Meeting Highlights
American Society of Clinical Oncology Walter Alexander The American Society of Clinical Oncology (ASCO) 2015 Annual Meeting, held from May 29 to June 2 in Chicago, Illinois, hosted approximately 30,000 medical professionals, about half of them international attendees. We review key research findings in therapies for renal cell carcinoma, prostate cancer, melanoma, myelofibrosis, multiple myeloma, and chronic lymphocytic leukemia.
RECORD-4: A Multicenter, Phase II Trial of Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma • Robert J. Motzer, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York, New York The RECORD-1 trial showed everolimus to be superior to placebo in patients with metastatic renal cell carcinoma (mRCC) who had been treated previously with sunitinib, sorafenib, or both or with cytokines, bevacizumab, and other chemotherapy. RECORD-4 results reinforced those findings for everolimus in second-line treatment of mRCC. In RECORD-1, median progression-free survival (PFS) was 4.9 months with everolimus and 1.9 months with placebo (hazard ratio [HR], 0.33; P < 0.001). Subanalysis showed longer median PFS in patients who had received one vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFR-TKI) than for those who had received two VEGFRTKIs (5.4 months versus 4.0 months). RECORD-4 prospectively assessed pure second-line treatment of mRCC with everolimus among patients who had progressed after first-line treatment with an anti-VEGF or cytokine agent. Patients (n = 134) received everolimus 10 mg per day until progressive disease or intolerance. Tumor evaluations were conducted every eight weeks until documented progressive disease or initiation of third-line therapy. The primary endpoint of the open-label, multicenter, international phase 2 study was PFS. Fifty-eight patients had received first-line sunitinib and 62 had received other first-line anti-VEGF agents (bevacizumab, pazopanib, tivozanib, axitinib). Dr. Motzer reported that PFS was 7.8 months (95% confidence interval [CI], 5.7–11.0). Analysis by first-line treatment revealed PFS of 5.7 months in those who had received first-line sunitinib (n = 58), 7.8 months with other first-line VEGF therapy (n = 62), and 12.9 months with first-line cytokine therapy (n = 14). Most patients achieved stable disease (first-line sunitinib, 64%; other anti-VEGF therapy, 73%; first-line cytokine therapy, 57%). Partial responses were achieved in 7% of patients with prior sunitinib as first-line treatment, 5% with other anti-VEGF therapy, and 21% with first-line cytokine-based therapy. Consistent with RECORD-1, rates of grade 3–4 adverse events (AEs) were 55%, 52%, and 71% for prior sunitinib, other antiThe author is a freelance medical writer living in New York City.
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VEGF therapies, and cytokine-based therapies, respectively. Thirteen on-treatment deaths occurred. “RECORD-4 results confirm the progression-free survival benefit with everolimus in a second-line setting,” Dr. Motzer concluded. ASCO discussant Bernard Escudier, MD, of Gustave Roussy in Villejuif, France, agreed: “Progression-free survival observed in RECORD-4 confirms the efficacy of everolimus in the second-line setting.”
