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

J Natl Compr Canc Netw. 2019 May 1;17(5):469-477. doi: 10.6004/jnccn.2018.7102.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Drug Administration Schedule
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Pemetrexed / administration & dosage
  • Prognosis
  • Proportional Hazards Models
  • Treatment Outcome

Substances

  • Pemetrexed
  • Bevacizumab
  • Carboplatin