1654P Updated ARROW data: Pralsetinib in patients (pts) with advanced or metastatic RET-altered thyroid cancer (TC)

Abstract

Oncogenic RET alterations are targetable markers in pts with TC. In the phase I/II ARROW trial (NCT03037385; data cutoff 12 Apr 2021; intention-to-treat [ITT] population), pralsetinib at 400 mg once daily (QD) induced overall response rates (ORR) of 51% in pts with RET-mutant medullary TC (RETm MTC) previously treated with cabozantinib and/or vandetanib (C/V), 72% in treatment-naïve pts with RETm MTC, and 86% in pts with previously treated RET fusion-positive TC (RET-fp TC). We report updated data with longer follow-up. Adult pts with advanced or metastatic RET-altered TC from ARROW who initiated pralsetinib at 400 mg QD were included. Phase II primary endpoints: ORR by blinded independent central review (RECIST v1.1); safety. Key secondary endpoints: duration of response (DoR); progression-free survival (PFS); overall survival (OS). Efficacy endpoints were assessed in the ITT population (enrolment cutoff 18 Feb 2021); safety was assessed in all pts with RET-altered TC who initiated pralsetinib at 400 mg QD. At data cutoff (18 Oct 2021), the ITT population included 145 pts with RETm MTC (prior C/V: n=67; other prior systemic therapy: n=11; treatment naïve: n=67), and 25 pts with previously treated RET-fp TC. Pts with RETm MTC previously treated with C/V had an ORR of 52% (35/67; 95% CI 39.7–64.6; 2 complete responses [CR]; 33 partial responses [PR]), a median DoR of 25.8 months (95% CI 18.0–not estimable [NE]) and a median PFS of 25.8 months (95% CI 19.7–35.0). Treatment-naïve pts with RETm MTC had an ORR of 72% (48/67; 95% CI 59.3–82.0; 4 CR; 44 PR); median DoR and median PFS were not reached (NR). Pts with previously treated RET-fp TC had an ORR of 84% (21/25; 95% CI 63.9–95.5; 4 CR; 17 PR); median DoR was 23.6 months (95% CI 15.1–NE) and median PFS 25.4 months (95% CI 17.0–NE). In these three cohorts, median OS was NR. In the safety population (N=175), 29 pts (17%) experienced serious treatment-related adverse events (TRAE). One (0.6%) TRAE-related death (pneumocystis jirovecii pneumonia) was reported. TRAEs led to discontinuation or dose reduction in 6% and 53% of pts, respectively. In this updated analysis (ITT population), pralsetinib continued to show efficacy and an acceptable safety profile in pts with RET-altered TC.