Brose Marcia S, Westphalen C Benedikt, Pan Xiaoyun, Bernard-Gauthier Vadim, Kurtinecz Milena, Guo Helen, Aris Virginie, Brett Neil R, Majdi Abdelali, Subbiah Vivek, Pennell Nathan A, Kehl Kenneth L, Drilon Alexander
Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA.
Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
JCO Precis Oncol. 2025 Apr;9:e2400500. doi: 10.1200/PO-24-00500. Epub 2025 Apr 23.
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.
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).
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] 37.2 months; hazard ratio [HR], 0.44 [95% CI, 0.23 to 0.83]), time to next treatment (median, NR 10.6 months; HR, 0.22 [95% CI, 0.13 to 0.38]), duration of therapy (median, 30.8 3.4 months; HR, 0.23 [95% CI, 0.15 to 0.33]), and progression-free survival (median, 36.8 5.2 months; HR, 0.29 [95% CI, 0.18 to 0.46]) compared with RW patients after propensity score weighting.
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.
神经营养性酪氨酸受体激酶基因融合是多种实体瘤的致癌驱动因素。拉罗替尼是一种高度选择性的原肌球蛋白受体激酶（TRK）抑制剂，基于单臂试验被批准用于治疗TRK融合癌患者。本研究是一项在临床试验中比较拉罗替尼与真实世界（RW）环境下标准治疗（SOC）效果的配对研究。
纳入患有晚期/转移性TRK融合非小细胞肺癌、结直肠癌、软组织肉瘤、甲状腺癌或唾液腺癌的成年患者。RW患者的去重数据来自美国和美国以外的数据源。拉罗替尼队列中的患者（来自三项试验的汇总数据，ClinicalTrials.gov标识符：NCT02122913、NCT02576431和NCT02637687）根据肿瘤类型和治疗线数（LOT）与RW患者进行1:1配对。使用倾向评分（加权）模型平衡队列之间的关键特征。主要结局是总生存期（OS）。
总共164例患者在肿瘤类型和LOT方面进行了1:1配对（每个队列82例）。加权后实现了基线协变量的平衡。与倾向评分加权后的RW患者相比，接受拉罗替尼治疗的患者的OS更长（中位数，未达到[NR]对37.2个月；风险比[HR]，0.44[95%CI，0.23至0.83]），至下一次治疗时间更长（中位数，NR对1
