was 39% in positive patients, more than triple the 11% seen in negative patients.
Most of the patients who were PREDICT AR positive but did not meet this endpoint were treated in the third-line setting or beyond, Dr. Traina noted. “PREDICT AR was developed in primary tumor tissue, and it may be that the biology drivers change over time and perhaps that may not apply to third-line therapy.”
Biomarker-positive patients also had better median progression-free survival in the intention-to-treat population (16.1 vs. 8.1 weeks). And in a multivariate analysis, PREDICT AR positivity was the only factor other than number of prior therapies to independently predict progression-free survival (hazard ratio, 0.45; P = .004) , according to Dr. Traina; notably, 10% or greater androgen-receptor positivity by immunohistochemistry did not.
An exploratory analysis additionally showed that patients with PREDICT AR–positive tumors had better median overall survival as well (not reached vs. 32.1 weeks), although data for this outcome are still not mature.
“This hormonal agent reflected a safety profile very much like what has been seen in prostate cancer,” she reported, with fatigue, nausea, and decreased appetite predominating. The overall rate of grade 3 or worse adverse events related to the drug was 10%. “There were no new safety signals found, and this was a well-tolerated regimen,” she added.
Dr. Traina disclosed that she receives honoraria from Celgene, Eisai, and Genentech; has a consulting or advisory role with AstraZeneca, Eisai, Genentech, Genentech/Roche, Halozyme, Medivation, Mundipharma, and Pfizer; and receives research funding from AstraZeneca, Eisai, Genentech, Janssen, Medivation, Novartis, and Ziopharm Oncology.
AT THE 2015 ASCO ANNUAL MEETING
Key clinical point: Enzalutamide is active in androgen receptor–positive triple-negative breast cancer.
Major finding: The 16-week clinical benefit rate was 25% in the intention-to-treat population.
Data source: A single-arm phase II trial in 118 patients with advanced triple-negative breast cancer positive for androgen receptors.
Disclosures: Dr. Traina disclosed that she receives honoraria from Celgene, Eisai, and Genentech; has a consulting or advisory role with AstraZeneca, Eisai, Genentech, Genentech/Roche, Halozyme, Medivation, Mundipharma, and Pfizer; and receives research funding from AstraZeneca, Eisai, Genentech, Janssen, Medivation, Novartis, and Ziopharm Oncology. The trial was sponsored by Medivation.
Upfront neck dissection boosts oral cancer survival
CHICAGO – Elective neck dissection at the time of primary surgery for early oral cancers increased overall survival by 12.5% compared with a watch-and-wait approach.
The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil K. D’Cruz from the head and neck service of the Tata Memorial Centre in Mumbai, India.
“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study. For every eight patients undergoing elective neck dissection, one death is prevented, and for every four patients who undergo elective neck dissection, one recurrence is prevented,” he said at a briefing prior to his presentation of the data in a plenary session at the annual meeting of the American Society of Clinical Oncology.
“Dr. D’Cruz should be congratulated on such a robust study that will impact the lives of potentially over 300,000 people with oral cancer globally. This is particularly important in countries and in populations where there are multiple barriers to health care. This ‘one and done’ approach we know now definitively improves survival,” commented ASCO Expert Dr. Jyoti D. Patel from the Feinberg School of Medicine at Northwestern University, Chicago.
Dr. Patel moderated the briefing, but was not involved in the study.
Results of the study are also published online in the New England Journal of Medicine.
Cancers of the lips and oral cavity are especially prevalent in countries where tobacco use and excessive alcohol consumption are common, with these two risk factors alone accounting for an estimated 90% of oral cancer diagnoses.
Until now, management of neck lymph nodes at the time of primary surgery for oral cancers has been controversial, due to a lack of clear evidence of a survival disadvantage to waiting until recurrence before performing a neck dissection, and to concerns about additional surgical procedures with their associated morbidities, including nerve injury and shoulder dysfunction, Dr. D’Cruz said in an interview.
In an attempt to settle the question, Dr. D’Cruz and colleagues conducted a randomized trial in which patients with early stage oral squamous cell carcinomas (stage T1-T2,N0) underwent perioral excision of the primary tumor and were then assigned to either elective neck dissection, or an observation (watch and wait) strategy to be followed by therapeutic neck dissection for nodal relapses.
The trial was terminated early because of evident benefit after 596 patients had been recruited. Dr. D’Cruz presented data from the second interim analysis of 500 patients with a least 9 months of follow-up, 245 of whom had been randomized to upfront neck dissection, and 255 of whom were assigned to watch-and-wait. There were 427 cancers of the tongue, 68 of the buccal mucosa, and 5 of the floor of the mouth.
At a median follow-up of 39 months, 50 patients treated with elective neck dissection had died, compared with 79 patients treated with observation, translating into a 12.5% improvement in overall survival for the elective strategy.
The upfront neck dissection strategy was associated with a 23.6% absolute increase in 3-year overall survival (80% vs. 67.5%, hazard ratio [HR] 0.63, P = .01). The benefits of elective dissection on both overall survival and disease-free survival remained after adjustment for stratification factors, Dr. D’Cruz said.
For the secondary endpoint of disease-free survival, there were 81 recurrences among patients treated with elective dissection, compared with 146 for those assigned to watch and wait. This translated into respective DFS rates of 69.5% and 45.9% (HR 0.45 P < .001).
The rates of adverse events were 6.6% for patients treated with elective dissection, compared with 3.6% for patients who underwent therapeutic dissection.
Dr. Hisham Mehanna, from the Institute of Head and Neck Studies and Eduation at the University of Birmingham, United Kingdom, the invited discussant, commented in the plenary that sentinel node biopsy might be an effective method for monitoring patients for recurrence, thus sparing the possible need for upfront dissection with its attendant morbidities. Surveillance by clinical follow-up alone, however, is not adequate, and in settings where only clinical follow-up is available (such as in low resource settings), elective neck dissection should become the standard of care, he recommended.
The study was sponsored by India’s Department of Atomic Energy Clinical Trial Center. Dr. D’Cruz and Dr. Patel reported having no disclosures relevant to the study.
CHICAGO – Elective neck dissection at the time of primary surgery for early oral cancers increased overall survival by 12.5% compared with a watch-and-wait approach.
The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil K. D’Cruz from the head and neck service of the Tata Memorial Centre in Mumbai, India.
“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study. For every eight patients undergoing elective neck dissection, one death is prevented, and for every four patients who undergo elective neck dissection, one recurrence is prevented,” he said at a briefing prior to his presentation of the data in a plenary session at the annual meeting of the American Society of Clinical Oncology.
“Dr. D’Cruz should be congratulated on such a robust study that will impact the lives of potentially over 300,000 people with oral cancer globally. This is particularly important in countries and in populations where there are multiple barriers to health care. This ‘one and done’ approach we know now definitively improves survival,” commented ASCO Expert Dr. Jyoti D. Patel from the Feinberg School of Medicine at Northwestern University, Chicago.
Dr. Patel moderated the briefing, but was not involved in the study.
Results of the study are also published online in the New England Journal of Medicine.
Cancers of the lips and oral cavity are especially prevalent in countries where tobacco use and excessive alcohol consumption are common, with these two risk factors alone accounting for an estimated 90% of oral cancer diagnoses.
Until now, management of neck lymph nodes at the time of primary surgery for oral cancers has been controversial, due to a lack of clear evidence of a survival disadvantage to waiting until recurrence before performing a neck dissection, and to concerns about additional surgical procedures with their associated morbidities, including nerve injury and shoulder dysfunction, Dr. D’Cruz said in an interview.
In an attempt to settle the question, Dr. D’Cruz and colleagues conducted a randomized trial in which patients with early stage oral squamous cell carcinomas (stage T1-T2,N0) underwent perioral excision of the primary tumor and were then assigned to either elective neck dissection, or an observation (watch and wait) strategy to be followed by therapeutic neck dissection for nodal relapses.
