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.

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.

• Authors: Bruce E Johnson, 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 31 Pg. 3926-34 (Nov 01 2013) ISSN: 1527-7755 [Electronic] United States
• PMID: 24101054 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Quinazolines
• Bevacizumab
• Erlotinib Hydrochloride

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality)
• Disease-Free Survival
• Double-Blind Method
• Erlotinib Hydrochloride
• Female
• Humans
• Kaplan-Meier Estimate
• Lung Neoplasms (drug therapy, mortality)
• Maintenance Chemotherapy (methods)
• Male
• Middle Aged
• Proportional Hazards Models
• Quinazolines (administration & dosage, adverse effects)
• Treatment Outcome