Abstract 104P
Background
Information regarding the comparative efficacy and safety of first-generation treatments for Neurotrophic Tropomyosin Receptor Kinase (NTRK) fusion cancer is limited. Although cross-trial comparisons are subject to potential biases, a matching-adjusted indirect comparison (MAIC) can balance observed population characteristics to facilitate comparisons between trials. This study compared larotrectinib and entrectinib using MAIC.
Methods
Adult (≥ 18 years) patient data from larotrectinib trials (LOXO-TRK-14001, SCOUT, and NAVIGATE; data cutoff July 2020) and published aggregate data for entrectinib trials (ALKA-372-001, STARTRK-1, and STARTRK-2; data cutoff October 2018) were used. Patients were matched on available common baseline characteristics (gender, age, race, ECOG score, select tumor types, metastatic disease, NTRK gene, central nervous system metastases, number of prior lines of therapy). Outcomes of interest included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), complete response (CR) rate, duration of response (DoR), any serious treatment-related adverse events (TRAEs), and TRAEs leading to treatment discontinuation. Risk differences (RD) and hazard ratios (HRs) were used to compare treatments.
Results
117 patients from larotrectinib’s efficacy population and 147 from its safety population, and 74 from the entrectinib trials were included. Median follow-up was 16.9 months for larotrectinib and 14.2 months for entrectinib. After matching, larotrectinib was associated with longer OS (p<0.05) and numerically longer PFS (p=0.07, Table). The ORRs were similar (p=0.61). The CR rate was higher (p<0.05) and DoR was longer for larotrectinib (p<0.05). Safety outcomes were comparable and low for both agents.
Conclusions
These findings suggest favorable efficacy of larotrectinib (OS, DoR, and CR) in NTRK fusion cancer compared to entrectinib. Table: 104P
Analysis results
| Entrectinib Larotrectinib | ||||
| Before matching | After matching | |||
| p-value after matching | ||||
| Efficacy Effective sample size (ESS=71.8) | ||||
| OS median (95% CI), months | 23.9 (16.0, -) | Not reached (NR) (40.7, -) | NR (38.7, -) | <0.05 |
| PFS median (95% CI), months | 11.2 (8.0, 15.7) | 33.0 (16.6, -) | 19.3 (11.1, 55.7) | 0.07 |
| DoR median (95% CI), months | 12.9 (9.3, -) | 41.5 (32.5, -) | 32.5 (17.4, -) | <0.05 |
| ORR (95% CI), % | 63.5 (51.5, 74.4) | 65.0 (56.1, 73.2) | 67.6 (55.8, 77.5) | 0.61 |
| CR (95% CI), % | 6.8 (2.2, 15.1) | 19.7 (13.2, 27.5) | 20.6 (13.0, 31.1) | <0.05 |
| Safety (ESS=90.7) | ||||
| Serious TRAE, % | 10.0 (4.2, 20.1) | 5.4 (2.5, 9.9) | 6.2 (2.9, 12.6) | 0.38 |
| TRAEs leading to discontinuation, % | 4.0 (0.9, 12.4) | 0.7 (0.0, 3.0) | 0.5 (0.1, 3.4) | 0.15 |
-: not evaluable.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Bayer, Pharmaceuticals Division.
Funding
Bayer, Pharmaceuticals Division.
Disclosure
J. Garcia-Foncillas: Financial Interests, Research Grant: Merck; Financial Interests, Research Grant: Roche; Financial Interests, Other, advisory boards/speaker’s bureau: AstraZeneca; Financial Interests, Other, advisory boards/speaker’s bureau: Bayer; Financial Interests, Other, advisory boards/speaker’s bureau boards/speaker’s bureau: BMS; Financial Interests, Other, advisory boards/speaker’s bureau: Eli Lilly; Financial Interests, Other, advisory boards/speaker’s bureau: Janssen; Financial Interests, Other, advisory boards/speaker’s bureau: Merck MSD; Financial Interests, Other, advisory boards/speaker’s bureau: Novartis; Financial Interests, Other, advisory boards/speaker’s bureau: Pfizer; Financial Interests, Other, advisory boards/speaker’s bureau: Roche. C. Bokemeyer: Financial Interests, Advisory Board: Sanofi Aventis; Financial Interests, Advisory Board: Merck KGaA; Financial Interests, Advisory Board: Bristol Myers Squibb; Financial Interests, Advisory Board: Merck Sharp & Dohme; Financial Interests, Advisory Board: Bayer Healthcare; Financial Interests, Advisory Board: Novartis; Financial Interests, Other, Consulting: Lilly Imclone; Financial Interests, Other, Consulting: GSO Contract Research; Financial Interests, Other, Consulting: AOK Rheinland-Hamburg. A. Italiano: Financial Interests, Advisory Role: Bayer. K. Keating: Financial Interests, Full or part-time Employment: Bayer. N. Paracha: Financial Interests, Full or part-time Employment: Bayer; Financial Interests, Stocks/Shares: Bayer; Financial Interests, Stocks/Shares: Roche. M. Fellous: Financial Interests, Full or part-time Employment: Bayer. M. Marian: Financial Interests, Full or part-time Employment: Bayer. M. Fillbrunn: Other, Full or part-time Employment, No financial interest in products/processes of this research; Bayer paid AG consulting fees: Analysis Group, Inc. W. Gao: Other, Full or part-time Employment, No financial interest in products/processes of this research; Bayer paid AG consulting fees: Analysis Group, Inc. R. Ayyagari: Other, Full or part-time Employment, No financial interest in products/processes of this research; Bayer paid AG consulting fees: Analysis Group, Inc. U.N. Lassen: Financial Interests, Research Grant: BMS; Financial Interests, Research Grant: GSK; Financial Interests, Research Grant: Pfizer; Financial Interests, Research Grant: Roche; Financial Interests, Advisory Board: Bayer; Financial Interests, Advisory Board: Novartis; Financial Interests, Advisory Board: Pfizer.