ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing
bevacizumab therapy with or without erlotinib, after completion of chemotherapy,
with bevacizumab for first-line treatment of advanced non-small-cell lung cancer.
Author(s): Johnson BE(1), Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B,
Lin CY, Marsland T, Patel T, Polikoff J, Rubin M, White L, Yang JC, Bowden C,
Miller V.
Affiliation(s): Author information:
(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.
Publication date & source: 2013, J Clin Oncol. , 31(31):3926-34
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.
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