Selpercatinib vs Chemotherapy for RET Fusion–Positive NSCLC: Phase III Findings

By: Joshua Swore, PhD
Posted: Thursday, February 1, 2024

Findings from a phase III study of patients with non–small cell lung cancer (NSCLC) treated with selpercatinib have been published in The New England Journal of Medicine. The RET kinase inhibitor with central nervous system (CNS) penetration yielded “significantly longer” progression-free survival than platinum-based chemotherapy (with or without pembrolizumab) in patients who had advanced NSCLC and RET fusion, according to Koichi Goto, MD, PhD, of the National Cancer Center Hospital East, Kashiwa, Japan, and colleagues.

“Selpercatinib...has previously been shown to have marked efficacy in nonrandomized studies involving patients with RET-driven lung, thyroid, and other solid tumors,” the investigators noted.

The study included 212 patients who were randomly assigned with a final ratio of 1.6:1 to receive either selpercatinib or cisplatin as treatment combined with an investigator’s choice of platinum-based chemotherapy with or without pembrolizumab. The interim efficacy analysis was determined to be the occurrence of 98 events of disease progression.

At the time of interim efficacy analysis, the group reported a median progression-free survival of 24.8 months with selpercatinib and 11.2 months without it (hazard ratio for disease progression or death = 0.46; 95% confidence interval = 0.31–0.70; P < .001). An objective response was found among 84% of patients treated with selpercatinib and 65% of patients treated with the control agent.

The authors reported adverse effects for patients treated with selpercatinib to include hypertension, diarrhea, edema, and increased bilirubin. Patients treated with the control agent had a greater incidence of anemia, fatigue, neutropenia, nausea, and constipation. Incidents of grade 3 events were higher among patients treated with selpercatinib (70% vs 57%), leading 51% of patients to initiate a dose reduction.

Disclosure: For full disclosures of the study authors, visit www.nejm.org.

The New England Journal of Medicine