Overall Survival and Safety With Pemetrexed/Platinum ± Anti-VEGF Followed by Pemetrexed ± Anti-VEGF Maintenance in Advanced Nonsquamous Non–Small-Cell Lung Cancer: A Pooled Analysis of 4 Randomized Studies

Background: Before immune checkpoint blockade therapy, chemotherapy with pemetrexed maintenance was the standard of care for patients with advanced nonsquamous non-small-cell lung cancer (NSQ-NSCLC) and remains such where immunotherapy is not applicable. This pooled analysis aimed to characterize overall survival (OS) and safety of pemetrexed +/- anti-VEGF maintenance, by treatment duration. Patients and Methods: Data from four randomized clinical trials (PARAMOUNT, PRONOUNCE, PointBreak, JVBL) of patients with NSQ-NSCLC receiving pemetrexed +/- anti-VEGF maintenance therapy were pooled as two groups (Group A: pemetrexed-only maintenance, n=486; and Group B: pemetrexed + anti-VEGF maintenance, n=329). OS and treatment-emergent adverse events (TEAEs) were analyzed in both groups by treatment duration. Results: Baseline characteristics were well balanced between both groups. Median OS did not significantly differ between Group A (16.1 months) and Group B (18.4 months; hazard ratio: 1.17, p-value=0.1417). A correlation between median OS and treatment duration was numerically stronger in Group A (r=0.72) versus B (r=0.62). Across treatment groups, TEAEs were largely grade 1-2 and, with few exceptions, did not increase with increased treatment duration. Conclusion: There was no significant OS difference between pemetrexed-only and pemetrexed ± anti-VEGF maintenance in patients with NSQ-NSCLC. Patients receiving pemetrexed + anti-VEGF experienced a slightly less favorable safety profile with more reported TEAEs compared to pemetrexed monotherapy. Pemetrexed +/- anti-VEGF maintenance therapy may be considered in NSQ-NSCLC, based on an individualized patient approach, particularly where immunotherapy is not clinically indicated.