Selpercatinib Treatment Beyond Progression in <i>RET</i> Fusion–Positive Non–Small Cell Lung Cancer

PURPOSE Selpercatinib, a highly selective RET kinase inhibitor with CNS activity, is approved in multiple countries for patients with RET fusion–positive non–small cell lung cancer (NSCLC). METHODS Patients with NSCLC were treated on the phase I/II LIBRETTO-001 trial (ClinicalTrials.gov identifier: NCT03157128 ) and were permitted to continue selpercatinib beyond investigator-assessed progressive disease (PD) if the patient derived ongoing benefit according to the investigator and with sponsor approval. Data from patients with PD confirmed by an independent review committee were used for this analysis (N = 80 of 356 patients with NSCLC enrolled; data cutoff date of January 13, 2023). RESULTS Eighty patients had radiologically confirmed PD and continued selpercatinib per investigator assessment. Median duration of treatment beyond PD was 5.9 months. Of the 80 patients, 57 had oligoprogression (oligoPD), including 20 with 1-2 progressing lesions and 37 with 3-5 progressing lesions, whereas 23 had widespread progression (more than five progressing lesions). Median time on treatment beyond PD for patients with oligoPD was 9.8 months. Postprogression median time on treatment (ToT) appeared comparable between patients who progressed in CNS only (n = 8; 7.5 months) versus patients with extracranial PD (n = 68; 6.4 months). Of the 80 patients receiving postprogression therapy, 33 (41.3%) received local radiotherapy upon disease progression. Concurrent radiotherapy extended the ToT for patients across all subpopulations. CONCLUSION Continuing selpercatinib beyond progression is feasible and may be considered, particularly for patients with limited oligoPD, including patients with CNS progression.