As reported in the Journal of Clinical Oncology by Alexander Drilon, MD, and colleagues, an updated analysis of the multicohort phase I/II LIBRETTO-001 trial confirmed the activity of selpercatinib in patients with RET fusion–positive advanced non–small cell lung cancer (NSCLC). The trial supported the May 2020 accelerated approval of selpercatinib in this setting, with the updated data set for objective response rate and response duration supporting the September 2022 conversion to regular approval.
Alexander Drilon, MD
Study Details
In the trial, patients with RET-altered cancers were enrolled from sites in 16 countries between May 2017 and May 2020 and received selpercatinib at 20 to 240 mg twice daily in phase I and at 160 mg twice daily in phase II. The NSCLC cohort consisted of 316 patients with RET fusion–positive disease; 247 had received prior platinum-based chemotherapy, and 69 were treatment-naive. The primary endpoint was objective response on independent review committee assessment.
Responses
Among 247 previously treated patients, an objective response was observed in 151 (61%, 95% confidence interval [CI] = 55%–67%), with complete response seen in 18 (7%). Median response duration was 28.6 months (95% CI = 20.4 months to not evaluable), with 49% of responses ongoing at data cutoff. Median progression-free survival was 24.9 months (95% CI = 19.3 months to not evaluable), with 1- and 2-year rates of 71% and 51%. Median overall survival was not reached, with an estimated 2-year rate of 69%.
Among 69 treatment-naive patients, an objective response was observed in 58 (84%, 95% CI = 73%–92%), with a complete response seen in 4 (6%). Median duration of response was 20.2 months (95% CI = 13.0 months to not evaluable), with 40% of responses ongoing at data cutoff. Median progression-free survival was 22.0 months (95% CI = 13.8 months to not evaluable), with 1- and 2-year rates of 71% and 42%. Median overall survival was not reached, with an estimated 2-year rate of 69%.
Among 26 patients with measurable baseline central nervous system (CNS) metastasis, an intracranial objective response was observed in 22 (85%, 95% CI = 65%–96%), with a complete response seen in 7 (27%). Median duration of CNS response was 9.4 months (95% CI = 7.4–15.3 months).
KEY POINTS
- Objective response was observed in 61% of patients who had received prior platinum-based chemotherapy.
- Objective response was observed in 84% of treatment-naive patients.
Adverse Events
In the total safety population of 796 patients who received selpercatinib for RET-altered cancers, grade ≥ 3 adverse events occurred in 79%, most commonly hypertension (20%), increased alanine aminotransferase (11%), increased aspartate aminotransferase (9%), diarrhea (5%), and QT prolongation (5%). Serious adverse events occurred in 44% of patients, most commonly pneumonia (4%). One fatal adverse event—acute respiratory failure—was considered related to treatment. According to the investigators, the safety profile in patients with NSCLC was similar to that in the total safety population.
The investigators concluded: “In a large cohort with extended follow-up, selpercatinib continued to demonstrate durable and robust responses, including intracranial activity, in previously treated and treatment-naive patients with RET fusion–positive NSCLC.”
Dr. Drilon, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Loxo Oncology, a wholly owned subsidiary of Eli Lilly and Company. For full disclosures of the study authors, visit ascopubs.org.