A Phase III Protocol of Androgen Suppression And 3DCRT/IMRT Versus AS and 3DCRT/IMRT Followed by Chemotherapy With Docetaxel and Prednisone for Localized, High-Risk Prostate Cancer (RTOG 0521)
• Howard Sandler, MD, Chair, Department of Radiation Oncology, Cedars-Sinai, Los Angeles, California For the first time, improvements in overall survival (OS) were reported in localized, high-risk, hormone-sensitive prostate cancer with a tolerable adjuvant chemotherapy regimen, Dr. Sandler said. Generally, the prognosis for this population is relatively poor. Standard management often includes radiation and long-term hormonal treatment (two to three years). Dr. Sandler hypothesized that adding chemotherapy to radiation therapy would be beneficial for patients with nonmetastatic hormone-sensitive prostate cancer. Docetaxel chemotherapy had already been shown to be beneficial in metastatic hormone-resistant prostate cancer. Patients were assigned to one of two arms: the first receiving androgen suppression for 24 months and external radiotherapy (75.6 Gy) for eight weeks, and the second receiving the same therapy plus six cycles of docetaxel (75 mg/m2 on day 1 of six 21-day cycles plus prednisone 10 mg daily) beginning four weeks after radiotherapy. The primary endpoint was OS. About half of the 563 evaluable patients had Gleason scores of 9–10, with prostate-specific antigen of 150 or less and any tumor stage. Patients’ median age was 66 years. “This was a subset of very high-risk prostate cancer patients,” Dr. Sandler said. Four-year OS was 89% without docetaxel and 93% with docetaxel (HR, 0.79; 90% CI, 0.51–0.98, P = 0.04) after a median follow-up of six years. Distant metastases were detected in 26 patients receiving docetaxel and in 41 patients in the arm without docetaxel (P = 0.05). Blinded central review reported 16 cancer-related deaths in the docetaxel arm and 23 in the arm without docetaxel. The docetaxel arm had higher rates of grade 3–5 events that were deemed definitely, probably, or possibly related to treatment (65% versus 22%). “I believe these results are clinically relevant,” said press conference moderator Don S. Dizon, MD, of Massachusetts General Hospital in Boston, “with wide implications, especially for those diagnosed with high-risk, locally advanced prostate cancer.” Dr. Sandler noted that the findings were consistent with those reported for the STAMPEDE and CHAARTED trials. “Longer-term follow-up will likely be enlightening,” he added.
Meeting Highlights: American Society of Clinical Oncology Efficacy and Safety Results From a Phase III Trial of Nivolumab Alone or Combined With Ipilimumab Versus Ipilimumab Alone in Treatment-Naive Patients With Advanced Melanoma (CheckMate 067)
ing moderator Jyoti Patel, MD, of the Northwestern University Feinberg School of Medicine in Chicago.
• Jedd D. Wolchok, MD, Chief, Melanoma and Immuno therapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York
• Ruben A. Mesa, MD, Chair, Hematology, Mayo Clinic Cancer Center, Scottsdale, Arizona
Results of the phase 3 CheckMate 067 trial showed strong efficacy with manageable toxicity for the combination of nivolumab and ipilimumab in advanced melanoma. PFS was numerically longer and the overall response rate (ORR) was significantly higher for the combination than for ipilimumab alone. The incidence of AEs, while higher for the combination, was consistent with earlier experience, Dr. Wolchok said at an ASCO press briefing. The checkpoint inhibitors represent two distinct and complementary pathways that negatively regulate tumor immunity. Ipilimumab as monotherapy improves OS in melanoma, with about 20% of patients alive after three or more years. Phase 2 studies of nivolumab monotherapy have demonstrated one-year survival rates of 73% and ORRs of 40% in untreated melanoma (BRAF wild-type). In patients who had progressed after treatment with ipilimumab (or ipilimumab plus a BRAF inhibitor in BRAF mutation-positive patients), the ORR with nivolumab was 32%. Furthermore, in a phase 2 study of nivolumab plus ipilimumab in untreated melanoma, the ORR was high at 59% (11% for ipilimumab alone) and the complete response rate was 22%. Programmed death ligand 1 (PD-L1) expression did not affect response rates. CheckMate 067, conducted at 137 sites globally, is the first phase 3 evaluation of the combination. It included 945 treatmentnaïve patients with unresectable stage III or IV melanoma. They were randomized 1:1:1 to nivolumab 1 mg/kg every two weeks plus ipilimumab 3 mg/kg every three weeks for four doses followed by nivolumab 3 mg/kg every two weeks; nivolumab 3 mg/kg every two weeks plus placebo; or ipilimumab 3 mg/kg every three weeks for four doses plus placebo, until progression or unacceptable toxicity. The coprimary endpoints were PFS and OS (data not yet mature). Patients’ median age was 61 years; approximately 65% were male. PD-L1 expression was 5% or greater in approximately 24% of patients. PFS in the intent-to-treat population was 11.5 months for the combination, 6.9 months for nivolumab alone, and 2.9 months for ipilimumab alone. The HR for nivolumab/ ipilimumab versus ipilimumab was 0.42 (P
American Society of Clinical Oncology Walter Alexander The American Society of Clinical Oncology (ASCO) 2015 Annual Meeting, held from May 29 to June 2 in Chicago, Illinois, hosted approximately 30,000 medical professionals, about half of them international attendees. We review key research findings in therapies for renal cell carcinoma, prostate cancer, melanoma, myelofibrosis, multiple myeloma, and chronic lymphocytic leukemia.
