Abstract 508P
Background
Larotrectinib is a highly specific tropomyosin receptor kinase (TRK) inhibitor that has demonstrated high response rates in single-arm trials of patients with TRK fusion-positive cancer. There are limited data on their relative efficacy compared to standard-of-care (SoC) regimens used in routine clinical practice before the widespread adoption of TRK inhibitors as SoC for TRK fusion-positive cancers. Matching-adjusted indirect comparison (MAIC), a validated methodology that balances population characteristics to facilitate cross-trial comparisons, was used to compare the overall survival (OS) of larotrectinib versus non-TRK-inhibitor SoC.
Methods
Individual adult patient data from three larotrectinib trials (ClinicalTrials.gov: NCT02122913, NCT02637687, and NCT02576431), July 2023 cut off, were compared with published aggregate real-world data from patients aged ≥18 years with locally advanced/metastatic TRK fusion-positive cancer identified in the Hartwig Medical Foundation database. OS was defined as the time from start of first post-biopsy treatment (or larotrectinib) to death. The two patient populations were matched on clinical characteristics that were available in the real-world data and the treatment effect of larotrectinib versus non–TRK-inhibitor SoC was estimated.
Results
Twenty-four non-TRK-inhibitor SoC and 120 larotrectinib patients were included in the analyses. After matching, median OS was 50.3 months (IQR: 23.3, not estimable) for larotrectinib compared with 13 months (IQR: 6.4, 18.3) for SoC, and larotrectinib was associated with an 84% risk reduction of death (adjusted hazard ratio: 0.16, 95%CI: 0.07 to 0.36). Restricted mean survival conducted up to 26.2 months (the largest observed event time in the SoC arm) was 22.6 for larotrectinib and 12.8 months for SoC (mean difference: 9.8 months, 95% CI: 5.6 to 14.0).
Conclusions
This analysis suggests longer OS with larotrectinib, compared with non–TRK-inhibitor SoC, in adult patients with TRK fusion-positive cancer. These findings support a previous MAIC conducted using real-world data in this population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Bayer Pharmaceuticals.
Funding
Bayer Pharmaceuticals.
Disclosure
C. Bokemeyer: Financial Interests, Personal, Advisory Board, advisory boards and speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Roche Pharma, AOK Germany, Med update; Financial Interests, Personal, Advisory Board: Bayer Healthcare, Oncology Drug Consult CRO, Lindis Biotech, BioNTech; Financial Interests, Personal, Advisory Board, Boards attended and lectures given: Sanofi Aventis; Financial Interests, Personal, Advisory Board, advisory board and speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker, orgaistion for medical education: med update; Financial Interests, Institutional, Local PI, our department is involved in several clincal trials sponsored by industry and cooperative groups where we hold praticipants roles and local PI roles and PI roles: more than 95 clinical trials; Non-Financial Interests, Personal, Advisory Role: DGHO; Non-Financial Interests, Personal, Leadership Role: Hamburg Cancer Society, National Network of German Cancer Centers (DKH); Non-Financial Interests, Personal, Member of Board of Directors: Northern German Society of Internal Medicine; Non-Financial Interests, Personal, Advisory Role, Board of DGHO Advisors: DGHO; Non-Financial Interests, Personal, Advisory Role, Board of Directors Oncology Center Certification Committee: German Cancer Society. K. Abrams: Financial Interests, Institutional, Funding: Bayer Pharmaceuticals. J. Garcia-Foncillas: Financial Interests, Institutional, Funding: Bayer Pharmaceuticals; Financial Interests, Institutional, Advisory Board: Bayer pharmaceuticals. A. Italiano: Financial Interests, Institutional, Advisory Board: Bayer Pharmaceuticals; Financial Interests, Institutional, Funding: Bayer Pharmaceuticals. U.N. Lassen: Financial Interests, Personal, Advisory Board: Bayer, Novartis; Financial Interests, Institutional, Research Grant: Roche, BMS, Pfizer, GSK, Lilly, Incyte, Janssen. L. Linsell: Financial Interests, Institutional, Funding: Bayer Pharmaceuticals. M. Marian: Financial Interests, Personal, Full or part-time Employment: Bayer. N. Paracha: Financial Interests, Institutional, Full or part-time Employment: Bayer Pharmaceuticals. S. Sullivan: Financial Interests, Institutional, Advisory Board: Bayer Pharmaceuticals; Financial Interests, Institutional, Funding: Bayer pharmaceuticals. J. Thompson: Financial Interests, Institutional, Funding: Bayer Pharmaceuticals.