The trial was terminated early because of evident benefit after 596 patients had been recruited. Dr. D’Cruz presented data from the second interim analysis of 500 patients with a least 9 months of follow-up, 245 of whom had been randomized to upfront neck dissection, and 255 of whom were assigned to watch-and-wait. There were 427 cancers of the tongue, 68 of the buccal mucosa, and 5 of the floor of the mouth.
At a median follow-up of 39 months, 50 patients treated with elective neck dissection had died, compared with 79 patients treated with observation, translating into a 12.5% improvement in overall survival for the elective strategy.
The upfront neck dissection strategy was associated with a 23.6% absolute increase in 3-year overall survival (80% vs. 67.5%, hazard ratio [HR] 0.63, P = .01). The benefits of elective dissection on both overall survival and disease-free survival remained after adjustment for stratification factors, Dr. D’Cruz said.
For the secondary endpoint of disease-free survival, there were 81 recurrences among patients treated with elective dissection, compared with 146 for those assigned to watch and wait. This translated into respective DFS rates of 69.5% and 45.9% (HR 0.45 P < .001).
The rates of adverse events were 6.6% for patients treated with elective dissection, compared with 3.6% for patients who underwent therapeutic dissection.
Dr. Hisham Mehanna, from the Institute of Head and Neck Studies and Eduation at the University of Birmingham, United Kingdom, the invited discussant, commented in the plenary that sentinel node biopsy might be an effective method for monitoring patients for recurrence, thus sparing the possible need for upfront dissection with its attendant morbidities. Surveillance by clinical follow-up alone, however, is not adequate, and in settings where only clinical follow-up is available (such as in low resource settings), elective neck dissection should become the standard of care, he recommended.
The study was sponsored by India’s Department of Atomic Energy Clinical Trial Center. Dr. D’Cruz and Dr. Patel reported having no disclosures relevant to the study.
CHICAGO – Elective neck dissection at the time of primary surgery for early oral cancers increased overall survival by 12.5% compared with a watch-and-wait approach.
The risk of death was reduced by 36% among patients randomized in a phase III trial to neck lymph node dissection at the time of primary surgery, and the risk of recurrences was reduced by 55%, reported Dr. Anil K. D’Cruz from the head and neck service of the Tata Memorial Centre in Mumbai, India.
“Elective neck dissection should be the standard of care for early oral, node-negative squamous cell cancers, based on the findings of our study. For every eight patients undergoing elective neck dissection, one death is prevented, and for every four patients who undergo elective neck dissection, one recurrence is prevented,” he said at a briefing prior to his presentation of the data in a plenary session at the annual meeting of the American Society of Clinical Oncology.
“Dr. D’Cruz should be congratulated on such a robust study that will impact the lives of potentially over 300,000 people with oral cancer globally. This is particularly important in countries and in populations where there are multiple barriers to health care. This ‘one and done’ approach we know now definitively improves survival,” commented ASCO Expert Dr. Jyoti D. Patel from the Feinberg School of Medicine at Northwestern University, Chicago.
Dr. Patel moderated the briefing, but was not involved in the study.
Results of the study are also published online in the New England Journal of Medicine.
Cancers of the lips and oral cavity are especially prevalent in countries where tobacco use and excessive alcohol consumption are common, with these two risk factors alone accounting for an estimated 90% of oral cancer diagnoses.
Until now, management of neck lymph nodes at the time of primary surgery for oral cancers has been controversial, due to a lack of clear evidence of a survival disadvantage to waiting until recurrence before performing a neck dissection, and to concerns about additional surgical procedures with their associated morbidities, including nerve injury and shoulder dysfunction, Dr. D’Cruz said in an interview.
In an attempt to settle the question, Dr. D’Cruz and colleagues conducted a randomized trial in which patients with early stage oral squamous cell carcinomas (stage T1-T2,N0) underwent perioral excision of the primary tumor and were then assigned to either elective neck dissection, or an observation (watch and wait) strategy to be followed by therapeutic neck dissection for nodal relapses.
The trial was terminated early because of evident benefit after 596 patients had been recruited. Dr. D’Cruz presented data from the second interim analysis of 500 patients with a least 9 months of follow-up, 245 of whom had been randomized to upfront neck dissection, and 255 of whom were assigned to watch-and-wait. There were 427 cancers of the tongue, 68 of the buccal mucosa, and 5 of the floor of the mouth.
At a median follow-up of 39 months, 50 patients treated with elective neck dissection had died, compared with 79 patients treated with observation, translating into a 12.5% improvement in overall survival for the elective strategy.
The upfront neck dissection strategy was associated with a 23.6% absolute increase in 3-year overall survival (80% vs. 67.5%, hazard ratio [HR] 0.63, P = .01). The benefits of elective dissection on both overall survival and disease-free survival remained after adjustment for stratification factors, Dr. D’Cruz said.
For the secondary endpoint of disease-free survival, there were 81 recurrences among patients treated with elective dissection, compared with 146 for those assigned to watch and wait. This translated into respective DFS rates of 69.5% and 45.9% (HR 0.45 P < .001).
The rates of adverse events were 6.6% for patients treated with elective dissection, compared with 3.6% for patients who underwent therapeutic dissection.
Dr. Hisham Mehanna, from the Institute of Head and Neck Studies and Eduation at the University of Birmingham, United Kingdom, the invited discussant, commented in the plenary that sentinel node biopsy might be an effective method for monitoring patients for recurrence, thus sparing the possible need for upfront dissection with its attendant morbidities. Surveillance by clinical follow-up alone, however, is not adequate, and in settings where only clinical follow-up is available (such as in low resource settings), elective neck dissection should become the standard of care, he recommended.
The study was sponsored by India’s Department of Atomic Energy Clinical Trial Center. Dr. D’Cruz and Dr. Patel reported having no disclosures relevant to the study.
AT ASCO 2015
Key clinical point: Elective neck dissection at the time of primary surgery for oral cancers improves overall survival.
Major finding: Elective neck dissection improved overall survival by 12.5% compared with therapeutic dissection at the time of recurrence.
Data source: Randomized clinical trial halted early for efficacy; interim analysis of the first 500 patients with cancers of the tongue, buccosal mucosa, and floor of the mouth.
Disclosures: The study was sponsored by India’s Department of Atomic Energy Clinical Trial Center. Dr. D’Cruz and Dr. Patel reported having no disclosures relavent to the study.
VIDEO: Palbociclib may delay chemotherapy for some women with metastatic breast cancer
CHICAGO – PALOMA-3 lead study author, Dr. Nicholas C. Turner, discusses the phase III trial findings, which indicate the possibility of delaying chemotherapy in some women with metastatic breast cancer.
Dr. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, says in an interview that the findings suggest the use of palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy.
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 – PALOMA-3 lead study author, Dr. Nicholas C. Turner, discusses the phase III trial findings, which indicate the possibility of delaying chemotherapy in some women with metastatic breast cancer.
Dr. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, says in an interview that the findings suggest the use of palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy.
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 – PALOMA-3 lead study author, Dr. Nicholas C. Turner, discusses the phase III trial findings, which indicate the possibility of delaying chemotherapy in some women with metastatic breast cancer.
Dr. Turner, a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London, says in an interview that the findings suggest the use of palbociclib—a first-in-class oral inhibitor of CDKs 4 and 6 that prevents cell cycle progression—may delay the need for chemotherapy in women with hormone receptor–positive, HER2-negative metastatic breast cancer that is showing resistance to endocrine therapy.
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 ASCO 2015
ASCO: Eribulin results ‘a giant step for sarcoma’
CHICAGO – For the first time ever, a new drug has shown a survival advantage – albeit a small one – in metastatic soft tissue sarcomas, diseases that are almost without exception unresponsive to medical therapies and rapidly fatal.
