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
Journal
Journal of Clinical Oncology
Journal Volume
31
Journal Issue
31
Pages
3926-3934
Date Issued
2013
Author(s)
Johnson B.E
Kabbinavar F
Fehrenbacher L
Hainsworth J
Kasubhai S
Kressel B
Lin C.-Y
Marsland T
Patel T
Polikoff J
Rubin M
White L
Bowden C
Miller V.
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. ? 2013 by American Society of Clinical Oncology.
SDGs
Other Subjects
antineoplastic agent; bevacizumab; carboplatin; cisplatin; docetaxel; erlotinib; gemcitabine; paclitaxel; placebo; antineoplastic agent; bevacizumab; erlotinib; monoclonal antibody; quinazoline derivative; antineoplastic agent; monoclonal antibody; quinazoline derivative; add on therapy; adenocarcinoma; adult; advanced cancer; aged; arterial thromboembolism; article; atlas; blindness; cancer combination chemotherapy; cancer growth; cancer patient; cancer recurrence; cancer staging; cancer survival; cardiovascular symptom; controlled study; cytodiagnosis; diarrhea; digestive system perforation; disease severity; double blind procedure; drug dose reduction; drug efficacy; drug eruption; drug safety; drug tolerability; drug withdrawal; female; follow up; histopathology; human; hypertension; infection; interstitial lung disease; kidney failure; large cell carcinoma; lung hemorrhage; lung non small cell cancer; maintenance therapy; major clinical study; male; malignant pleura effusion; middle aged; monotherapy; multiple cycle treatment; outcome assessment; overall survival; phase 3 clinical trial; posterior reversible encephalopathy syndrome; priority journal; progression free survival; proteinuria; randomized controlled trial; squamous cell carcinoma; survival time; treatment duration; unspecified side effect; venous thromboembolism; very elderly; young adult; controlled clinical trial; disease free survival; Kaplan Meier method; lung non small cell cancer; lung tumor; maintenance chemotherapy; methodology; mortality; multicenter study; proportional hazards model; treatment outcome; Carcinoma, Non-Small-Cell Lung; clinical trial; Lung Neoplasms; maintenance chemotherapy; procedures; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Maintenance Chemotherapy; Male; Middle Aged; Proportional Hazards Models; Quinazolines; Treatment Outcome; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Maintenance Chemotherapy; Male; Middle Aged; Proportional Hazards Models; Quinazolines; Treatment Outcome
Publisher
American Society of Clinical Oncology
Type
journal article