Document Type

Conference Proceeding

Publication Date


Publication Title

Ann Oncol


Background: The ARROW study is assessing the anti-tumour activity of pralsetinib, a highly-selective RET inhibitor in advanced solid tumours, including RET fusion+ NSCLC. Prolonged overall survival (OS) was reported with RET inhibitor therapy in NSCLC pts with CCDC6 vs KIF5B RET fusions (Tan AC, et al. JTO 2020). We examined the relationship between RET fusion partner and treatment outcomes in pts with RET fusion+ NSCLC from ARROW and RWD.

Methods: In phase 2 of ARROW, 233 pts with RET fusion+ NSCLC (KIF5B n=164, CCDC6 n=41, Other n=28) received 400mg/day pralsetinib until progression, intolerance or withdrawal. Primary endpoints: overall response rate (ORR) and safety. In Q4 2021, 67 pts with RET fusion+ NSCLC (KIF5B n=46, CCDC6 n=8, Other n=13) met eligibility criteria from the nationwide (US-based) de-identified Flatiron Health-FMI NSCLC clinico-genomic database. Cox regression analyses are reported.

Results: Baseline characteristics by RET fusion partner were balanced across subgroups within ARROW. ORR was similar with KIF5B and CCDC6, but lower with Other RET fusions (Table); the same trend was seen in treatment-naïve and prior treatment subgroups. Disease control rate (DCR) was high in all pts, but lowest in the Other RET fusions subgroup. Median duration of response (DOR) and progression-free survival (PFS) were higher with CCDC6 vs KIF5B RET fusions irrespective of prior treatment. OS data are immature. In the RWD cohort, median OS was numerically longer in CCDC6 and Other RET fusions vs KIF5B RET-driven disease (52.8 and 38.5 vs 19.1 months); when adjusted for covariates including RET inhibitor usage (KIF5B n=12, CCDC6 n=5, Other n=5), OS HRs for CCDC6 and Other RET fusions vs KIF5B were 0.49 (95% CI: 0.08–3.11) and 0.41 (95% CI: 0.13–1.30), respectively.

Conclusions: Pralsetinib is active in RET fusion+ NSCLC, regardless of fusion partner or prior treatment. CCDC6 RET-driven disease may have a better prognosis vs KIF5B.


Clinical trial identification: NCT03037385.



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