Alexander Drilon, MD
As reported in the Journal of Clinical Oncology by Alexander Drilon, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, and colleagues, final results of the registrational phase I/II LIBRETTO-001 trial showed continued benefit of the RET receptor tyrosine kinase inhibitor selpercatinib in patients with RET gene fusion–positive non–small cell lung cancer (NSCLC).1
Study Details and Key Findings
The primary analysis led to the U.S. Food and Drug Administration approval of selpercatinib in patients with RET gene fusion–positive locally advanced or metastatic NSCLC in 2022. With an additional 19 months of follow-up, the investigators reported final efficacy results from those who had previously received platinum-based chemotherapy (n = 247) or were treatment-naive (n = 69). The final safety analysis included all patients who received at least one dose of selpercatinib (n = 362).
Selpercatinib was administered in 28-day continuous cycles of 20 mg once daily to 240 mg twice daily during dose escalation. The recommended phase II dose was 160 mg twice daily. Treatment was administered until disease progression, death, withdrawal of consent, or unacceptable toxicity.
The objective response rates were 62% for pretreated patients and 83% for treatment-naive patients, with median response durations of 31.6 and 20.3 months, respectively. Median progression-free survival times were 26.2 months for pretreated patients and 22.0 months for treatment-naive patients. Median overall survival was 47.6 months for pretreated patients and not reached for treatment-naive patients. On a 3-year landmark estimate, 57% of pretreated and 66% of treatment-naive patients were alive.
Among 26 patients with measurable central nervous system (CNS) metastases at baseline, the CNS objective response rate was 85%, with a median CNS response duration of 9.4 months and a median CNS progression-free survival of 11.0 months.
The safety profile of selpercatinib was found to be consistent with previous reports.
The investigators concluded: “With substantial additional follow-up, selpercatinib continued to show durable responses and intracranial activity with a manageable safety profile in patients with RET [gene] fusion–positive NSCLC.”
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.
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