Updated Biomarker Analysis (BRAF and RAS Mutations) From the Phase 3 SELECT Study of Lenvatinib (LEN) in Radioiodine-Refractory Differentiated Thyroid Cancer (RR-DTC)

  • Background: LEN is an oral multikinase inhibitor of VEGFR1-3, FGFR1-4, PDGFR?, RET, and KIT. In the Ph3 SELECT trial of LEN versus placebo in patients with RR-DTC, LEN significantly prolonged median progression-free survival (mPFS).1 This exploratory post hoc biomarker analysis of SELECT investigated whether genomic mutations in BRAF and/or RAS were associated with improved efficacy outcomes in LEN-treated patients.

    Methods: Archival tumor tissues were collected (if available) from 183/392 patients enrolled in SELECT (LEN, n=123/261; placebo n=60/131). Tissues were subsequently analyzed for BRAF (V600E) and NRAS/KRAS/HRAS (RAS) mutation and efficacy outcomes determined for LEN-treated patients.  

    Results: LEN-treated patients with a BRAF mutation (n=26/123; 21%) compared with wildtype BRAF (n=97/123; 79%) had longer mPFS (36.8 vs 16.6 months, HR=0.67, 95%CI: 0.37-1.20), median overall survival (mOS: 56.4 vs 39.6 months, HR=0.69, 95%CI: 0.37-1.28) and median duration of response (mDOR: 35.2 vs 25.8 months). The overall response rate (ORR) for patients with BRAF-mutations vs wildtype was 53.8% vs 67.0%. Patients with RAS mutation (n=34/122; 28%) compared with wildtype (n=88/122; 72%) had mPFS of 17.2 vs 24.3 months (HR=0.75, 95%CI: 0.44-1.30), mOS of 44.3 vs 39.6 months (HR=0.82, 95%CI: 0.48-1.41), mDOR of 30.0 vs 30.5 months, and ORR of 70.6% vs 61.4%. Three patients had both BRAF and RAS mutations.

    Conclusions: In this exploratory post hoc biomarker analysis from SELECT, LEN-treated patients with BRAF or RAS mutations had nominally longer mOS compared with those with wildtype BRAF or RAS. Further research is warranted in patients with RR-DTC and BRAF or RAS mutation.


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