JTO clinical and research reports · 2026
Clinical Activity of RET TKI Plus Chemotherapy After Progression on a RET TKI in a RET Fusion-Positive NSCLC Real-World Cohort: A Brief Report.
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Paula Alvaro Guimaraes, Liu Ximeng, Karimi Amirali, Concannon Kyle, Heeke Simon, Elamin Yasir Y, Wang Kaiwen, Pozadzides Jenny V, Vokes Natalie, Tu Janet, Tsao Anne, Negrao Marcelo V, Zhang Jianjun, Singhi Eric K, Zhang Bingman, Rinsurongkawong Waree, Martins Isadora Guimaraes, Tran Hai T, Gibbons Don L, Nilsson Monique B, Heymach John V
Аннотация
INTRODUCTION: RET fusion-driven NSCLC accounts for 2% of advanced lung adenocarcinomas, and selective RET tyrosine kinase inhibitors (RETis) are the current first-line standard-of-care treatment. However, acquired resistance to RETi can arise, and improved therapies for RETi-resistant tumors are needed.
METHODS: This real-world retrospective cohort evaluated the outcomes of the combinations of chemotherapy with RETi (chemo/RETi) and chemotherapy with immunotherapy (chemo/IO) in patients with NSCLC who experienced progression while receiving RETi. For both groups, we assessed the overall response rate, using the Response Evaluation Criteria in Solid Tumors version 1.1; estimated progression-free survival (PFS) and overall survival using the Kaplan-Meier method; described the genomic features potentially related to RETi resistance; and analyzed safety data using the Common Terminology Criteria for Adverse Events version 5.0.
RESULTS: Overall, 12 patients were included. The median PFS was 7.8 months for patients receiving chemo/RETi (n = 8) versus 3.5 months for patients receiving chemo/IO (n = 4); hazard ratio for progression or death was 0.24 (95% confidence interval: 0.07-0.83; p = 0.0063). The overall response rate was 38% in the chemo/RETi group and 25% in the chemo/IO group; one metabolic complete response was observed in the chemo/RETi group. Overall survival did not differ significantly between groups. Although chemo/RETi demonstrated improved outcomes, it was associated with more grade 3 treatment-related adverse events, including anemia, febrile neutropenia, and thrombocytopenia, compared with chemo/IO.
CONCLUSIONS: Our data support the potential efficacy of chemo/RETi after progression on RETi, with significantly better PFS than chemo/IO, albeit with higher rates of hematologic toxicities.
METHODS: This real-world retrospective cohort evaluated the outcomes of the combinations of chemotherapy with RETi (chemo/RETi) and chemotherapy with immunotherapy (chemo/IO) in patients with NSCLC who experienced progression while receiving RETi. For both groups, we assessed the overall response rate, using the Response Evaluation Criteria in Solid Tumors version 1.1; estimated progression-free survival (PFS) and overall survival using the Kaplan-Meier method; described the genomic features potentially related to RETi resistance; and analyzed safety data using the Common Terminology Criteria for Adverse Events version 5.0.
RESULTS: Overall, 12 patients were included. The median PFS was 7.8 months for patients receiving chemo/RETi (n = 8) versus 3.5 months for patients receiving chemo/IO (n = 4); hazard ratio for progression or death was 0.24 (95% confidence interval: 0.07-0.83; p = 0.0063). The overall response rate was 38% in the chemo/RETi group and 25% in the chemo/IO group; one metabolic complete response was observed in the chemo/RETi group. Overall survival did not differ significantly between groups. Although chemo/RETi demonstrated improved outcomes, it was associated with more grade 3 treatment-related adverse events, including anemia, febrile neutropenia, and thrombocytopenia, compared with chemo/IO.
CONCLUSIONS: Our data support the potential efficacy of chemo/RETi after progression on RETi, with significantly better PFS than chemo/IO, albeit with higher rates of hematologic toxicities.