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BACKGROUND Single agent immune checkpoint inhibitors (ICIs) improve survival outcomes compared to chemotherapy for advanced non-small cell lung cancer (NSCLC), but treatment efficacy widely varies. The combination of ICIs with chemotherapy has shown promising efficacy over chemotherapy alone; however, whether this strategy is superior to single agent ICIs for the treatment of advanced NSCLC remains unknown. METHODS The records of 109 patients with advanced NSCLC who were administered at least one cycle of ICIs were retrospectively reviewed. Patients were grouped based on the presence or absence of a chemotherapy treatment combination. Efficacy and survival outcomes were analyzed. RESULT Sixty-nine (58.0%) patients received single agent ICIs (ICI group) and 50 (42.0%) received ICIs and chemotherapy (ICC group). The median (3.2 vs. 3.0 months; P = 0.025) and one-year (34.5 vs. 9.6%; P = 0.026) progression-free survival (PFS) rates were significantly better in the ICC than in the ICI group. The superior efficacy of ICC remained in the propensity score matched pairs (median PFS 3.2 vs. 2.6 months, P = 0.032; 1-year PFS 35.2 vs. 7.6%; P = 0.035). Eastern Cooperative Oncology Group performance status 0-1 (HR 0.37, 95% CI 0.22-0.62; P < 0.001) and the ICC group (HR 0.56, 95% CI 0.34-0.94; P = 0.028) were predictive of PFS. Subgroup-to-chemotherapy interaction revealed improved risk reduction for adenocarcinoma and EGFR mutation. CONCLUSION Combing chemotherapy with ICIs improved treatment efficacy over ICIs alone. The additional efficacy of chemotherapy may differ between histological subtypes and EGFR mutation status.

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.