Comparative Effectiveness of Carboplatin/Pemetrexed With Versus Without Bevacizumab for Advanced Nonsquamous Non–Small Cell Lung Cancer

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Background: Despite recent advances in targeted therapy and immunotherapy for advanced non–small cell lung cancer (NSCLC), carboplatin/pemetrexed/bevacizumab remains a commonly used first-line regimen. However, it is unknown whether the addition of bevacizumab to carboplatin/pemetrexed improves overall survival (OS). Materials and Methods: Using nationally representative curated electronic health record data from Flatiron Health, we performed a retrospective cohort study of patients diagnosed with advanced nonsquamous NSCLC who received ≥1 cycle of carboplatin/pemetrexed ± bevacizumab as initial systemic therapy for stage IV or metastatic/recurrent disease. The OS impact of adding bevacizumab to carboplatin/pemetrexed was assessed using a Cox proportional hazards model to adjust for age, sex, race, original tumor stage, time between diagnosis of metastatic disease and start of chemotherapy, and performance status. In a secondary analysis of patients at a single academic institution, we also adjusted for the presence of brain metastases, hemoptysis, and anticoagulation. Results: A total of 4,724 patients were included, of which 2,759 patients (58%) received carboplatin/pemetrexed and 1,965 (42%) received carboplatin/pemetrexed/bevacizumab. Median OS was 12.1 months (95% CI, 11.2–12.9 months) in the carboplatin/pemetrexed/bevacizumab group compared with 8.6 months (95% CI, 8.1–9.1 months) in the carboplatin/pemetrexed group (P<.001). Bevacizumab use remained associated with improved OS in a multivariate model (hazard ratio, 0.80; 95% CI, 0.75–0.86; P<.001). In the secondary, institutional analysis (N=539), the effect of bevacizumab was unchanged (hazard ratio, 0.75; 95% CI, 0.59–0.96; P=.02). Conclusions: In this large, real-world dataset, the addition of bevacizumab to first-line carboplatin/pemetrexed for metastatic nonsquamous NSCLC was associated with improved OS.

Submitted August 29, 2018; accepted for publication October 25, 2018.

Author contributions: Study concept and design: Bagley, Cohen, Langer. Data acquisition: Talento, Meropol. Data analysis and interpretation: Bagley, Mitra, Vachani. Manuscript preparation: Bagley. Critical revision: All authors.

Disclosures: Dr. Bagley has disclosed that he has received grant/research support from Eli Lilly. Dr. Meropol has disclosed that he is an employee of and has stock options in Flatiron Health, Inc., an independent subsidiary of the Roche Group. Dr. Langer has disclosed that he has received grant/research support from and served as a scientific advisor for Roche/Genentech and Eli Lilly. The remaining authors have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by a grant from the NCI (T32 CA009679) and the National Institute of Environmental Health Sciences (P30-ES013508).

Correspondence: Stephen J. Bagley, MD, MSCE, Division of Hematology/Oncology, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104. Email: stephen.bagley@uphs.upenn.edu
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