In a randomized, phase III trial, median overall survival for patients with metastatic leiomyosarcoma or liposarcoma treated with eribulin (Halaven) was 13.5 months compared with 11.5 months for patients treated with dacarbazine.
“For me as a clinical oncologist, this a clinically meaningful result given the unmet need in this rare, hard-to-treat family of diseases,” said lead investigator Dr. Patrick Schöffski, professor of medicine and head of experimental oncology lab at University Hospitals in Leuven, Belgium, at the annual meeting of the American Society of Clinical Oncology.
“I’ve been an oncologist for over 20 years, and there has never been a positive sarcoma study for survival – ever,” said ASCO expert Dr. Gary K. Schwartz, chief of hematology and oncology at Columbia University, New York, who was not involved in the study. “This is the first positive sarcoma study showing a survival benefit with any chemotherapy in the history of medical oncology.”
The findings represent “a small step for cancer, and a giant step for sarcoma.” Dr. Schwartz said at a press briefing.
In an interview, he added that he was “shocked” when he found out that the survival benefit with eribulin was seen in patients with liposarcoma as well as leiomyosarcoma. “I thought that the benefit would only be in patients with leiomyosarcoma,” he said.
Leiomyosarcoma and liposarcoma, also called adipocytic sarcoma, are two of the most common histologic subtypes of highly uncommon soft tissue sarcomas. Patients with advanced metastatic sarcomas generally have a very poor prognosis and precious few treatment options.
Eribulin is a synthetic analogue of halichondrin B, a macrolide antibiotic isolated from a sea sponge that has strong cytotoxic properties. In preclinical studies, it was shown to kill cancer cells via anti-mitotic effects. It is approved in the United States for treatment of patients with metastatic breast cancer for whom at least two other lines of therapy have failed.
Dr. Schöffski and colleagues in centers in the United States, Europe, and Korea randomly assigned patients with metastatic intermediate or high-grade leiomyosarcoma or liposarcoma to receive either eribulin 1.4 mg/m2 on days 1 and 8 of 21-day cycles (228 patients), or conventional therapy with dacarbazine 850, 1,000, or 1,200 mg/m2 on day 1 of every 21 day cycle (224 patients).
The majority of patients had undergone at least two prior regimens for advanced disease.
The trial met its primary endpoint of an overall survival advantage, with median OS of 13.5 months for patients on eribulin, compared with 11.5 months for those on dacarbazine. The hazard ratio (HR) was 0.768 favoring eirbulin (P = .0169).
The median progression-free survival was 2.6 months in each group.
In all, 26% of patients on eribulin and 14% on dacarbazine required dose reductions, and 8% and 5%, respectively, discontinued therapy because of treatment-emergent adverse events.
The most common grade 3 or greater toxicities in each arm were neutropenia, fatigue, and nausea. The adverse events in general were in line with known safety profiles for each agent, Dr. Schöffski said.
There were 10 deaths among patients on eribulin, two of which were attributed to the drug (1 neutropenic sepsis and one sepsis). There were three deaths among patients on dacarbazine, none attributed to therapy.
In an interview, Dr. Schöffski noted that he has treated one patient, a man with dedifferentiated liposarcoma, with 46 cycles of eribulin, “so we see activity in a tumor type that is notoriously resistant to established drugs.”
He said that moving forward, investigators may wish to test eribulin in combination with other drugs, such as therapies targeted to genetic mutations, immunotherapies, or other approaches.
The study was sponsored by Eisai, Inc. Dr. Schöffski and Dr. Schwartz reported having no relevant conflicts of interest.
CHICAGO – For the first time ever, a new drug has shown a survival advantage – albeit a small one – in metastatic soft tissue sarcomas, diseases that are almost without exception unresponsive to medical therapies and rapidly fatal.
In a randomized, phase III trial, median overall survival for patients with metastatic leiomyosarcoma or liposarcoma treated with eribulin (Halaven) was 13.5 months compared with 11.5 months for patients treated with dacarbazine.
“For me as a clinical oncologist, this a clinically meaningful result given the unmet need in this rare, hard-to-treat family of diseases,” said lead investigator Dr. Patrick Schöffski, professor of medicine and head of experimental oncology lab at University Hospitals in Leuven, Belgium, at the annual meeting of the American Society of Clinical Oncology.
“I’ve been an oncologist for over 20 years, and there has never been a positive sarcoma study for survival – ever,” said ASCO expert Dr. Gary K. Schwartz, chief of hematology and oncology at Columbia University, New York, who was not involved in the study. “This is the first positive sarcoma study showing a survival benefit with any chemotherapy in the history of medical oncology.”
The findings represent “a small step for cancer, and a giant step for sarcoma.” Dr. Schwartz said at a press briefing.
In an interview, he added that he was “shocked” when he found out that the survival benefit with eribulin was seen in patients with liposarcoma as well as leiomyosarcoma. “I thought that the benefit would only be in patients with leiomyosarcoma,” he said.
Leiomyosarcoma and liposarcoma, also called adipocytic sarcoma, are two of the most common histologic subtypes of highly uncommon soft tissue sarcomas. Patients with advanced metastatic sarcomas generally have a very poor prognosis and precious few treatment options.
Eribulin is a synthetic analogue of halichondrin B, a macrolide antibiotic isolated from a sea sponge that has strong cytotoxic properties. In preclinical studies, it was shown to kill cancer cells via anti-mitotic effects. It is approved in the United States for treatment of patients with metastatic breast cancer for whom at least two other lines of therapy have failed.
Dr. Schöffski and colleagues in centers in the United States, Europe, and Korea randomly assigned patients with metastatic intermediate or high-grade leiomyosarcoma or liposarcoma to receive either eribulin 1.4 mg/m2 on days 1 and 8 of 21-day cycles (228 patients), or conventional therapy with dacarbazine 850, 1,000, or 1,200 mg/m2 on day 1 of every 21 day cycle (224 patients).
The majority of patients had undergone at least two prior regimens for advanced disease.
The trial met its primary endpoint of an overall survival advantage, with median OS of 13.5 months for patients on eribulin, compared with 11.5 months for those on dacarbazine. The hazard ratio (HR) was 0.768 favoring eirbulin (P = .0169).
The median progression-free survival was 2.6 months in each group.
In all, 26% of patients on eribulin and 14% on dacarbazine required dose reductions, and 8% and 5%, respectively, discontinued therapy because of treatment-emergent adverse events.
The most common grade 3 or greater toxicities in each arm were neutropenia, fatigue, and nausea. The adverse events in general were in line with known safety profiles for each agent, Dr. Schöffski said.
There were 10 deaths among patients on eribulin, two of which were attributed to the drug (1 neutropenic sepsis and one sepsis). There were three deaths among patients on dacarbazine, none attributed to therapy.
In an interview, Dr. Schöffski noted that he has treated one patient, a man with dedifferentiated liposarcoma, with 46 cycles of eribulin, “so we see activity in a tumor type that is notoriously resistant to established drugs.”
He said that moving forward, investigators may wish to test eribulin in combination with other drugs, such as therapies targeted to genetic mutations, immunotherapies, or other approaches.
The study was sponsored by Eisai, Inc. Dr. Schöffski and Dr. Schwartz reported having no relevant conflicts of interest.
CHICAGO – For the first time ever, a new drug has shown a survival advantage – albeit a small one – in metastatic soft tissue sarcomas, diseases that are almost without exception unresponsive to medical therapies and rapidly fatal.
In a randomized, phase III trial, median overall survival for patients with metastatic leiomyosarcoma or liposarcoma treated with eribulin (Halaven) was 13.5 months compared with 11.5 months for patients treated with dacarbazine.