RECORD-4: A Multicenter, Phase II Trial of Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma • Robert J. Motzer, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York, New York The RECORD-1 trial showed everolimus to be superior to placebo in patients with metastatic renal cell carcinoma (mRCC) who had been treated previously with sunitinib, sorafenib, or both or with cytokines, bevacizumab, and other chemotherapy. RECORD-4 results reinforced those findings for everolimus in second-line treatment of mRCC. In RECORD-1, median progression-free survival (PFS) was 4.9 months with everolimus and 1.9 months with placebo (hazard ratio [HR], 0.33; P < 0.001). Subanalysis showed longer median PFS in patients who had received one vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFR-TKI) than for those who had received two VEGFRTKIs (5.4 months versus 4.0 months). RECORD-4 prospectively assessed pure second-line treatment of mRCC with everolimus among patients who had progressed after first-line treatment with an anti-VEGF or cytokine agent. Patients (n = 134) received everolimus 10 mg per day until progressive disease or intolerance. Tumor evaluations were conducted every eight weeks until documented progressive disease or initiation of third-line therapy. The primary endpoint of the open-label, multicenter, international phase 2 study was PFS. Fifty-eight patients had received first-line sunitinib and 62 had received other first-line anti-VEGF agents (bevacizumab, pazopanib, tivozanib, axitinib). Dr. Motzer reported that PFS was 7.8 months (95% confidence interval [CI], 5.7–11.0). Analysis by first-line treatment revealed PFS of 5.7 months in those who had received first-line sunitinib (n = 58), 7.8 months with other first-line VEGF therapy (n = 62), and 12.9 months with first-line cytokine therapy (n = 14). Most patients achieved stable disease (first-line sunitinib, 64%; other anti-VEGF therapy, 73%; first-line cytokine therapy, 57%). Partial responses were achieved in 7% of patients with prior sunitinib as first-line treatment, 5% with other anti-VEGF therapy, and 21% with first-line cytokine-based therapy. Consistent with RECORD-1, rates of grade 3–4 adverse events (AEs) were 55%, 52%, and 71% for prior sunitinib, other antiThe author is a freelance medical writer living in New York City.
526 P&T • ®
August 2015 • Vol. 40 No. 8
VEGF therapies, and cytokine-based therapies, respectively. Thirteen on-treatment deaths occurred. “RECORD-4 results confirm the progression-free survival benefit with everolimus in a second-line setting,” Dr. Motzer concluded. ASCO discussant Bernard Escudier, MD, of Gustave Roussy in Villejuif, France, agreed: “Progression-free survival observed in RECORD-4 confirms the efficacy of everolimus in the second-line setting.”
