Abstract 465P
Background
Larotrectinib (L), a highly selective Neurotrophic Tropomyosine Receptor Kinase (NTRK) inhibitor, was among the earliest drugs to receive histo-agnostic approvals from the FDA and EMA for treatment of locally advanced/metastatic (adv) NTRK-fusion-positive solid tumors progressing after standard-of-care therapies. These authorizations were granted after demonstration of efficacy in phase II clinical trials; rarity and heterogeneity of related tumors will make randomized trial difficult to consider. In France, L could be prescribed within specific Expanded Access Program (EAP) in patients (pts) suffering from adv solid tumors harboring an NTRK fusion.
Methods
Larotracking is a real-life registry for pts who initiated L between Apr-2019 and Nov-2020 in French EAP cohort. Eligible pts were > 25 years old pts suffering from adv solid tumors with NTRK fusion using local methodology. Study endpoints were best overall response rate (BORR), progression free and overall survival (PFS and OS) and safety.
Results
Twenty-five pts were enrolled across 15 institutions. Median age at time of L start was 58.2 years [30.8-78.0] and 17 pts were women. Main tumor types were thyroid papillary carcinoma (n=8, 32%), lung carcinoma (n=4, 16%) and glioblastoma (n=2, 8%). The main NTRK fusion were ETV6::NTRK3 (n=7, 28%) and TPM3::NTRK1 (n=3, 12%). Median time from diagnosis of adv cancer to NTRK testing was 3.0 months [-6.8-280.5] and 18 pts (72%) received 0 or 1 line of systemic treatment prior to L start. At time of this analysis (median follow-up 23.0 m (95% CI: 21.6-27.8)), 13 pts had permanently discontinued L, median duration of L treatment was 16.5 months [0.7-30.6+]. Main reason for L discontinuation was disease progression (n=8/13). BORR was 64% (95% CI: 42.5-82.0) with 3 in complete response and 13 in partial response and 18.3 months (95% CI: 5.7-NE) median duration of response. Only 1 pt suffered from 1 serious adverse event. PFS and OS will be presented at the meeting.
Conclusions
These results confirm the high efficacy and favorable safety profile of L. They emphasize the heterogeneity and rarity of concerned pts and the need for collaborative cohorts to better characterize pts and diseases and homogenize appropriate testing.
Clinical trial identification
NCT04814667.
Editorial acknowledgement
Legal entity responsible for the study
Centre Léon Bérard, Lyon, France.
Funding
Bayer HealthCare SAS.
Disclosure
A. Dufresne: Non-Financial Interests, Project Lead, Translational research project: GSK, Adaptimmune; Non-Financial Interests, Project Lead, Translational research program: Bayer. O. Huillard: Financial Interests, Personal, Invited Speaker: Sanofi, IPSEN, Novartis; Financial Interests, Personal, Advisory Board: JANSSEN, Bristol Myers Squibb, AstraZeneca, Pfizer, EISAI, Bayer. M. Geier: Financial Interests, Institutional, Research Grant: BMS, Roche; Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, Sanofi, BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca. J. Wassermann: Financial Interests, Personal, Advisory Board: Bayer, Eisai, Eli Lilly; Financial Interests, Personal, Other, Travel Expenses: Novartis. C. Tournigand: Financial Interests, Institutional, Funding, research project: bayer. D. Perol: Financial Interests, Institutional, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Eli-Lilly, Ipsen, Roche, Novartis, Merck Sharp and Dohme, Takeda. J. Blay: Financial Interests, Personal, Advisory Board: Bayer, Deciphera, GSK, Roche; Financial Interests, Personal, Invited Speaker: Pharmamar; Financial Interests, Institutional, Invited Speaker: MSD, MSD; Financial Interests, Personal, Other, member of the supervisory board: Innate pharma; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. All other authors have declared no conflicts of interest.