Clinical Activity of RET TKI Plus Chemotherapy After Progression on a RET TKI in a RET Fusion-Positive NSCLC…

Cohort studyJTO clinical and research reports· Aug 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.

Alvaro Guimaraes Paula, Ximeng Liu, Amirali Karimi … John V Heymach

HematologyCohort studyTreatmentQ1IF 3.3

Chemotherapy plus RET inhibitor was associated with a lower hazard of progression or death.

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.

Alvaro Guimaraes Paula … John V Heymach

JTO clinical and research reports · Aug 2026

Background

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.

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.

n = 12 patients

Results

chemo/RETi had a lower risk of cancer worsening or death

HR 0.24 (95% CI 0.07 to 0.83)

null 1

0.07

0.83

CI excludes the null - significant

More results

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.

More results

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.

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Conclusion

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.

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.

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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