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Larotrectinib Compared With Real-World Non-Tropomyosin Receptor Kinase Inhibitor Therapies in Patients With
Marcia S Brose1, C Benedikt Westphalen2,3,4, Xiaoyun Pan5
1Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA.
Purpose:
Neurotrophic tyrosine receptor kinase gene fusions are oncogenic drivers of various solid tumors. Larotrectinib is a highly selective tropomyosin receptor kinase (TRK) inhibitor approved for patients with TRK fusion cancer on the basis of single-arm trials. This study was a matched comparative effectiveness study of larotrectinib in clinical trials versus standard of care (SOC) in the real-world (RW) setting.
Methods:
Adult patients with advanced/metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma were included. Deduplicated data from RW patients were from US and ex-US data sources. Patients in the larotrectinib cohort (pooled data from three trials, ClinicalTrials.gov identifiers: NCT02122913, NCT02576431, and NCT02637687) were matched 1:1 to RW patients on the basis of tumor type and line of therapy (LOT). A propensity score (weighting) model was used to balance key characteristics between cohorts. The primary outcome was overall survival (OS).
Results:
In total, 164 patients were matched 1:1 on tumor type and LOT (82 in each cohort). Balance in the baseline covariates was achieved after weighting. Larotrectinib-treated patients had longer OS (median, not reached [NR] v 37.2 months; hazard ratio [HR], 0.44 [95% CI, 0.23 to 0.83]), time to next treatment (median, NR v 10.6 months; HR, 0.22 [95% CI, 0.13 to 0.38]), duration of therapy (median, 30.8 v 3.4 months; HR, 0.23 [95% CI, 0.15 to 0.33]), and progression-free survival (median, 36.8 v 5.2 months; HR, 0.29 [95% CI, 0.18 to 0.46]) compared with RW patients after propensity score weighting.
Conclusion:
In TRK fusion cancers, treatment with larotrectinib was associated with longer OS and prolonged time to event compared with SOC in all categories measured. These RW data provide context to support larotrectinib effectiveness in this population.
Insights
Larotrectinib significantly improved overall survival and time to event outcomes for patients with TRK fusion cancers compared to standard of care in real-world settings. These findings support larotrectinib
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Neurotrophic tyrosine receptor kinase (TRK) gene fusions are key drivers in various solid tumors.
- Larotrectinib is an approved TRK inhibitor based on single-arm trial data.
- Comparative effectiveness of larotrectinib in real-world versus clinical trial settings is not well-established.
Purpose of the Study:
- To compare the effectiveness of larotrectinib in clinical trials against standard of care (SOC) in the real-world (RW) setting for TRK fusion cancers.
- To evaluate overall survival (OS) as the primary outcome in a matched cohort study.
- To assess time to next treatment, duration of therapy, and progression-free survival.
Main Methods:
- A matched comparative effectiveness study design was employed.
- Adult patients with advanced/metastatic TRK fusion cancers were included (non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, salivary gland carcinoma).
- A 1:1 propensity score matching methodology was used to balance larotrectinib clinical trial patients with RW SOC patients based on tumor type and line of therapy.
Main Results:
- A total of 164 patients were matched (82 per cohort) with achieved covariate balance post-weighting.
- Larotrectinib treatment was associated with significantly longer OS (median, not reached vs. 37.2 months; HR, 0.44) compared to SOC.
- Larotrectinib demonstrated superior outcomes in time to next treatment (median, NR vs. 10.6 months; HR, 0.22), duration of therapy (median, 30.8 vs. 3.4 months; HR, 0.23), and progression-free survival (median, 36.8 vs. 5.2 months; HR, 0.29).
Conclusions:
- Larotrectinib treatment is associated with improved overall survival and prolonged time-to-event outcomes compared to standard of care in TRK fusion cancers.
- Real-world data support the effectiveness of larotrectinib in this patient population.
- The findings provide valuable context for the clinical utility of larotrectinib in treating TRK fusion-driven malignancies.
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