Impact of prolonged and early bevacizumab treatment on the overall survival of EGFR-mutant and EGFR-wild type nonsquamous non-small cell lung cancer

Background: VEGF plays a key role in tumor angiogenesis and immunosuppression. VEGF-blocking has proven beneficial for EGFR mutant and wild-type nonsquamous non-small cell lung cancer (nonsq-NSCLC); however, the number of cycles and treatment line yielding the optimal benefit are unknown. Methods: We retrospectively analyzed the data of 115 patients with advanced/metastatic nonsq-NSCLC administered at least one cycle of bevacizumab. The number of bevacizumab cycles was treated as a time-dependent covariate. Predictors of overall survival (OS) were investigated. Results: Bevacizumab was used as first-line treatment in 47 (40.9%) patients, with a median of five cycles (range: 1–31). Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.68–8.51; P < 0.001), wild-type EGFR (HR 2.61, 95% CI 1.45–4.70; P = 0.001), and bleeding during bevacizumab treatment (HR 3.63, 95% CI 1.77–7.45; P < 0.001) were predictive of poor OS; the number of bevacizumab cycles and first-line administration were not. In the wild-type EGFR subgroup, the number of bevacizumab cycles (≥ 5 vs. 1–4) was associated with a significant OS benefit (HR 0.28, 95% CI 0.08–0.98; P = 0.044); first-line administration also showed an OS benefit (HR 0.48, 95% CI 0.20–1.17; P = 0.105). A significant association between the number of cycles and EGFR status was identified (P = 0.046). Conclusion: OS benefit is negatively affected by bleeding events in bevacizumab-treated patients. Prolonged and early introduction of bevacizumab may provide an OS benefit for patients with wild-type EGFR nonsq-NSCLC.