“For me as a clinical oncologist, this a clinically meaningful result given the unmet need in this rare, hard-to-treat family of diseases,” said lead investigator Dr. Patrick Schöffski, professor of medicine and head of experimental oncology lab at University Hospitals in Leuven, Belgium, at the annual meeting of the American Society of Clinical Oncology.
“I’ve been an oncologist for over 20 years, and there has never been a positive sarcoma study for survival – ever,” said ASCO expert Dr. Gary K. Schwartz, chief of hematology and oncology at Columbia University, New York, who was not involved in the study. “This is the first positive sarcoma study showing a survival benefit with any chemotherapy in the history of medical oncology.”
The findings represent “a small step for cancer, and a giant step for sarcoma.” Dr. Schwartz said at a press briefing.
In an interview, he added that he was “shocked” when he found out that the survival benefit with eribulin was seen in patients with liposarcoma as well as leiomyosarcoma. “I thought that the benefit would only be in patients with leiomyosarcoma,” he said.
Leiomyosarcoma and liposarcoma, also called adipocytic sarcoma, are two of the most common histologic subtypes of highly uncommon soft tissue sarcomas. Patients with advanced metastatic sarcomas generally have a very poor prognosis and precious few treatment options.
Eribulin is a synthetic analogue of halichondrin B, a macrolide antibiotic isolated from a sea sponge that has strong cytotoxic properties. In preclinical studies, it was shown to kill cancer cells via anti-mitotic effects. It is approved in the United States for treatment of patients with metastatic breast cancer for whom at least two other lines of therapy have failed.
Dr. Schöffski and colleagues in centers in the United States, Europe, and Korea randomly assigned patients with metastatic intermediate or high-grade leiomyosarcoma or liposarcoma to receive either eribulin 1.4 mg/m2 on days 1 and 8 of 21-day cycles (228 patients), or conventional therapy with dacarbazine 850, 1,000, or 1,200 mg/m2 on day 1 of every 21 day cycle (224 patients).
The majority of patients had undergone at least two prior regimens for advanced disease.
The trial met its primary endpoint of an overall survival advantage, with median OS of 13.5 months for patients on eribulin, compared with 11.5 months for those on dacarbazine. The hazard ratio (HR) was 0.768 favoring eirbulin (P = .0169).
The median progression-free survival was 2.6 months in each group.
In all, 26% of patients on eribulin and 14% on dacarbazine required dose reductions, and 8% and 5%, respectively, discontinued therapy because of treatment-emergent adverse events.
The most common grade 3 or greater toxicities in each arm were neutropenia, fatigue, and nausea. The adverse events in general were in line with known safety profiles for each agent, Dr. Schöffski said.
There were 10 deaths among patients on eribulin, two of which were attributed to the drug (1 neutropenic sepsis and one sepsis). There were three deaths among patients on dacarbazine, none attributed to therapy.
In an interview, Dr. Schöffski noted that he has treated one patient, a man with dedifferentiated liposarcoma, with 46 cycles of eribulin, “so we see activity in a tumor type that is notoriously resistant to established drugs.”
He said that moving forward, investigators may wish to test eribulin in combination with other drugs, such as therapies targeted to genetic mutations, immunotherapies, or other approaches.
The study was sponsored by Eisai, Inc. Dr. Schöffski and Dr. Schwartz reported having no relevant conflicts of interest.
AT ASCO 2015
Key clinical point: Eribulin is the first drug shown in a clinical trial to offer a survival advantage over existing therapies for metastatic soft-tissue sarcomas.
Major finding: Median overall survival was 13.5 months for patients treated with eribulin vs. 11.5 months for those treated with dacarbazine.
Data source: Randomized clinical trial in 452 patients with metastatic leiomyosarcoma or liposarcoma.
Disclosures: The study was sponsored by Eisai, Inc. Dr. Schöffski reported having no relevant conflicts of interest.
ASCO: German trial argues against complete nodal dissection for SLN-positive melanoma
CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).
With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.
“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”
However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.
“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.
The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”
Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.
With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.
The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.
Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.
CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).
With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.
“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”
However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.
“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.
The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”
Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.
With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.
The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.
Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.
CHICAGO – The case against performing a complete lymph node dissection in patients with melanoma who have micrometastases in their sentinel lymph node just got stronger in light of findings from a randomized, phase III clinical trial conducted by the German Dermatologic Cooperative Oncology Group (DeCOG).
With 483 patients studied and a median follow-up approaching 3 years, the rate of distant metastasis–free survival did not differ significantly between those who had a complete lymph node dissection and those who had simple watchful waiting, with just 0.3% separating the groups, the investigators reported at the annual meeting of the American Society of Clinical Oncology. Most other key outcomes were likewise statistically indistinguishable between groups.
“This is the first study which tested the general recommendation of complete lymphadenectomy in patients with positive nodes,” senior investigator Dr. Claus Garbe, a professor of dermatology at the University of Tübingen (Germany), said in a press briefing. “We cannot confirm this recommendation, and we expect that the surgical [practice] will change.”
However, Dr. Lynn Schuchter, an ASCO expert, as well as chief of hematology oncology and the C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine in Philadelphia, took a more cautious view, saying that the findings require confirmation before being widely adopted into clinical practice.
“I would say this is a really important study. However, it’s a relatively small study, and I don’t think we would make a complete change in our recommendations yet based upon this study,” she commented.
The ongoing international Multicenter Selective Lymphadenectomy Trial II (MSLT-II), which has a target enrollment of about 1,900 patients and is designed to detect a smaller difference between groups, will provide further information on this issue, according to Dr. Schuchter. “So I think we’ll wait in terms of making definitive changes in our management, for the results of another, larger study with longer follow-up,” she said. “But [the German study] gives us, in that patient who is very concerned about lymphedema ... pertinent information to feel comfortable considering more of a watch-and-wait approach, in terms of monitoring somebody and not doing that surgery.”
Dr. Garbe and colleagues enrolled in their trial patients who underwent resection of a primary cutaneous melanoma of the trunk or extremities at least 1.00 mm in thickness and were determined to have stage III disease with a positive sentinel node containing individual tumor cells or micrometastases. They were randomly assigned to observation only or complete lymph node dissection. Both groups had a lymph node ultrasound exam every 3 months and CT/MRI or PET scans every 6 months.
With a median follow-up of 35 months, patients who had the complete lymph node dissection were about half as likely to develop regional metastases as peers who had watchful waiting (8.3% vs. 14.6%). But the groups did not differ significantly with respect to 3- and 5-year rates of recurrence-free survival, distant metastasis–free survival (the trial’s primary endpoint), and melanoma-specific survival.
The investigators plan to repeat their analysis in 3 years but do not expect the findings will change, according to Dr. Garbe, as the large majority of melanoma recurrences happen in the first 3 years after initial diagnosis.
Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.
AT ASCO 2015
Key clinical point: Complete nodal dissection fails to reduce distant metastasis in patients with melanoma who have micrometastases in sentinel nodes.
Major finding: Patients who did and did not undergo complete lymph node dissection were statistically indistinguishable with respect to distant metastases–free survival, recurrence-free survival, and melanoma-specific survival.
Data source: A randomized, phase III trial in 483 patients with stage III melanoma and micrometastases in their sentinel nodes.
Disclosures: Dr. Garbe disclosed ties to Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, and Roche Pharma AG. The trial was funded by German Cancer Aid.
Novel antibody evokes responses in relapsed/refractory myeloma
CHICAGO – An investigational targeted therapy for multiple myeloma delayed disease progression in patients for whom as many as five prior lines of therapy had failed.
Daratumumab, an experimental antibody targeted to the CD38 receptor expressed at high levels on the surface of myeloma cells, was associated with a 29.2% overall response rate (ORR) at a median follow-up of 9.4 months, including three patients with a complete remission, said Dr. Saad Zafar Usmani of Levine Cancer Institute–Carolinas Healthcare System, Charlotte, N.C.
