Durvalumab and tremelimumab combination therapy versus durvalumab monotherapy in metastatic lung cancer: A systematic review and meta-analysis.

Abstract

e20518 Background: Metastatic lung cancer (mLC) is a leading cause of cancer-related mortality, with limited benefits from standard chemotherapy. Immune checkpoint inhibitors enhance anti-tumor immunity, such as durvalumab (PD-L1 inhibitor) and tremelimumab (CTLA-4 inhibitor). This systematic review and meta-analysis evaluated the efficacy and safety of durvalumab + tremelimumab therapy versus durvalumab alone in improving survival outcomes and treatment response in mLC. Methods: A comprehensive search of PubMed, Embase, and Scopus was conducted from inception until January 2025. The primary outcomes analyzed included overall survival (OS) at 12 months, progression-free survival (PFS) at 12 months, and objective response rate (ORR). Adverse events were categorized into hematological and non-hematological events. Hematological adverse events included any grade of anemia, neutropenia, and thrombocytopenia. Non-hematological adverse events included any grade of diarrhea and vomiting. Data were analysed using a random-effects model in RevMan (version 5.4.1) to account for variability across studies and provide pooled estimates. Results: This meta-analysis of four randomised controlled trials (RCTs) involving 1,829 patients compared durvalumab + tremelimumab (n = 943) with durvalumab mono therapy (n = 886). OS at 12 months showed a significant difference favouring the durvalumab group (RR: 0.81, 95% CI: 0.67–0.97, p = 0.03). No statistical difference was observed for PFS at 12 months (RR: 0.98, 95% CI: 0.92–1.04, p = 0.51) or ORR (RR: 1.02, 95% CI: 0.88–1.19, p = 0.77). Anaemia (RR: 1.19, 95% CI: 0.99–1.42, p = 0.06), thrombocytopenia (RR: 1.43, 95% CI: 0.93–2.18, p = 0.10), and vomiting (RR: 1.22, 95% CI: 0.56–2.63, p = 0.62) showed no statistical difference between the groups. Neutropenia (RR: 1.33, 95% CI: 1.03–1.72, p = 0.03) and diarrhea (RR: 1.45, 95% CI: 1.11–1.91, p = 0.007) were significantly more frequent in the durvalumab + tremelimumab group, favouring the durvalumab group for neutropenia. Conclusions: This meta-analysis demonstrates that durvalumab provides superior overall survival at 12 months compared to durvalumab + tremelimumab, with no significant differences observed for progression-free survival or objective response rate. While anaemia, thrombocytopenia, and vomiting showed no significant differences, neutropenia and diarrhea were significantly more frequent with the addition of tremelimumab. These findings highlight the need for careful patient selection and toxicity management when considering the addition of tremelimumab to treatment regimens and call for further research to refine its role in mLC therapy.