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Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancer: Final Safety and Efficacy, Including Overall
Oliver Gautschi1, Keunchil Park2,3, Benjamin J Solomon4
1University of Berne and Medical Oncology, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
Abstract:
LIBRETTO-001 (ClinicalTrials.gov identifier: NCT03157128) is a registrational phase I/II, single-arm, open-label trial of selpercatinib in RET-dependent cancers. With 19 months of additional follow-up, we report the final efficacy and safety results of selpercatinib in patients with RET fusion-positive non-small cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy (N = 247) or were treatment-naïve (N = 69). The objective response rate (ORR) was 62% for pretreated patients and 83% for treatment-naïve patients. Duration of response (DoR) was 31.6 months for pretreated and 20.3 months for treatment-naïve patients (median follow-up approximately 38 months). Median progression-free survival (PFS) was 26.2 months for pretreated and 22.0 months for treatment-naïve patients (median follow-up approximately 40 months). Median overall survival was 47.6 months in pretreated patients and was not reached in the treatment-naïve group (median follow-up approximately 43 months). At the 3-year landmark estimate, 57% of pretreated and 66% of treatment-naïve patients were alive. Among 26 patients with measurable CNS metastases at baseline, the CNS-ORR was 85% with a CNS-DoR of 9.4 months and CNS-PFS of 11.0 months. The safety profile of selpercatinib was consistent with previous reports. With substantial additional follow-up, selpercatinib continued to show durable responses and intracranial activity, with a manageable safety profile in patients with RET fusion-positive NSCLC.
Insights
Selpercatinib demonstrated durable efficacy in RET fusion-positive non-small cell lung cancer (NSCLC). The drug showed high response rates and long-term survival in both pretreated and treatment-naïve patients, including those with brain metastases.
Area of Science:
- Oncology
- Clinical Pharmacology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) driven by RET fusions represents a distinct molecular subtype.
- Targeted therapies are crucial for improving outcomes in these patients.
- Selpercatinib is a potent and selective RET inhibitor.
Purpose of the Study:
- To report final efficacy and safety results of selpercatinib in RET fusion-positive NSCLC.
- To evaluate selpercatinib in both previously treated and treatment-naïve patient populations.
- To assess the drug's activity in patients with central nervous system (CNS) metastases.
Main Methods:
- LIBRETTO-001 trial: a phase I/II, single-arm, open-label study.
- Patients with RET fusion-positive NSCLC received selpercatinib.
- Efficacy endpoints included objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- High ORR observed: 62% in pretreated and 83% in treatment-naïve patients.
- Durable responses: Median DoR of 31.6 months (pretreated) and 20.3 months (treatment-naïve).
- Long-term survival: Median OS of 47.6 months (pretreated), not reached (treatment-naïve); 3-year survival rates of 57% and 66%, respectively.
- Significant CNS activity: CNS-ORR of 85% in patients with baseline CNS metastases.
Conclusions:
- Selpercatinib provides substantial and durable clinical benefit in RET fusion-positive NSCLC.
- The drug demonstrates significant intracranial activity, addressing a critical unmet need.
- The safety profile remains consistent and manageable, supporting its role in treating this patient population.
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