“Daratumumab monotherapy produced unprecedented overall responses that deepened over time in this heavily pretreated multiple myeloma patient population. These results highlight the potential of daratumumab as a novel, well-tolerated, single-agent therapy in various stages of myeloma treatment,” Dr. Usmani said at a briefing prior to the presentation of the data in a session at the annual meeting of the American Society of Clinical Oncology.
The results support further exploration of daratumumab in combination with currently available therapies for multiple myeloma, he added.
In the dose-selection portion of a phase II open-label, international, multicenter study, patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or who had no treatment response to the most recent proteasome inhibitor and immunomodulator, were randomly assigned to receive either 8 mg/kg or 16 mg/kg daratumumab. After a response evaluation, the 16 mg/kg dose was chosen, and an additional 90 patients were enrolled at this dose.
As noted, the overall response rate, the primary endpoint, was 29.2%, consisting of three stringent complete responses, 10 very good partial responses, and 18 partial responses. The median duration of response was 7.4 months. The responses were consistent across all clinically relevant subgroups, Dr. Usmani said.
The median time to progression was 3.7 months. Median overall survival had not been reached at the time of the last data analysis, and the estimated 1-year overall survival rate was 65%.
At a median follow-up of 9.4 months, 14 of 31 patients with responses remained on therapy.
Patients tolerated the 16 mg/kg dose well, and none discontinued because of drug-related events.
Minor infusion site reactions (grade 1 or 2) were common during the first infusion and were managed with standard therapies, Dr. Usmani said.
“This is the first monoclonal antibody in myeloma that has shown single-agent activity,” Dr. Usmani said.
ASCO expert Dr. Merry-Jennifer Markham from the University of Florida in Gainesville, who was not involved in the study, commented that “there have been substantial treatment advances in multiple myeloma over the last decade, and daratumumab will be an important addition to the list of options. This therapy may offer a glimmer of hope for those myeloma patients who have run out of treatment options.
The study was funded by Janssen Research and Development. Dr. Usmani is on the speaker’s bureau for Janssen Oncology.
CHICAGO – An investigational targeted therapy for multiple myeloma delayed disease progression in patients for whom as many as five prior lines of therapy had failed.
Daratumumab, an experimental antibody targeted to the CD38 receptor expressed at high levels on the surface of myeloma cells, was associated with a 29.2% overall response rate (ORR) at a median follow-up of 9.4 months, including three patients with a complete remission, said Dr. Saad Zafar Usmani of Levine Cancer Institute–Carolinas Healthcare System, Charlotte, N.C.
“Daratumumab monotherapy produced unprecedented overall responses that deepened over time in this heavily pretreated multiple myeloma patient population. These results highlight the potential of daratumumab as a novel, well-tolerated, single-agent therapy in various stages of myeloma treatment,” Dr. Usmani said at a briefing prior to the presentation of the data in a session at the annual meeting of the American Society of Clinical Oncology.
The results support further exploration of daratumumab in combination with currently available therapies for multiple myeloma, he added.
In the dose-selection portion of a phase II open-label, international, multicenter study, patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or who had no treatment response to the most recent proteasome inhibitor and immunomodulator, were randomly assigned to receive either 8 mg/kg or 16 mg/kg daratumumab. After a response evaluation, the 16 mg/kg dose was chosen, and an additional 90 patients were enrolled at this dose.
As noted, the overall response rate, the primary endpoint, was 29.2%, consisting of three stringent complete responses, 10 very good partial responses, and 18 partial responses. The median duration of response was 7.4 months. The responses were consistent across all clinically relevant subgroups, Dr. Usmani said.
The median time to progression was 3.7 months. Median overall survival had not been reached at the time of the last data analysis, and the estimated 1-year overall survival rate was 65%.
At a median follow-up of 9.4 months, 14 of 31 patients with responses remained on therapy.
Patients tolerated the 16 mg/kg dose well, and none discontinued because of drug-related events.
Minor infusion site reactions (grade 1 or 2) were common during the first infusion and were managed with standard therapies, Dr. Usmani said.
“This is the first monoclonal antibody in myeloma that has shown single-agent activity,” Dr. Usmani said.
ASCO expert Dr. Merry-Jennifer Markham from the University of Florida in Gainesville, who was not involved in the study, commented that “there have been substantial treatment advances in multiple myeloma over the last decade, and daratumumab will be an important addition to the list of options. This therapy may offer a glimmer of hope for those myeloma patients who have run out of treatment options.
The study was funded by Janssen Research and Development. Dr. Usmani is on the speaker’s bureau for Janssen Oncology.
CHICAGO – An investigational targeted therapy for multiple myeloma delayed disease progression in patients for whom as many as five prior lines of therapy had failed.
Daratumumab, an experimental antibody targeted to the CD38 receptor expressed at high levels on the surface of myeloma cells, was associated with a 29.2% overall response rate (ORR) at a median follow-up of 9.4 months, including three patients with a complete remission, said Dr. Saad Zafar Usmani of Levine Cancer Institute–Carolinas Healthcare System, Charlotte, N.C.
“Daratumumab monotherapy produced unprecedented overall responses that deepened over time in this heavily pretreated multiple myeloma patient population. These results highlight the potential of daratumumab as a novel, well-tolerated, single-agent therapy in various stages of myeloma treatment,” Dr. Usmani said at a briefing prior to the presentation of the data in a session at the annual meeting of the American Society of Clinical Oncology.
The results support further exploration of daratumumab in combination with currently available therapies for multiple myeloma, he added.
In the dose-selection portion of a phase II open-label, international, multicenter study, patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent, or who had no treatment response to the most recent proteasome inhibitor and immunomodulator, were randomly assigned to receive either 8 mg/kg or 16 mg/kg daratumumab. After a response evaluation, the 16 mg/kg dose was chosen, and an additional 90 patients were enrolled at this dose.
As noted, the overall response rate, the primary endpoint, was 29.2%, consisting of three stringent complete responses, 10 very good partial responses, and 18 partial responses. The median duration of response was 7.4 months. The responses were consistent across all clinically relevant subgroups, Dr. Usmani said.
The median time to progression was 3.7 months. Median overall survival had not been reached at the time of the last data analysis, and the estimated 1-year overall survival rate was 65%.
At a median follow-up of 9.4 months, 14 of 31 patients with responses remained on therapy.
Patients tolerated the 16 mg/kg dose well, and none discontinued because of drug-related events.
Minor infusion site reactions (grade 1 or 2) were common during the first infusion and were managed with standard therapies, Dr. Usmani said.
“This is the first monoclonal antibody in myeloma that has shown single-agent activity,” Dr. Usmani said.
ASCO expert Dr. Merry-Jennifer Markham from the University of Florida in Gainesville, who was not involved in the study, commented that “there have been substantial treatment advances in multiple myeloma over the last decade, and daratumumab will be an important addition to the list of options. This therapy may offer a glimmer of hope for those myeloma patients who have run out of treatment options.
The study was funded by Janssen Research and Development. Dr. Usmani is on the speaker’s bureau for Janssen Oncology.
AT ASCO 2015
Key clinical point: The investigational monoclonal antibody daratumumab was effective in patients with heavily pretreated multiple myeloma.
Major finding: The overall response rate to daratumumab monotherapy was 29.2%.
Data source: A phase II open-label trial in 108 patients with previously treated or refractory multiple myeloma.
Disclosures: The study was funded by Janssen Research and Development. Dr. Usmani is on the speaker’s bureau for Janssen Oncology.
Adding ibrutinib to chemoimmunotherapy improves outcomes of relapsed CLL
CHICAGO – Adding the targeted agent ibrutinib to standard chemoimmunotherapy prolongs progression-free survival in patients with relapsed chronic lymphocytic leukemia (CLL), according to interim results of a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.
