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

• Published in: Clinical lung cancer 2022-05, Vol.23 (3), p.253-263
• Main Authors: Garon, Edward B., Peterson, Patrick, Rizzo, Maria Teresa, Kim, Jong Seok
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung; Clinical trial outcomes; Humans; Lung Neoplasms; Maintenance therapy; NSCLC; Pemetrexed; Platinum - therapeutic use; Safety; Survival
• ISSN: 1525-7304; 1938-0690
• DOI: 10.1016/j.cllc.2021.10.010

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. Data from 4 randomized clinical trials (PARAMOUNT, PRONOUNCE, PointBreak, JVBL) of patients with NSQ-NSCLC receiving pemetrexed ± anti-VEGF maintenance therapy were pooled as 2 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. 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= .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 to 2 and, with few exceptions, did not increase with increased treatment duration. 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. Data from 4 randomized studies of treatment with pemetrexed/platinum ± anti-VEGF followed by pemetrexed ± anti-VEGF maintenance for advanced nonsquamous non–small-cell lung cancer were pooled and analyzed for overall survival and safety. No significant difference in overall survival was found between pemetrexed-only versus pemetrexed + anti-VEGF maintenance. Both maintenance therapies were tolerable across the length of treatment.