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Efficacy and Safety of Eribulin Compared with Treatment of Physician’s Choice (TPC) in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC): Results from a Phase 3 Study
International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Late-Breaking Abstracts e 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology These late-breaking abstracts were presented at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology held October 30-November 1, 2014, in Chicago, Illinois.
ORAL ABSTRACT SESSION
LB1-Locally Advanced Non-small Cell Lung Cancer Efficacy and Safety of Eribulin Compared with Treatment of Physician’s Choice (TPC) in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC): Results from a Phase 3 Study Locally Advanced Non-small Cell Lung Cancer D.R. Spigel,1 F. Barlesi,2 E. Felip,3 J. Kim,4 M. Olivo,5 H. Nokihara,6 J.C. Yang,7 M. Satouchi,8 N. Katakami,9 and N. Iannotti10; 1Sarah Cannon Institute, Nashville, TN, 2Aix Marseille University, Assistance Publique Hoˆpitaux de Marseille, Marseille, France, 3Vall d’Hebron University Hospital, Barcelona, Spain, 4Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of, 5Eisai Inc, Woodcliff Lake, NJ, 6National Cancer Center Hospital, Tokyo-to, Japan, 7National Taiwan University Hospital, Taipei, Taiwan, 8Hyogo Cancer Center, Akashi-shi, Japan, 9Institute of Biomedical Research and Innovation Hospital, Kobe-shi, Japan, 10 Hematology-Oncology Associates of Treasure Coast, Port St. Lucie, FL Purpose/Objective(s): Despite advances, options are limited for the treatment of patients who have failed two lines of therapy for advanced NSCLC. Eribulin is a microtubule dynamics inhibitor from the halichondrin class. In this phase 3 study, eribulin was compared with TPC in patients with advanced NSCLC. Materials/Methods: In this open-label, parallel-group study, patients with advanced NSCLC and disease progression following 2 prior regimens for advanced disease (including platinum-based therapy) were randomized 1:1 to receive iv eribulin mesylate (1.4 mg/m2 on days 1 and 8, every 21 days) or TPC (21-day cycles of vinorelbine, gemcitabine, pemetrexed [nonsquamous only] or docetaxel); randomization was stratified by geographic region, histology (squamous, nonsquamous) and TPC option. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety and tolerability. Results: 540 patients were randomized (eribulin, n Z 270; TPC, n Z 270). Overall, 33.3% of patients were aged > 65 years, 61.5% were male and 26.7% had never smoked; 20.9% had squamous histology, and 55.0% had received 3 prior chemotherapy regimens. Median OS was 9.5 months in both the eribulin and TPC groups (HR, 1.16 [95% CI, 0.95, 1.41]; p Z 0.134). Median PFS was 3.0 months with eribulin and 2.8 months with TPC (HR, 1.09 [95% CI, 0.90, 1.32]; p Z 0.395), and ORRs were 12.2% and 15.2% for eribulin and TPC, respectively. The most frequent grade 3/4 AEs with eribulin were neutropenia (28.6%), decreased neutrophil count (21.2%), decreased WBC count (13.4%) and asthenia (8.2%); 33.9% of patients had a serious AE (35.7% eribulin, 32.1% TPC). Conclusions: Eribulin did not improve OS or PFS compared with TPC in patients with advanced NSCLC. AEs were manageable and consistent with previous eribulin studies. Author Disclosures: D.R. Spigel: None. F. Barlesi: None. E. Felip: G. Consultant; Lilly, Roche, Boehringer Ingelheim, BMS, Novartis. J. Kim:
E. Research Grant; SIT by Roche, Lilly, Pfizer, BMS, Eisai. M. Olivo: A. Employee; Eisai Inc. H. Nokihara: E. Research Grant; Pfizer, Merck, Eisai, Taiho, Chugai, Eli Lilly, Daiichi-Sankyo, GlaxoSmithKline, Novartis. J.C. Yang: E. Research Grant; Boehringer Ingelheim, Eisai. F. Honoraria; AstraZeneca, Bayer, Roche, Abbott, Boehringer Ingelheim, Pfizer. G. Consultant; AstraZeneca, Roche, Genetech, Boehringer Ingelheim, Novartis, Takeda, Eli Lilly, Pfizer, Clovis, Merck. M. Satouchi: F. Honoraria; Eli Lilly Japan, Kyowa Hakko Kirin, Sanofi, Nippon Kayaku. N. Katakami: E. Research Grant; Eisai. N. Iannotti: None.