Findings of the international trial, known as HELIOS, showed that the risk of progression or death was 80% lower for patients given ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), than for counterparts given a placebo, each in addition to standard bendamustine and rituximab. As a result, the trial was unblinded and all patients were offered ibrutinib.
“Today the world for CLL relapsed patients will be different because of this particular drug,” lead study author Dr. Asher Chanan-Khan, professor of medicine at Mayo Clinic in Jacksonville, Florida, commented in a press briefing. “This becomes one of the most important changing points in the history of CLL, where the treatment of CLL patients will no longer be bendamustine and rituximab, but bendamustine and rituximab with ibrutinib.”
“This is very exciting for our CLL patients, who have a chronic cancer; all of them will relapse and recur,” noted Dr. Merry-Jennifer Markham, an ASCO Expert from the Division of Hematology & Oncology, University of Florida in Gainesville. “We have lots of options for treatment, but the results of this combination are so exciting for them. I think this is really going to be an important drug in combination with an established chemotherapy regimen. It will really help these patients live longer, and longer lives with better quality.”
Signaling through the BTK pathway plays a critical role in the survival and proliferation of CLL cells, making treatment with ibrutinib especially attractive, according to Dr. Chanan-Khan. Results of the sister RESONATE trial established that the drug performed well when given as monotherapy to patients with relapsed or refractory CLL (N. Engl. J. Med. 2014 ;371:213-2).
Last year, the U.S. Food and Drug Administration granted accelerated approval to ibrutinib for treating CLL in patients who have already received other treatments.
In the new, Janssen-funded trial, 578 patients with CLL or small lymphocytic lymphoma, excluding those with the 17p deletion, were randomized evenly to receive ibrutinib (brand name Imbruvica) or placebo, each in addition to bendamustine (Treanda) and rituximab (Rituxan). On the basis of the sister trial’s data, the protocol was amended after the trial began to allow placebo patients to cross over to ibrutinib at the time of progression, noted Dr. Chanan-Khan.
The preplanned interim analysis, conducted after a median follow-up of 17 months, showed that median progression-free survival – the trial’s primary endpoint – was 13.3 months in the placebo group, whereas this landmark had not been reached in the ibrutinib group (hazard ratio, 0.20; P < .0001). Benefit was similar in the subgroup of patients with high-risk features.
Ibrutinib was also associated with a near-significant improvement in overall survival relative to placebo (HR, 0.63; P = .0598), a noteworthy finding as roughly a third of patients in the placebo arm had crossed over to the drug at progression, Dr. Chanan-Khan pointed out. The ibrutinib group had a superior overall response rate as well (82.7% vs. 67.8%; P < .0001).
“The side effect profile was very tolerable and expected for each of the individual drugs that were in this regimen,” he reported. The most common side effects – neutropenia, thrombocytopenia, diarrhea, and nausea – occurred in similar proportions in each group.
With respect to side effects known to be specific to ibrutinib, bleeding of any grade occurred in 31% of patients given the drug, compared with 17% given placebo, and serious bleeding occurred in 3.8%. Atrial fibrillation occurred in 7% with the drug, compared with 0.7% with placebo, but the proportion developing grade 3 or 4 atrial fibrillation was only about 2%.
As for future research, the investigators plan to evaluate ibrutinib alone and in combination with drugs targeting the CD20 protein in patients with newly diagnosed symptomatic and asymptomatic CLL.
Dr. Chanan-Khan reported having no financial disclosures. The trial was funded by Janssen.
CHICAGO – Adding the targeted agent ibrutinib to standard chemoimmunotherapy prolongs progression-free survival in patients with relapsed chronic lymphocytic leukemia (CLL), according to interim results of a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.
Findings of the international trial, known as HELIOS, showed that the risk of progression or death was 80% lower for patients given ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), than for counterparts given a placebo, each in addition to standard bendamustine and rituximab. As a result, the trial was unblinded and all patients were offered ibrutinib.
“Today the world for CLL relapsed patients will be different because of this particular drug,” lead study author Dr. Asher Chanan-Khan, professor of medicine at Mayo Clinic in Jacksonville, Florida, commented in a press briefing. “This becomes one of the most important changing points in the history of CLL, where the treatment of CLL patients will no longer be bendamustine and rituximab, but bendamustine and rituximab with ibrutinib.”
“This is very exciting for our CLL patients, who have a chronic cancer; all of them will relapse and recur,” noted Dr. Merry-Jennifer Markham, an ASCO Expert from the Division of Hematology & Oncology, University of Florida in Gainesville. “We have lots of options for treatment, but the results of this combination are so exciting for them. I think this is really going to be an important drug in combination with an established chemotherapy regimen. It will really help these patients live longer, and longer lives with better quality.”
Signaling through the BTK pathway plays a critical role in the survival and proliferation of CLL cells, making treatment with ibrutinib especially attractive, according to Dr. Chanan-Khan. Results of the sister RESONATE trial established that the drug performed well when given as monotherapy to patients with relapsed or refractory CLL (N. Engl. J. Med. 2014 ;371:213-2).
Last year, the U.S. Food and Drug Administration granted accelerated approval to ibrutinib for treating CLL in patients who have already received other treatments.
In the new, Janssen-funded trial, 578 patients with CLL or small lymphocytic lymphoma, excluding those with the 17p deletion, were randomized evenly to receive ibrutinib (brand name Imbruvica) or placebo, each in addition to bendamustine (Treanda) and rituximab (Rituxan). On the basis of the sister trial’s data, the protocol was amended after the trial began to allow placebo patients to cross over to ibrutinib at the time of progression, noted Dr. Chanan-Khan.
The preplanned interim analysis, conducted after a median follow-up of 17 months, showed that median progression-free survival – the trial’s primary endpoint – was 13.3 months in the placebo group, whereas this landmark had not been reached in the ibrutinib group (hazard ratio, 0.20; P < .0001). Benefit was similar in the subgroup of patients with high-risk features.
Ibrutinib was also associated with a near-significant improvement in overall survival relative to placebo (HR, 0.63; P = .0598), a noteworthy finding as roughly a third of patients in the placebo arm had crossed over to the drug at progression, Dr. Chanan-Khan pointed out. The ibrutinib group had a superior overall response rate as well (82.7% vs. 67.8%; P < .0001).
“The side effect profile was very tolerable and expected for each of the individual drugs that were in this regimen,” he reported. The most common side effects – neutropenia, thrombocytopenia, diarrhea, and nausea – occurred in similar proportions in each group.
With respect to side effects known to be specific to ibrutinib, bleeding of any grade occurred in 31% of patients given the drug, compared with 17% given placebo, and serious bleeding occurred in 3.8%. Atrial fibrillation occurred in 7% with the drug, compared with 0.7% with placebo, but the proportion developing grade 3 or 4 atrial fibrillation was only about 2%.
As for future research, the investigators plan to evaluate ibrutinib alone and in combination with drugs targeting the CD20 protein in patients with newly diagnosed symptomatic and asymptomatic CLL.
Dr. Chanan-Khan reported having no financial disclosures. The trial was funded by Janssen.
CHICAGO – Adding the targeted agent ibrutinib to standard chemoimmunotherapy prolongs progression-free survival in patients with relapsed chronic lymphocytic leukemia (CLL), according to interim results of a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.
Findings of the international trial, known as HELIOS, showed that the risk of progression or death was 80% lower for patients given ibrutinib, an oral inhibitor of Bruton’s tyrosine kinase (BTK), than for counterparts given a placebo, each in addition to standard bendamustine and rituximab. As a result, the trial was unblinded and all patients were offered ibrutinib.
“Today the world for CLL relapsed patients will be different because of this particular drug,” lead study author Dr. Asher Chanan-Khan, professor of medicine at Mayo Clinic in Jacksonville, Florida, commented in a press briefing. “This becomes one of the most important changing points in the history of CLL, where the treatment of CLL patients will no longer be bendamustine and rituximab, but bendamustine and rituximab with ibrutinib.”