A Phase III Protocol of Androgen Suppression And 3DCRT/IMRT Versus AS and 3DCRT/IMRT Followed by Chemotherapy With Docetaxel and Prednisone for Localized, High-Risk Prostate Cancer (RTOG 0521)
• Howard Sandler, MD, Chair, Department of Radiation Oncology, Cedars-Sinai, Los Angeles, California For the first time, improvements in overall survival (OS) were reported in localized, high-risk, hormone-sensitive prostate cancer with a tolerable adjuvant chemotherapy regimen, Dr. Sandler said. Generally, the prognosis for this population is relatively poor. Standard management often includes radiation and long-term hormonal treatment (two to three years). Dr. Sandler hypothesized that adding chemotherapy to radiation therapy would be beneficial for patients with nonmetastatic hormone-sensitive prostate cancer. Docetaxel chemotherapy had already been shown to be beneficial in metastatic hormone-resistant prostate cancer. Patients were assigned to one of two arms: the first receiving androgen suppression for 24 months and external radiotherapy (75.6 Gy) for eight weeks, and the second receiving the same therapy plus six cycles of docetaxel (75 mg/m2 on day 1 of six 21-day cycles plus prednisone 10 mg daily) beginning four weeks after radiotherapy. The primary endpoint was OS. About half of the 563 evaluable patients had Gleason scores of 9–10, with prostate-specific antigen of 150 or less and any tumor stage. Patients’ median age was 66 years. “This was a subset of very high-risk prostate cancer patients,” Dr. Sandler said. Four-year OS was 89% without docetaxel and 93% with docetaxel (HR, 0.79; 90% CI, 0.51–0.98, P = 0.04) after a median follow-up of six years. Distant metastases were detected in 26 patients receiving docetaxel and in 41 patients in the arm without docetaxel (P = 0.05). Blinded central review reported 16 cancer-related deaths in the docetaxel arm and 23 in the arm without docetaxel. The docetaxel arm had higher rates of grade 3–5 events that were deemed definitely, probably, or possibly related to treatment (65% versus 22%). “I believe these results are clinically relevant,” said press conference moderator Don S. Dizon, MD, of Massachusetts General Hospital in Boston, “with wide implications, especially for those diagnosed with high-risk, locally advanced prostate cancer.” Dr. Sandler noted that the findings were consistent with those reported for the STAMPEDE and CHAARTED trials. “Longer-term follow-up will likely be enlightening,” he added.
Meeting Highlights: American Society of Clinical Oncology Efficacy and Safety Results From a Phase III Trial of Nivolumab Alone or Combined With Ipilimumab Versus Ipilimumab Alone in Treatment-Naive Patients With Advanced Melanoma (CheckMate 067)
ing moderator Jyoti Patel, MD, of the Northwestern University Feinberg School of Medicine in Chicago.
• Jedd D. Wolchok, MD, Chief, Melanoma and Immuno therapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York
• Ruben A. Mesa, MD, Chair, Hematology, Mayo Clinic Cancer Center, Scottsdale, Arizona
Results of the phase 3 CheckMate 067 trial showed strong efficacy with manageable toxicity for the combination of nivolumab and ipilimumab in advanced melanoma. PFS was numerically longer and the overall response rate (ORR) was significantly higher for the combination than for ipilimumab alone. The incidence of AEs, while higher for the combination, was consistent with earlier experience, Dr. Wolchok said at an ASCO press briefing. The checkpoint inhibitors represent two distinct and complementary pathways that negatively regulate tumor immunity. Ipilimumab as monotherapy improves OS in melanoma, with about 20% of patients alive after three or more years. Phase 2 studies of nivolumab monotherapy have demonstrated one-year survival rates of 73% and ORRs of 40% in untreated melanoma (BRAF wild-type). In patients who had progressed after treatment with ipilimumab (or ipilimumab plus a BRAF inhibitor in BRAF mutation-positive patients), the ORR with nivolumab was 32%. Furthermore, in a phase 2 study of nivolumab plus ipilimumab in untreated melanoma, the ORR was high at 59% (11% for ipilimumab alone) and the complete response rate was 22%. Programmed death ligand 1 (PD-L1) expression did not affect response rates. CheckMate 067, conducted at 137 sites globally, is the first phase 3 evaluation of the combination. It included 945 treatmentnaïve patients with unresectable stage III or IV melanoma. They were randomized 1:1:1 to nivolumab 1 mg/kg every two weeks plus ipilimumab 3 mg/kg every three weeks for four doses followed by nivolumab 3 mg/kg every two weeks; nivolumab 3 mg/kg every two weeks plus placebo; or ipilimumab 3 mg/kg every three weeks for four doses plus placebo, until progression or unacceptable toxicity. The coprimary endpoints were PFS and OS (data not yet mature). Patients’ median age was 61 years; approximately 65% were male. PD-L1 expression was 5% or greater in approximately 24% of patients. PFS in the intent-to-treat population was 11.5 months for the combination, 6.9 months for nivolumab alone, and 2.9 months for ipilimumab alone. The HR for nivolumab/ ipilimumab versus ipilimumab was 0.42 (P
