Bruce E Johnson1, Fairooz Kabbinavar, Louis Fehrenbacher, John Hainsworth, Saifuddin Kasubhai, Bruce Kressel, Chin-Yu Lin, Thomas Marsland, Taral Patel, Jonathan Polikoff, Mark Rubin, Leonard White, James Chih-Hsin Yang, Chris Bowden, Vincent Miller. 1. Bruce E. Johnson, Dana-Farber Cancer Institute, Boston, MA; Fairooz Kabbinavar, University of California Los Angeles, Translational Oncology Research International, Los Angeles; Louis Fehrenbacher, Kaiser Permanente Northern California, Vallejo; Chin-Yu Lin and Chris Bowden, Genentech, South San Francisco; Jonathan Polikoff, Southern California Permanente Medical Group, San Diego, CA; John Hainsworth, Sarah Cannon Research Institute, Nashville, TN; Saifuddin Kasubhai, Northwest Medical Specialties, Tacoma, WA; Bruce Kressel, Sibley Memorial Hospital, Washington, DC; Thomas Marsland, Integrated Community Oncology Network, Orange Park; Mark Rubin, Florida Cancer Specialists, Fort Myers, FL; Taral Patel, The Mark H. Zangmeister Center, Columbus, OH; Leonard White, Arch Medical Services, The Center for Cancer Care and Research, Saint Louis, MO; Vincent Miller, Weill Cornell Medical College and Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY; and James Chih-Hsin Yang, National Taiwan University, Taipei, Taiwan.
Abstract
PURPOSE: This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One thousand one hundred forty-five patients with histologically or cytologically confirmed NSCLC (stage IIIB with malignant pleural effusion, stage IV, or recurrent) received four cycles of chemotherapy plus bevacizumab. Seven hundred forty-three patients without disease progression or significant toxicity were then randomly assigned (1:1) to bevacizumab (15 mg/kg, day 1, 21-day cycle) plus either placebo or erlotinib (150 mg per day). The primary end point was progression-free survival (PFS). RESULTS:Median PFS from time of random assignment was 3.7 months with bevacizumab/placebo and 4.8 months with bevacizumab/erlotinib (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86; P < .001). Median overall survival (OS) times from random assignment were 13.3 and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib, respectively (HR, 0.92; 95% CI, 0.70 to 1.21; P = .5341). During the postchemotherapy phase, there were more adverse events (AEs) overall, more grade 3 and 4 AEs (mainly rash and diarrhea), more serious AEs, and more AEs leading to erlotinib/placebo discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo arm. The incidence of AEs leading to bevacizumab discontinuation was similar in both treatment arms. CONCLUSION: The addition of erlotinib to bevacizumab significantly improved PFS but not OS. Although generally well tolerated, the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.
RCT Entities:
PURPOSE: This phase III trial was performed to assess the potential benefit of adding maintenance erlotinib to bevacizumab after a first-line chemotherapy regimen with bevacizumab for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One thousand one hundred forty-five patients with histologically or cytologically confirmed NSCLC (stage IIIB with malignant pleural effusion, stage IV, or recurrent) received four cycles of chemotherapy plus bevacizumab. Seven hundred forty-three patients without disease progression or significant toxicity were then randomly assigned (1:1) to bevacizumab (15 mg/kg, day 1, 21-day cycle) plus either placebo or erlotinib (150 mg per day). The primary end point was progression-free survival (PFS). RESULTS: Median PFS from time of random assignment was 3.7 months with bevacizumab/placebo and 4.8 months with bevacizumab/erlotinib (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86; P < .001). Median overall survival (OS) times from random assignment were 13.3 and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib, respectively (HR, 0.92; 95% CI, 0.70 to 1.21; P = .5341). During the postchemotherapy phase, there were more adverse events (AEs) overall, more grade 3 and 4 AEs (mainly rash and diarrhea), more serious AEs, and more AEs leading to erlotinib/placebo discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo arm. The incidence of AEs leading to bevacizumab discontinuation was similar in both treatment arms. CONCLUSION: The addition of erlotinib to bevacizumab significantly improved PFS but not OS. Although generally well tolerated, the modest impact on survival and increased toxicity associated with the addition of erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen will not lead to a new postchemotherapy standard of care.
Authors: A Muscella; C Vetrugno; F Biagioni; N Calabriso; M T Calierno; F Fornai; S A De Pascali; S Marsigliante; F P Fanizzi Journal: Br J Pharmacol Date: 2016-07-22 Impact factor: 8.739
Authors: Howard L West; James Moon; Antoinette J Wozniak; Philip Mack; Fred R Hirsch; Martin J Bury; Myron Kwong; Dorothy D Nguyen; Dennis F Moore; Jieling Miao; Mary Redman; Karen Kelly; David R Gandara Journal: Clin Lung Cancer Date: 2017-07-06 Impact factor: 4.785
Authors: Rana R McKay; Guillermo De Velasco; Lillian Werner; Joaquim Bellmunt; Lauren Harshman; Christopher Sweeney; Jonathan E Rosenberg; Michelle Hirsch; Sabina Signoretti; Eliezer M Van Allen; Meghara Walsh; Ulka Vaishampayan; David F McDermott; Toni K Choueiri Journal: Cancer Date: 2016-05-19 Impact factor: 6.860
Authors: Gregory A Masters; Sarah Temin; Christopher G Azzoli; Giuseppe Giaccone; Sherman Baker; Julie R Brahmer; Peter M Ellis; Ajeet Gajra; Nancy Rackear; Joan H Schiller; Thomas J Smith; John R Strawn; David Trent; David H Johnson Journal: J Clin Oncol Date: 2015-08-31 Impact factor: 44.544