“This is very exciting for our CLL patients, who have a chronic cancer; all of them will relapse and recur,” noted Dr. Merry-Jennifer Markham, an ASCO Expert from the Division of Hematology & Oncology, University of Florida in Gainesville. “We have lots of options for treatment, but the results of this combination are so exciting for them. I think this is really going to be an important drug in combination with an established chemotherapy regimen. It will really help these patients live longer, and longer lives with better quality.”
Signaling through the BTK pathway plays a critical role in the survival and proliferation of CLL cells, making treatment with ibrutinib especially attractive, according to Dr. Chanan-Khan. Results of the sister RESONATE trial established that the drug performed well when given as monotherapy to patients with relapsed or refractory CLL (N. Engl. J. Med. 2014 ;371:213-2).
Last year, the U.S. Food and Drug Administration granted accelerated approval to ibrutinib for treating CLL in patients who have already received other treatments.
In the new, Janssen-funded trial, 578 patients with CLL or small lymphocytic lymphoma, excluding those with the 17p deletion, were randomized evenly to receive ibrutinib (brand name Imbruvica) or placebo, each in addition to bendamustine (Treanda) and rituximab (Rituxan). On the basis of the sister trial’s data, the protocol was amended after the trial began to allow placebo patients to cross over to ibrutinib at the time of progression, noted Dr. Chanan-Khan.
The preplanned interim analysis, conducted after a median follow-up of 17 months, showed that median progression-free survival – the trial’s primary endpoint – was 13.3 months in the placebo group, whereas this landmark had not been reached in the ibrutinib group (hazard ratio, 0.20; P < .0001). Benefit was similar in the subgroup of patients with high-risk features.
Ibrutinib was also associated with a near-significant improvement in overall survival relative to placebo (HR, 0.63; P = .0598), a noteworthy finding as roughly a third of patients in the placebo arm had crossed over to the drug at progression, Dr. Chanan-Khan pointed out. The ibrutinib group had a superior overall response rate as well (82.7% vs. 67.8%; P < .0001).
“The side effect profile was very tolerable and expected for each of the individual drugs that were in this regimen,” he reported. The most common side effects – neutropenia, thrombocytopenia, diarrhea, and nausea – occurred in similar proportions in each group.
With respect to side effects known to be specific to ibrutinib, bleeding of any grade occurred in 31% of patients given the drug, compared with 17% given placebo, and serious bleeding occurred in 3.8%. Atrial fibrillation occurred in 7% with the drug, compared with 0.7% with placebo, but the proportion developing grade 3 or 4 atrial fibrillation was only about 2%.
As for future research, the investigators plan to evaluate ibrutinib alone and in combination with drugs targeting the CD20 protein in patients with newly diagnosed symptomatic and asymptomatic CLL.
Dr. Chanan-Khan reported having no financial disclosures. The trial was funded by Janssen.
AT ASCO 2015
Key clinical point: Ibrutinib prolongs progression-free survival in patients with relapsed CLL when added to chemoimmunotherapy.
Major finding: The risk of progression or death was 80% lower with addition of ibrutinib vs. placebo to bendamustine and rituximab.
Data source: An interim analysis of a randomized phase III trial in 578 patients with relapsed CLL.
Disclosures: Dr. Chanan-Khan reported having no financial disclosures. The trial was funded by Janssen.
Drug improves upon standard therapy for relapsed CLL/SLL, speaker says
Chanan-Khan, MD
© ASCO/Zach Boyden-Holmes
CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.
There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.
“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.
Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.
The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.
Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.
“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”
Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).
Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.
Response and survival
The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).
At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).
“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”
Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.
The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.
The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).
Adverse events
Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.
The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).
The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).
Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.
The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.
Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.
Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.
“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”
Chanan-Khan, MD
© ASCO/Zach Boyden-Holmes
CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.
There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.
“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.
Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.
The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.
Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.
“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”
Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).
Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.
Response and survival
The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).
At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).
“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”
Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.
The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.
The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).
Adverse events
Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.
The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).
The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).
Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.
The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.
Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.
Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.
“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”
Chanan-Khan, MD
© ASCO/Zach Boyden-Holmes
CHICAGO—Interim results of the phase 3 HELIOS trial suggest that adding ibrutinib to treatment with bendamustine and rituximab (BR) improves outcomes for patients with relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Patients who received ibrutinib and BR had significantly higher response rates and a significantly longer progression-free survival than patients who received BR with placebo.
There was no significant difference between the arms with regard to overall survival, but the researchers said these results were confounded by the fact that 31% of patients in the placebo arm crossed over to the ibrutinib arm after they progressed.
“We found that ibrutinib can be safely paired with existing therapy to powerfully prolong remissions and improve patients’ well-being,” said study investigator Asher Alban Akmal Chanan-Khan, MD, of the Mayo Clinic in Jacksonville, Florida.
Dr Chanan-Khan presented these findings at the 2015 ASCO Annual Meeting (abstract LBA7005). The research was funded by Janssen Research & Development, LLC, the company co-developing ibrutinib with Pharmacyclics.
The study included 578 patients with previously treated CLL/SLL, excluding those with del(17p). The patients were randomized to receive 6 cycles of BR plus once-daily ibrutinib (n=289) or 6 cycles of BR plus placebo (n=289). Ibrutinib and placebo were given until disease progression or unacceptable toxicity.
Dr Chanan-Khan said baseline characteristics were comparable between the treatment arms. For each arm, the median number of prior treatments was 2, more than 50% of patients had bulky disease, and about 80% of patients had unmutated IGVH.
“[However,] advanced Rai-stage disease was observed in a slightly [greater] proportion of patients in the control arm versus the ibrutinib arm,” Dr Chanan-Khan noted. “Conversely, a higher proportion of patients with del(11q) was noted in the ibrutinib-containing arm.”
Ultimately, 81.9% (n=235) of patients in the ibrutinib arm and 77.4% (n=222) of those in the placebo arm received their assigned 6 cycles of BR. At the time of analysis, the rate of treatment discontinuation was 29.1% (n=84) in the ibrutinib arm and 64.7% in the placebo arm (n=187).
Those patients who progressed on placebo were allowed to cross over to the ibrutinib arm, and 90 patients had crossed over at the time of the interim analysis.
Response and survival
The study’s primary endpoint was progression-free survival, as assessed by an independent review committee (IRC), in the intent-to-treat population (n=289 in each arm).
At a median follow-up of 17 months, progression-free survival was 13.3 months in the placebo arm and was not reached in the ibrutinib arm (P<0.0001).
“The hazard ratio on this particular survival curve is 0.20, which translates into a reduced risk of progression or death by 80%,” Dr Chanan-Khan said. “This is remarkable. You cannot get a better hazard ratio than this.”
Dr Chanan-Khan also noted that the overall response rate was significantly higher in the ibrutinib arm than the placebo arm. The rates were 82.7% and 67.8%, respectively (P<0.0001), according to the IRC, and 86.2% and 68.9%, respectively (P<0.0001), according to investigator assessment.
The rate of complete response plus complete response with incomplete blood count recovery was 10.4% in the ibrutinib arm and 2.8% in the placebo arm, according to the IRC. According to investigator assessment, the rates were 21.4% and 5.9%, respectively.
The median overall survival was not reached in either arm, and the hazard ratio was 0.628 (P=0.0598).
Adverse events
Dr Chanan-Kahn said the safety profile of the ibrutinib-BR combination was consistent with the safety profiles of each individual drug.
The incidence of adverse events was 70.7% in the ibrutinib-BR arm and 70% in the placebo-BR arm. The most common events were neutropenia (58.2% and 54.7%, respectively), nausea (36.9% vs 35.2%), diarrhea (35.5% vs 23.7%), thrombocytopenia (30.7% vs 24.4%), pyrexia (24.7% vs 22%), anemia (22.6% vs 28.9%), and fatigue (21.6% vs 22.6%).
