WCLC 2025 - Posters & ePosters-P3.12.06 Pralsetinib (Phase 1/2 ARROW Trial) Compared With Best Available Therapy (External Control) in Pretreated RET Fusion+ NSCLC

P3.12.06 Pralsetinib (Phase 1/2 ARROW Trial) Compared With Best Available Therapy (External Control) in Pretreated RET Fusion+ NSCLC

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This study compares the outcomes of pralsetinib, a selective RET inhibitor, to best available therapy (BAT) in patients with previously treated, advanced RET fusion-positive non-small cell lung cancer (NSCLC), using data from the Phase 1/2 ARROW trial and a real-world (RW) external control cohort. RET fusions occur in about 2% of NSCLC cases, often in younger patients, and pralsetinib was FDA-approved in 2020 for metastatic RET fusion-positive NSCLC.<br /><br />The RW cohort included 22 patients (27 lines of therapy) treated after RET fusion identification with standard therapies including tyrosine kinase inhibitors (e.g., cabozantinib, vandetanib) and chemotherapy. Patients were required to have metastatic or locally advanced RET+ NSCLC, documented performance status, and to have started treatment at least three months before data collection or until death.<br /><br />Baseline characteristics were generally comparable but with some differences: RW patients had a higher proportion with ECOG 0 status (55.6% vs 30.8%), a slightly higher rate of Stage IV disease, fewer CNS metastases, and varied prior therapy exposure. Adjustments were made for these differences in analysis.<br /><br />Key results showed that the objective response rate (ORR) was significantly higher with pralsetinib (61.4%) than BAT (25.9%). Median progression-free survival (PFS) was 16.8 months for pralsetinib versus 3.5 months for BAT. Median overall survival (OS) was not reached in the pralsetinib group but was 9.1 months in the RW cohort, with 12-month survival rates of 74.6% versus 58.4%. Adjusted hazard ratios favored pralsetinib with significant reductions in risk of progression (HR 0.13, p<0.001) and death (HR 0.28, p<0.001).<br /><br />Limitations include small RW sample size, retrospective data collection, possible unmeasured confounding, and imaging variability. Despite these, the study applied rigorous methods to enhance comparability.<br /><br />In conclusion, pralsetinib demonstrated superior efficacy over BAT as second-line or later therapy in RET fusion-positive NSCLC, with higher response rates, and significantly improved progression-free and overall survival, supporting its use in this population following prior treatment.

Asset Subtitle

Domenico Galetta

Meta Tag

Speaker Domenico Galetta

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

pralsetinib

RET fusion-positive NSCLC

non-small cell lung cancer

ARROW trial

best available therapy

objective response rate

progression-free survival

overall survival

real-world cohort

tyrosine kinase inhibitors