Efficacy of immunotherapy in RET fusion-positive NSCLC: A meta-analysis

Abstract

Background: The Rearranged during Transfection (RET) gene represents a rare driver mutation in non-small cell lung cancer (NSCLC) occurring in only 1 %–2 % of cases, with implications in targeted carcinogenesis. Despite the significant efficacy demonstrated by immunotherapy in advanced NSCLC with wild-type driver genes, its validation in RET fusion-positive patients is yet to be established. Objectives: This meta-analysis aims to systematically evaluate the effectiveness of immunotherapy in patients with RET fusion-positive NSCLC. Data sources: and Methods: PubMed and Web of Science databases were systematically searched for relevant studies. Outcomes including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were extracted for further analysis. Results: Ten real-world evidence (RWE) studies involving 7145 patients were enrolled in this meta-analysis. In terms of tumor response, the pooled ORR and DCR were 24.0 % and 61.0 %, respectively. Regarding survival analysis, the pooled median PFS and median OS were 4.17 months [95 % confidence interval (CI): 3.40–5.02) and 17.22 months (95 % CI: 11.58–23.91)], respectively. Subgroup analyses showed that immunotherapies plus chemotherapy were superior to single-immunotherapy in terms of ORR, DCR, and median PFS, which were 43 % (95 % CI: 31%–55 %) vs. 17 % (95 % CI: 11%–25 %), 74 % (95 % CI: 60%–84 %) vs. 45 % (95 % CI: 31%–59 %) and 6.69 months (95 % CI: 4.91–8.93) vs. 2.96 months (95 % CI: 2.25–3.78), respectively. Conclusions: To date, RET fusions appear to be associated with poor response to immunotherapy in NSCLC patients, and immunotherapy combined with chemotherapy seems to offer greater clinical benefits than mono-immunotherapy.

Keywords

• RET fusion
• Non-small cell lung cancer
• Immunotherapy
• Meta-analysis