The incidence of grade 3/4 adverse events was 28.9% in the ibrutinib arm and 25% in the placebo arm. The most common of these were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15% in both arms).
Atrial fibrillation was seen in 7.3% of patients in the ibrutinib arm and 2.8% in the placebo arm. Grade 3/4 atrial fibrillation occurred in 2.8% and 0.7% of patients, respectively. The incidence of tumor lysis syndrome was 3.5% in both arms.
The rate of bleeding was 31% in the ibrutinib arm and 14.6% in the placebo arm. And the rates of major hemorrhage were 3.8% and 1.7%, respectively.
Adverse events were the primary reason for discontinuation in patients who received ibrutinib—14.2%, compared to 11.8% of patients who received placebo. The primary reason for discontinuation in the placebo arm was progressive disease or relapse—45%, compared to 4.8% in the ibrutinib arm.
Taken together, the results of this trial suggest treatment with ibrutinib and BR is superior to standard BR therapy in patients with relapsed CLL/SLL, Dr Chanan-Kahn said.
“This was one of the most rigorous clinical trials ever conducted in CLL,” he said, “and it truly validates ibrutinib as an important drug for this cancer.”
VIDEO: Nivolumab puts brakes on advanced liver cancer
CHICAGO – Immune checkpoint inhibition with nivolumab every 2 weeks provides a better response than does standard treatment for advanced liver cancer, phase I/II results suggest.
The overall response rate was 19%, with 8 of the 42 evaluable patients experiencing at least 30% tumor shrinkage.
Moreover, responses to nivolumab (Opdivo) have been durable, with 62% of patients still alive at 12 months, Dr. Anthony El-Khoueiry reported in a press briefing in advance of the formal presentation of the study at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In contrast, just 2% of patients have at least 30% tumor shrinkage with sorafenib (Nexavar) and the average overall survival is about 10-11 months. Sorafenib, a multitargeted tyrosine kinase inhibitor, is currently the only Food and Drug Administration–approved systemic treatment for advanced liver disease, he noted.
Nivolumab, a programmed death-1 (PD-1) inhibitor, is approved for previously treated melanoma and gained a second indication in March for use in previously treated squamous non–small cell lung cancer.
“This is the first study to show antitumor activity of a PD-1 immune checkpoint inhibitor in patients with liver cancer,” said Dr. El-Khoueiry of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles.The durability of those responses was particularly impressive, Dr. Peter Paul Yu, ASCO president, said in an interview.
“This is a small study, but the signal is unusually robust in comparison to what the standard of care would be, which is why this is so promising,” he added.
Press briefing moderator Dr. Lynn Schuchter, chief of hematology-oncology at University of Pennsylvania in Philadelphia, said in a statement, “The fact that this drug might stop advanced liver cancer in its tracks for months, even a year, is great news for patients. To understand the full impact of this approach, however, larger trials are needed.”
Hear more about the promising results from the late-breaking abstract in our interview with Dr. El-Khoueiry.
The study was funded by Bristol-Myers Squibb. Dr. El-Khoueiry reported financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech/Roche, Amgen, Exelixis, AstraZeneca, and Astex Pharmaceuticals. Several coauthors also had ties to BMS including employment and/or stock ownership. Dr. Schuchter reported institutional research funding from BMS, Genentech, GSK, Merck, and Roche.
On Twitter @pwendl
CHICAGO – Immune checkpoint inhibition with nivolumab every 2 weeks provides a better response than does standard treatment for advanced liver cancer, phase I/II results suggest.
The overall response rate was 19%, with 8 of the 42 evaluable patients experiencing at least 30% tumor shrinkage.
Moreover, responses to nivolumab (Opdivo) have been durable, with 62% of patients still alive at 12 months, Dr. Anthony El-Khoueiry reported in a press briefing in advance of the formal presentation of the study at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In contrast, just 2% of patients have at least 30% tumor shrinkage with sorafenib (Nexavar) and the average overall survival is about 10-11 months. Sorafenib, a multitargeted tyrosine kinase inhibitor, is currently the only Food and Drug Administration–approved systemic treatment for advanced liver disease, he noted.
Nivolumab, a programmed death-1 (PD-1) inhibitor, is approved for previously treated melanoma and gained a second indication in March for use in previously treated squamous non–small cell lung cancer.
“This is the first study to show antitumor activity of a PD-1 immune checkpoint inhibitor in patients with liver cancer,” said Dr. El-Khoueiry of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles.The durability of those responses was particularly impressive, Dr. Peter Paul Yu, ASCO president, said in an interview.
“This is a small study, but the signal is unusually robust in comparison to what the standard of care would be, which is why this is so promising,” he added.
Press briefing moderator Dr. Lynn Schuchter, chief of hematology-oncology at University of Pennsylvania in Philadelphia, said in a statement, “The fact that this drug might stop advanced liver cancer in its tracks for months, even a year, is great news for patients. To understand the full impact of this approach, however, larger trials are needed.”
Hear more about the promising results from the late-breaking abstract in our interview with Dr. El-Khoueiry.
The study was funded by Bristol-Myers Squibb. Dr. El-Khoueiry reported financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech/Roche, Amgen, Exelixis, AstraZeneca, and Astex Pharmaceuticals. Several coauthors also had ties to BMS including employment and/or stock ownership. Dr. Schuchter reported institutional research funding from BMS, Genentech, GSK, Merck, and Roche.
On Twitter @pwendl
CHICAGO – Immune checkpoint inhibition with nivolumab every 2 weeks provides a better response than does standard treatment for advanced liver cancer, phase I/II results suggest.
The overall response rate was 19%, with 8 of the 42 evaluable patients experiencing at least 30% tumor shrinkage.
Moreover, responses to nivolumab (Opdivo) have been durable, with 62% of patients still alive at 12 months, Dr. Anthony El-Khoueiry reported in a press briefing in advance of the formal presentation of the study at the annual meeting of the American Society of Clinical Oncology.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
In contrast, just 2% of patients have at least 30% tumor shrinkage with sorafenib (Nexavar) and the average overall survival is about 10-11 months. Sorafenib, a multitargeted tyrosine kinase inhibitor, is currently the only Food and Drug Administration–approved systemic treatment for advanced liver disease, he noted.
Nivolumab, a programmed death-1 (PD-1) inhibitor, is approved for previously treated melanoma and gained a second indication in March for use in previously treated squamous non–small cell lung cancer.
“This is the first study to show antitumor activity of a PD-1 immune checkpoint inhibitor in patients with liver cancer,” said Dr. El-Khoueiry of the University of Southern California Norris Comprehensive Cancer Center, Los Angeles.The durability of those responses was particularly impressive, Dr. Peter Paul Yu, ASCO president, said in an interview.
“This is a small study, but the signal is unusually robust in comparison to what the standard of care would be, which is why this is so promising,” he added.
Press briefing moderator Dr. Lynn Schuchter, chief of hematology-oncology at University of Pennsylvania in Philadelphia, said in a statement, “The fact that this drug might stop advanced liver cancer in its tracks for months, even a year, is great news for patients. To understand the full impact of this approach, however, larger trials are needed.”
Hear more about the promising results from the late-breaking abstract in our interview with Dr. El-Khoueiry.
The study was funded by Bristol-Myers Squibb. Dr. El-Khoueiry reported financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Genentech/Roche, Amgen, Exelixis, AstraZeneca, and Astex Pharmaceuticals. Several coauthors also had ties to BMS including employment and/or stock ownership. Dr. Schuchter reported institutional research funding from BMS, Genentech, GSK, Merck, and Roche.
On Twitter @pwendl
AT THE ASCO ANNUAL MEETING 2015
