Efficacy of immunotherapy in RET fusion-positive NSCLC: A meta-analysis
Zhongsheng Peng1, Kaibo Ding1, Mingying Xie2
1Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
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.
Insights
Immunotherapy shows limited effectiveness in non-small cell lung cancer (NSCLC) with Rearranged during Transfection (RET) fusions. Combination therapy with chemotherapy offers improved outcomes for these patients.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Rearranged during Transfection (RET) gene fusions are rare driver mutations in non-small cell lung cancer (NSCLC), found in 1-2% of cases.
- While immunotherapy is effective in advanced NSCLC with wild-type genes, its efficacy in RET fusion-positive NSCLC remains under investigation.
Purpose of the Study:
- To systematically evaluate the effectiveness of immunotherapy in patients with RET fusion-positive NSCLC.
- To compare the efficacy of single-agent immunotherapy versus combination therapy (immunotherapy plus chemotherapy).
Main Methods:
- A meta-analysis of real-world evidence (RWE) studies was conducted.
- PubMed and Web of Science databases were searched for relevant studies.
- Outcomes analyzed included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- Ten RWE studies with 7145 patients were included.
- Pooled objective response rate (ORR) was 24.0%, and disease control rate (DCR) was 61.0%.
- Pooled median progression-free survival (PFS) was 4.17 months, and median overall survival (OS) was 17.22 months.
- Immunotherapy plus chemotherapy demonstrated superior ORR (43% vs. 17%), DCR (74% vs. 45%), and median PFS (6.69 vs. 2.96 months) compared to single-agent immunotherapy.
Conclusions:
- RET fusions are associated with a poor response to immunotherapy in NSCLC patients.
- Combination therapy of immunotherapy plus chemotherapy appears to provide greater clinical benefits than monotherapy for RET fusion-positive NSCLC.
