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: Immunotherapy; Meta-analysis; Non-small cell lung cancer; RET fusion.

Fig. 1

Flow chart of articles identified, included and excluded.

Fig. 2

Forest plot of objective response rate (ORR) for all pooled studies. The Forest plot shows the pooled overall ORR for all studies, with an estimated ORR of 24 % (95 % CI: 14%–38 %, p = 0.05, I² = 45 %).

Fig. 3

A:Forest plot of objective response rate (ORR) for studies with immunochemotherapy. This forest plot displays the ORR for studies involving immunochemotherapy, with an estimated ORR of 43 % (95 % CI: 31%–55 %, p = 0.17, I² = 37 %). B: Forest plot of ORR for studies with mono-immunotherapy. This forest plot displays the ORR for studies involving mono-immunotherapy, with an estimated ORR of 17 % (95 % CI: 11%–26 %, p = 0.62, I² = 0 %).

Fig. 4

Forest plot of disease control rate (DCR) for all pooled studies. The forest plot illustrates the overall DCR across all studies, estimating a DCR of 61 % (95 % CI: 46%–74 %, p = 0.08, I² = 45 %).

Fig. 5

A: Forest plot of disease control rate (DCR) for studies with immunochemotherapy. This forest plot depicts the DCR for studies with immunochemotherapy, demonstrating a DCR of 74 % (95 % CI: 60%–84 %, p = 0.65, I² = 0 %). B: Forest plot of DCR for studies with mono-immunotherapy. This forest plot depicts the DCR for mono-immunotherapy studies, with an estimated DCR of 45 % (95 % CI: 31%–59 % p = 0.24, I² = 29 %).