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Accelerated FDA approval for pralsetinib in RET-fusion positive NSCLC

The ph 1/2 ARROW study includes several pivotal tumor cohorts, including RET-fusion positive NSCLC (prior platinum-based CT or treatment-naïve) and RET-fusion or RET-mutated thyroid cancer.

RET-fusions can be found in approximately 2% of NSCLC, and 10-20% of RAI-refractory thyroid cancer. RET mutations are present in >90% of medullary thyroid cancer.

Approval of pralsetinib comes just months after approval of Loxo/Lilly’s RET inhibitor selpercatinib for RET-fusion positive NSCLC. Both agents were approved on ORR by BIRC for the ITT population. In pts with prior platinum-based therapy, ORR was 55% for pralsetinib and 64% for selpercatinib. In treatment-naïve pts, ORR was 66% and 85%, respectively.

Does the higher response rate in tx-naïve pts bode well for selpercatinib? We’ll have to wait to see mDOR and mPFS. It is interesting to speculate, though, as both agents have an ongoing phase 3 study comparing single agent to platinum-based CT.

Selpercatinib was also approved for RET-fusion positive thyroid cancer and RET-mutated medullary thyroid cancer. Blueprint/Roche will have to wait until early next year to add these indications to its label.


ARROW: NCT03037385
Gainor et al., ASCO 2020: 9515
Drilon et al., NEJM. 2020 (PMID: 32846060)