Efficacy and safety of pralsetinib in patients with advanced RET fusion‐positive non–small cell lung cancer

Abstract

AbstractBackgroundPralsetinib is a potent, selective RET inhibitor targeting oncogenic RET alterations. As part of the global, phase 1/2 ARROW trial (NCT03037385), the efficacy and safety of pralsetinib in Chinese patients with advanced RET fusion‐positive non–small cell lung cancer (NSCLC) were evaluated.MethodsAdult patients with advanced, RET fusion–positive NSCLC with or without prior platinum‐based chemotherapy were enrolled into two cohorts receiving 400‐mg once‐daily oral pralsetinib. Primary end points were objective response rates assessed by blinded independent central review and safety.ResultsOf 68 patients enrolled, 37 had received prior platinum‐based chemotherapy (48.6% with ≥3 prior systemic regimens) and 31 were treatment‐naïve. As of March 4, 2022 (data cutoff), of the patients with measurable lesions at baseline, a confirmed objective response was observed in 22 (66.7%; 95% confidence interval [CI], 48.2–82.0) of 33 pretreated patients, including 1 (3.0%) complete response and 21 (63.6%) partial responses; and in 25 (83.3%; 95% CI, 65.3–94.4) of 30 treatment‐naïve patients, including two (6.7%) complete responses and 23 (76.7%) partial responses. Median progression‐free survival was 11.7 months (95% CI, 8.7–not estimable) in pretreated patients and 12.7 months (95% CI, 8.9–not estimable) in treatment‐naïve patients. The most common grade 3/4 treatment‐related adverse events in 68 patients were anemia (35.3%) and decreased neutrophil count (33.8%). Eight (11.8%) patients discontinued pralsetinib because of treatment‐related adverse events.ConclusionPralsetinib showed robust and durable clinical activity with a well‐tolerated safety profile in Chinese patients with RET fusion‐positive NSCLC.Clinical trial registration: NCT03037385.