Survival Outcomes of Patients With Tropomyosin Receptor Kinase Fusion-Positive Cancer Receiving Larotrectinib Versus Standard of Care: A Matching-Adjusted Indirect Comparison Using Real-World Data

TY - JOUR

T1 - Survival Outcomes of Patients With Tropomyosin Receptor Kinase Fusion-Positive Cancer Receiving Larotrectinib Versus Standard of Care: A Matching-Adjusted Indirect Comparison Using Real-World Data

AU - Bokemeyer, Carsten

AU - Paracha, Noman

AU - Lassen, Ulrik

AU - Italiano, Antoine

AU - Sullivan, Sean D

AU - Marian, Marisca

AU - Brega, Nicoletta

AU - Garcia-Foncillas, Jesus

PY - 2023/1

Y1 - 2023/1

N2 - PURPOSE: Larotrectinib, a highly specific tropomyosin receptor kinase (TRK) inhibitor, previously demonstrated high response rates in single-arm trials of patients with TRK fusion-positive cancer, but there are limited data on comparative effectiveness against standard-of-care (SoC) regimens used in routine health care practice, before widespread adoption of TRK inhibitors as SoC for TRK fusion-positive cancers. Matching-adjusted indirect comparison, 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.MATERIALS AND METHODS: Individual patient data from three larotrectinib trials (ClinicalTrials.gov identifiers: NCT02122913, NCT02637687, and NCT02576431) were compared with published aggregate real-world data from patients with locally advanced/metastatic TRK fusion-positive cancer identified in the Flatiron Health/Foundation Medicine database. OS was defined as the time from advanced/metastatic disease diagnosis to death. After matching population characteristics, the analyses included (1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and (2) estimation of treatment effect of larotrectinib versus non-TRK-inhibitor SoC. These analyses are limited to prognostic variables available in real-world data.RESULTS: Eighty-five larotrectinib patients and 28 non-TRK-inhibitor SoC patients were included in the analyses. After matching, log-rank testing showed no difference in baseline characteristics between the two groups (P = .31). After matching, larotrectinib was associated with a 78% lower risk of death, compared with non-TRK-inhibitor SoC (adjusted hazard ratio, 0.22 [95% CI, 0.09 to 0.52]; P = .001); median OS was 39.7 months (95% CI: 16.4, NE [not estimable]) for larotrectinib and 10.2 months (95% CI: 7.2, 14.1) for SoC.CONCLUSION: Matching-adjusted indirect comparison analyses suggest longer OS with larotrectinib, compared with non-TRK-inhibitor SoC, in adult patients with TRK fusion-positive cancer.

AB - PURPOSE: Larotrectinib, a highly specific tropomyosin receptor kinase (TRK) inhibitor, previously demonstrated high response rates in single-arm trials of patients with TRK fusion-positive cancer, but there are limited data on comparative effectiveness against standard-of-care (SoC) regimens used in routine health care practice, before widespread adoption of TRK inhibitors as SoC for TRK fusion-positive cancers. Matching-adjusted indirect comparison, 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.MATERIALS AND METHODS: Individual patient data from three larotrectinib trials (ClinicalTrials.gov identifiers: NCT02122913, NCT02637687, and NCT02576431) were compared with published aggregate real-world data from patients with locally advanced/metastatic TRK fusion-positive cancer identified in the Flatiron Health/Foundation Medicine database. OS was defined as the time from advanced/metastatic disease diagnosis to death. After matching population characteristics, the analyses included (1) a log-rank test of equality to test whether the two groups were similar before larotrectinib initiation; and (2) estimation of treatment effect of larotrectinib versus non-TRK-inhibitor SoC. These analyses are limited to prognostic variables available in real-world data.RESULTS: Eighty-five larotrectinib patients and 28 non-TRK-inhibitor SoC patients were included in the analyses. After matching, log-rank testing showed no difference in baseline characteristics between the two groups (P = .31). After matching, larotrectinib was associated with a 78% lower risk of death, compared with non-TRK-inhibitor SoC (adjusted hazard ratio, 0.22 [95% CI, 0.09 to 0.52]; P = .001); median OS was 39.7 months (95% CI: 16.4, NE [not estimable]) for larotrectinib and 10.2 months (95% CI: 7.2, 14.1) for SoC.CONCLUSION: Matching-adjusted indirect comparison analyses suggest longer OS with larotrectinib, compared with non-TRK-inhibitor SoC, in adult patients with TRK fusion-positive cancer.

KW - Adult

KW - Humans

KW - Tropomyosin/therapeutic use

KW - Standard of Care

KW - Neoplasms/drug therapy

KW - Pyrimidines/therapeutic use

KW - Antineoplastic Agents/therapeutic use

KW - Protein Kinase Inhibitors/therapeutic use

U2 - 10.1200/PO.22.00436

DO - 10.1200/PO.22.00436

M3 - SCORING: Journal article

C2 - 36689698

VL - 7

SP - e2200436

JO - JCO PRECIS ONCOL

JF - JCO PRECIS ONCOL

SN - 2473-4284

ER -