First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC

Zhou, C; Solomon, B; Loong, HH; Park, K; Perol, M; Arriola, E; Novello, S; Han, B; Zhou, J; Ardizzoni, A; Mak, MP; Santini, FC; Elamin, YY; Drilon, A; Wolf, J; Payakachat, N; Uh, MK; Rajakumar, D; Han, H; Puri, T; Soldatenkova, V; Lin, AB; Lin, BK; Goto, K; LIBRETTO-431 Trial Investigators

Author(s): Zhou, C; Solomon, B; Loong, HH; Park, K; Perol, M; Arriola, E; Novello, S; Han, B; Zhou, J; Ardizzoni, A; Mak, MP; Santini, FC; Elamin, YY; Drilon, A; Wolf, J; Payakachat, N; Uh, MK; Rajakumar, D; Han, H; Puri, T; Soldatenkova, V; Lin, AB; Lin, BK; Goto, K; LIBRETTO-431 Trial Investigators;
Details: Publication Year 2023-11-16,Volume 389,Issue #20,Page 1839-1850
Journal Title: New England Journal of Medicine
Publication Type: Research article
Abstract: BACKGROUND: Selpercatinib, a highly selective potent and brain-penetrant RET inhibitor, was shown to have efficacy in patients with advanced RET fusion-positive non-small-cell lung cancer (NSCLC) in a nonrandomized phase 1-2 study. METHODS: In a randomized phase 3 trial, we evaluated the efficacy and safety of first-line selpercatinib as compared with control treatment that consisted of platinum-based chemotherapy with or without pembrolizumab at the investigator's discretion. The primary end point was progression-free survival assessed by blinded independent central review in both the intention-to-treat-pembrolizumab population (i.e., patients whose physicians had planned to treat them with pembrolizumab in the event that they were assigned to the control group) and the overall intention-to-treat population. Crossover from the control group to the selpercatinib group was allowed if disease progression as assessed by blinded independent central review occurred during receipt of control treatment. RESULTS: In total, 212 patients underwent randomization in the intention-to-treat-pembrolizumab population. At the time of the preplanned interim efficacy analysis, median progression-free survival was 24.8 months (95% confidence interval [CI], 16.9 to not estimable) with selpercatinib and 11.2 months (95% CI, 8.8 to 16.8) with control treatment (hazard ratio for progression or death, 0.46; 95% CI, 0.31 to 0.70; P<0.001). The percentage of patients with an objective response was 84% (95% CI, 76 to 90) with selpercatinib and 65% (95% CI, 54 to 75) with control treatment. The cause-specific hazard ratio for the time to progression affecting the central nervous system was 0.28 (95% CI, 0.12 to 0.68). Efficacy results in the overall intention-to-treat population (261 patients) were similar to those in the intention-to-treat-pembrolizumab population. The adverse events that occurred with selpercatinib and control treatment were consistent with those previously reported. CONCLUSIONS: Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive NSCLC. (Funded by Eli Lilly and others; ClinicalTrials.gov number, NCT04194944.).
Department(s): Medical Oncology
PubMed ID: 37870973
Publisher's Version: https://doi.org/10.1056/NEJMoa2309457
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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