PLENARY SESSION
LB2-Metastatic Non-small Cell Lung Cancer Phase II Study of Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in Patients with Advanced, Refractory Squamous Non-Small Cell Lung Cancer Metastatic Non-small Cell Lung Cancer S.S. Ramalingam,1 J. Mazie`res,2 D. Planchard,3 T.E. Stinchcombe,4 G.K. Dy,5 S.J. Antonia,6 L. Horn,7 H. Lena,8 E. Minenza,9 B. Mennecier,10 G.A. Otterson,11 L.T. Campos,12 D.R. Gandara,13 B.P. Levy,14 S.G. Nair,15 G. Zalcman,16 J. Wolf,17 C. Baudelet,18 B.J. Lestini,19 and N.A. Rizvi20; 1 Winship Cancer Institute, Emory University, Atlanta, GA, 2Hoˆpital Larrey, Centre Hospitalier Universitaire de Toulouse, Toulouse, France, 3Gustave Roussy, Villejuif, France, 4University of North Carolina School of Medicine, Chapel Hill, NC, 5Roswell Park Cancer Institute, Buffalo, NY, 6H. Lee Moffitt Cancer Center, Tampa, FL, 7Vanderbilt Ingram Cancer Center, Nashville, TN, 8Centre Hospitalier Universitaire de Rennes, Rennes, France, 9 Ospedale S. Maria, Terni, Italy, 10Nouvel Hoˆpital Civil Chru de Strasbourg, Strasbourg, France, 11The Ohio State University Medical Center, Columbus, OH, 12Oncology Consultants, PA, Houston, TX, 13University of California Davis Cancer Center, Sacramento, CA, 14Beth Israel Comprehensive Cancer Center, New York, NY, 15Lehigh Valley Hospital, Allentown, PA, 16Centre Hospitalier Universitaire de Caen, Caen, France, 17Universitaetsklinik Koeln, Koeln, Germany, 18Bristol-Myers Squibb, Braine-I’Alleud, Belgium, 19 Bristol-Myers Squibb, Princeton, NJ, 20Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): The prognosis for patients (pts) with squamous (SQ) non-small cell lung cancer (NSCLC) who have progressed after treatment with 2 or more chemotherapy regimens is poor (response rates of 2-8% and median overall survival [OS] of about 5 mo). The efficacy of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune checkpoint inhibitor antibody, was evaluated in pts with advanced-stage refractory SQ NSCLC in a phase II, single-arm study. Materials/Methods: Pts with SQ NSCLC and progression following platinum doublet-based chemotherapy and at least 1 additional systemic therapy, ECOG performance status of 0-1, and the presence of measureable disease were eligible. Nivolumab monotherapy was administered at 3 mg/kg every 2 wk until progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR), as assessed by an independent radiology review committee (IRC) using RECIST 1.1. Secondary and exploratory objectives included investigator-assessed ORR, safety, progression-free survival (PFS), activity by PD-L1 expression status, and OS. Results: Of 117 treated patients (median age 65 y [range: 37-87], 73% male, 85% Caucasian), 65% had received 3 or more prior systemic
Radiation Oncology biology
physics
www.redjournal.org
Late-Breaking Abstracts e 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology These late-breaking abstracts were presented at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology held October 30-November 1, 2014, in Chicago, Illinois.
ORAL ABSTRACT SESSION
LB1-Locally Advanced Non-small Cell Lung Cancer Efficacy and Safety of Eribulin Compared with Treatment of Physician’s Choice (TPC) in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC): Results from a Phase 3 Study Locally Advanced Non-small Cell Lung Cancer D.R. Spigel,1 F. Barlesi,2 E. Felip,3 J. Kim,4 M. Olivo,5 H. Nokihara,6 J.C. Yang,7 M. Satouchi,8 N. Katakami,9 and N. Iannotti10; 1Sarah Cannon Institute, Nashville, TN, 2Aix Marseille University, Assistance Publique Hoˆpitaux de Marseille, Marseille, France, 3Vall d’Hebron University Hospital, Barcelona, Spain, 4Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of, 5Eisai Inc, Woodcliff Lake, NJ, 6National Cancer Center Hospital, Tokyo-to, Japan, 7National Taiwan University Hospital, Taipei, Taiwan, 8Hyogo Cancer Center, Akashi-shi, Japan, 9Institute of Biomedical Research and Innovation Hospital, Kobe-shi, Japan, 10 Hematology-Oncology Associates of Treasure Coast, Port St. Lucie, FL Purpose/Objective(s): Despite advances, options are limited for the treatment of patients who have failed two lines of therapy for advanced NSCLC. Eribulin is a microtubule dynamics inhibitor from the halichondrin class. In this phase 3 study, eribulin was compared with TPC in patients with advanced NSCLC. Materials/Methods: In this open-label, parallel-group study, patients with advanced NSCLC and disease progression following 2 prior regimens for advanced disease (including platinum-based therapy) were randomized 1:1 to receive iv eribulin mesylate (1.4 mg/m2 on days 1 and 8, every 21 days) or TPC (21-day cycles of vinorelbine, gemcitabine, pemetrexed [nonsquamous only] or docetaxel); randomization was stratified by geographic region, histology (squamous, nonsquamous) and TPC option. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety and tolerability. Results: 540 patients were randomized (eribulin, n Z 270; TPC, n Z 270). Overall, 33.3% of patients were aged > 65 years, 61.5% were male and 26.7% had never smoked; 20.9% had squamous histology, and 55.0% had received 3 prior chemotherapy regimens. Median OS was 9.5 months in both the eribulin and TPC groups (HR, 1.16 [95% CI, 0.95, 1.41]; p Z 0.134). Median PFS was 3.0 months with eribulin and 2.8 months with TPC (HR, 1.09 [95% CI, 0.90, 1.32]; p Z 0.395), and ORRs were 12.2% and 15.2% for eribulin and TPC, respectively. The most frequent grade 3/4 AEs with eribulin were neutropenia (28.6%), decreased neutrophil count (21.2%), decreased WBC count (13.4%) and asthenia (8.2%); 33.9% of patients had a serious AE (35.7% eribulin, 32.1% TPC). Conclusions: Eribulin did not improve OS or PFS compared with TPC in patients with advanced NSCLC. AEs were manageable and consistent with previous eribulin studies. Author Disclosures: D.R. Spigel: None. F. Barlesi: None. E. Felip: G. Consultant; Lilly, Roche, Boehringer Ingelheim, BMS, Novartis. J. Kim:
E. Research Grant; SIT by Roche, Lilly, Pfizer, BMS, Eisai. M. Olivo: A. Employee; Eisai Inc. H. Nokihara: E. Research Grant; Pfizer, Merck, Eisai, Taiho, Chugai, Eli Lilly, Daiichi-Sankyo, GlaxoSmithKline, Novartis. J.C. Yang: E. Research Grant; Boehringer Ingelheim, Eisai. F. Honoraria; AstraZeneca, Bayer, Roche, Abbott, Boehringer Ingelheim, Pfizer. G. Consultant; AstraZeneca, Roche, Genetech, Boehringer Ingelheim, Novartis, Takeda, Eli Lilly, Pfizer, Clovis, Merck. M. Satouchi: F. Honoraria; Eli Lilly Japan, Kyowa Hakko Kirin, Sanofi, Nippon Kayaku. N. Katakami: E. Research Grant; Eisai. N. Iannotti: None.
PLENARY SESSION
LB2-Metastatic Non-small Cell Lung Cancer Phase II Study of Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in Patients with Advanced, Refractory Squamous Non-Small Cell Lung Cancer Metastatic Non-small Cell Lung Cancer S.S. Ramalingam,1 J. Mazie`res,2 D. Planchard,3 T.E. Stinchcombe,4 G.K. Dy,5 S.J. Antonia,6 L. Horn,7 H. Lena,8 E. Minenza,9 B. Mennecier,10 G.A. Otterson,11 L.T. Campos,12 D.R. Gandara,13 B.P. Levy,14 S.G. Nair,15 G. Zalcman,16 J. Wolf,17 C. Baudelet,18 B.J. Lestini,19 and N.A. Rizvi20; 1 Winship Cancer Institute, Emory University, Atlanta, GA, 2Hoˆpital Larrey, Centre Hospitalier Universitaire de Toulouse, Toulouse, France, 3Gustave Roussy, Villejuif, France, 4University of North Carolina School of Medicine, Chapel Hill, NC, 5Roswell Park Cancer Institute, Buffalo, NY, 6H. Lee Moffitt Cancer Center, Tampa, FL, 7Vanderbilt Ingram Cancer Center, Nashville, TN, 8Centre Hospitalier Universitaire de Rennes, Rennes, France, 9 Ospedale S. Maria, Terni, Italy, 10Nouvel Hoˆpital Civil Chru de Strasbourg, Strasbourg, France, 11The Ohio State University Medical Center, Columbus, OH, 12Oncology Consultants, PA, Houston, TX, 13University of California Davis Cancer Center, Sacramento, CA, 14Beth Israel Comprehensive Cancer Center, New York, NY, 15Lehigh Valley Hospital, Allentown, PA, 16Centre Hospitalier Universitaire de Caen, Caen, France, 17Universitaetsklinik Koeln, Koeln, Germany, 18Bristol-Myers Squibb, Braine-I’Alleud, Belgium, 19 Bristol-Myers Squibb, Princeton, NJ, 20Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): The prognosis for patients (pts) with squamous (SQ) non-small cell lung cancer (NSCLC) who have progressed after treatment with 2 or more chemotherapy regimens is poor (response rates of 2-8% and median overall survival [OS] of about 5 mo). The efficacy of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune checkpoint inhibitor antibody, was evaluated in pts with advanced-stage refractory SQ NSCLC in a phase II, single-arm study. Materials/Methods: Pts with SQ NSCLC and progression following platinum doublet-based chemotherapy and at least 1 additional systemic therapy, ECOG performance status of 0-1, and the presence of measureable disease were eligible. Nivolumab monotherapy was administered at 3 mg/kg every 2 wk until progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR), as assessed by an independent radiology review committee (IRC) using RECIST 1.1. Secondary and exploratory objectives included investigator-assessed ORR, safety, progression-free survival (PFS), activity by PD-L1 expression status, and OS. Results: Of 117 treated patients (median age 65 y [range: 37-87], 73% male, 85% Caucasian), 65% had received 3 or more prior systemic