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Overall survival and multiple time-to-event endpoints were longer with larotrectinib, including time to next treatment, duration of therapy, and progression-free 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survival.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},372336,1790324970,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & 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Therapies in Patients With Tropomyosin Receptor Kinase Fusion Cancer  \nMarcia S. Brose, MD, PhD1 ; C. Benedikt Westphalen, MD2,3,4 ; Xiaoyun Pan, PhD, MS5; Vadim Bernard-Gauthier, PhD6; Milena Kurtinecz, DPhil5; Helen Guo, MSc6; Virginie Aris, PhD5; Neil R. Brett, PhD7; Abdelali Majdi, MD8; Vivek Subbiah, MD9 ; Nathan A. Pennell, MD, PhD10 ; Kenneth L. Kehl, MD, MPH11,12 ; and Alexander Drilon, MD13,14   \nDOI [https://doi.org/10.1200/PO-24-00500](https://doi.org/10.1200/PO-24-00500)  \n\n| ABSTRACT |  |\n| --- | --- |\n| 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. |\n| 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](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) . |\n| 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 progressionfree 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. |\n| 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. |\n\nACCOMPANYING CONTENT  \n Data Supplement  \nAccepted February 21, 2025 Published April 23, 2025  \nJCO Precis Oncol 9:e2400500 © 2025 by American Society of Clinical Oncology  \nCreative Commons Attribution Non-Commercial No Derivatives 4.0 License  \nINTRODUCTION  \nThe tropomyosin receptor kinase (TRK) proteins TRKA, TRKB, and TRKC are encoded by the neurotrophic tyrosine receptor kinase (NTRK) genes NTRK1 , NTRK2 , and NTRK3 , respectively.1 TRK proteins play a key role in nervous system development and function.1 NTRK gene fusions are oncogenicdrivers of various adult and pediatric cancer types.1 ,2 NTRK gene fusions occur with varying frequencies, from up to 90% in rare cancers (eg, secretory breast carcinoma and infantile fibrosarcoma), to \u003C0.5% in more prevalent tumor types (eg, non–small cell lung cancer [NSCLC] and colorectal cancer  \n[CRC]).3 ,4 A previous retrospective study conducted between January 2011 and July 2018 evaluating the prognosis of TRK fusion cancer in the real-world (RW) setting found that patients with tumors that harbor NTRK gene fusions do not have a statistically better or worse prognosis than those patients with NTRK wild-type tumors.5  \nLarotrectinib is a first-in-class, highly selective, central nervous system–active TRK inhibitor. In a pooled analysis of three phase I/II single-arm clinical trials, larotrectinib demonstrated robust and durable","cbCaienHlAvU4V4q","https://ap.wps.com/l/cbCaienHlAvU4V4q","pdf",750104,11,"English","# Abstract\n## Purpose\n## Methods\n## Results\n## Conclusion\n# Introduction\n## TRK biology and gene fusions\n## Larotrectinib background\n# Context\n## Key Objective\n## Knowledge Generated\n## Relevance","[{\"question\":\"What patient population was evaluated in the larotrectinib comparison?\",\"answer\":\"The analysis included adults with advanced or metastatic TRK fusion non-small cell lung cancer, colorectal cancer, soft tissue sarcoma, thyroid cancer, or salivary gland carcinoma.\"},{\"question\":\"How were larotrectinib-treated patients compared with real-world standard of care patients?\",\"answer\":\"Larotrectinib trial data pooled from three studies were matched 1:1 to real-world patients by tumor type and line of therapy, and propensity score (weighting) was used to balance key characteristics.\"},{\"question\":\"Which outcomes showed benefit for larotrectinib in the real-world matched comparison?\",\"answer\":\"Larotrectinib was associated with longer overall survival and prolonged time-to-event outcomes, including time to next treatment, duration of therapy, and progression-free survival.\"}]","Larotrectinib Compared With Real-World Non - Tropomyosin Receptor Kinase Inhibitor Therapies | PDF",1790194277,28]