Larotrectinib Subgroup Analyses Demonstrate Long-Term Efficacy, Safety Profile in NTRK Gene Fusion Cancer

New data from 3 post-hoc subgroup analyses with larotrectinib (Vitrakvi; Bayer) highlight its long-term efficacy and safety profile in both adult and pediatric patients with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation, are metastatic, or where surgical resection is likely to result in severe morbidity, and who have no satisfactory alternative treatments or have progressed following treatment.

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The new findings were presented at the American Society of Clinical Oncology (ASCO) 2023 meeting. This indication was approved by the FDA under accelerated approval, based on overall response rate (ORR) data and duration of response (DoR) in clinical trials. Continued approval may be contingent upon confirmatory trial findings.

In the first post-hoc subgroup analysis presented at ASCO of adult patients with tropomyosin receptor kinase (TRK) fusion cancer across 24 different tumor types, including those with central nervous system (CNS) metastases, treatment with larotrectinib demonstrated an ORR of 57%, including 16% complete responses and 41% partial responses. In evaluable patients with CNS metastases, ORR was 68%.

Among all patients, the median time to response was 1.8 months and median DoR was 43.3 months at a median follow-up of 32.3 months. Treatment-related adverse events (AEs) were predominantly grade 1 or 2, with grade 3 or 4 AEs occurring in 14% of patients.

In the second analysis, investigators examined long-term efficacy and safety of larotrectinib in patients with TRK fusion lung cancer. In an expanded dataset with longer follow-up, the treatment demonstrated long-term efficacy and safety data in adult patients, including those with CNS metastases. The results emphasize the importance of wider adoption of next-generation sequencing testing for identifying patients with solid tumors harboring NTRK gene fusions, including lung cancer.

Among 27 adult patients with TRK fusion lung cancer eligible for assessment, ORR was 74%, including 11% complete responses and 63% partial responses. Among the 12 patients with baseline CNS metastases, the ORR was 67%, with 8 partial responses.

Median DoR was 33.9 months and median follow-up was 22.9 months. Finally, treatment-related AEs were predominantly grade 1 or 2; grade 3 or 4 treatment-related AEs were reported in 5 patients and included aspartate aminotransferase increase, alanine transaminase increase, myalgia, and hypersensitivity.

In the final analysis, larotrectinib was evaluated in updated subgroup analyses of patients with TRK fusion thyroid cancer. Among those eligible for efficacy assessment, 47% had NTRK1 and 53% had NTRK2. Fifty percent of patients received no prior systemic therapies, 20% received 2 or more, and 77% received prior radioiodone.

ORR was 63%, including 10% complete responses and 53% partial responses. For participants classified as differentiated thyroid cancer, ORR was 78%.

For those classified as differentiated thyroid cancer, ORR was 78%, and for those classified as anaplastic thyroid cancer, ORR was 14%. All patients with CNS metastases at baseline had a partial response. The median time to response was 1.9 months and median DoR was 43.3 months at a median follow-up of 32.3 months.

For grade 3 or higher treatment-related AEs, anemia and decreased lymphocyte count were reported in 7% of patients. There were no treatment discontinuations due to treatment-related AEs.

Taken together, investigators said all of these analyses demonstrate the long-term efficacy and safety profile of larotrectinib in those with NTRK gene fusion cancer, across solid tumor types.

“These findings reinforce Vitrakvi’s ability to treat patients with NTRK fusion-positive cancer and the importance of targeting the oncogenic driver,” said Iain Webb, MD, vice president of US Medical Affairs, Oncology at Bayer, in a press release. “Testing patients comprehensively and early is pivotal to finding patients with NTRK fusion tumors and treating appropriate patients with Vitrakvi.”

REFERENCE

Latest Vitrakvi (Larotrectinib) Subgroup Analyses at ASCO 2023 Showcase Long-Term Efficacy and Safety Profile in Adult and Pediatric Patients with NTRK Gene Fusion Cancer, Across Solid Tumors. News release. Bayer. June 2, 2023. Accessed June 2, 2023. https://www.businesswire.com/news/home/20230601006134/en/Latest-Vitrakvi%C2%AE-larotrectinib-Subgroup-Analyses-at-ASCO-2023-Showcase-Long-Term-Efficacy-and-Safety-Profile-in-Adult-and-Pediatric-Patients-with-NTRK-Gene-Fusion-Cancer-Across-Solid-Tumors