University Medical Centre Hamburg Eppendorf, Hamburg, Germany.
Bayer Pharmaceuticals, Basel, Switzerland.
JCO Precis Oncol. 2023 Jan;7:e2200436. doi: 10.1200/PO.22.00436.
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 ( = .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]; = .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.
目的：拉罗替尼是一种高度特异性原肌球蛋白受体激酶（TRK）抑制剂，在 TRK 融合阳性癌症的单臂试验中表现出高反应率，但在广泛采用 TRK 抑制剂作为 TRK 融合阳性癌症的标准治疗（SoC）之前，针对常规医疗实践中使用的标准治疗方案（SoC）的比较有效性数据有限。匹配调整的间接比较是一种经过验证的方法，它可以平衡人群特征，以促进跨试验比较，用于比较拉罗替尼与非 TRK 抑制剂 SoC 的总生存期（OS）。
材料和方法：从三项拉罗替尼试验（ClinicalTrials.gov 标识符：NCT02122913、NCT02637687 和 NCT02576431）中获取个体患者数据，并与 Flatiron Health/Foundation Medicine 数据库中确定的局部晚期/转移性 TRK 融合阳性癌症患者的已发表的真实世界汇总数据进行比较。OS 定义为从晚期/转移性疾病诊断到死亡的时间。在匹配人群特征后，分析包括（1）对数秩检验，以检验在开始拉罗替尼治疗之前两组是否相似；和（2）估计拉罗替尼与非 TRK 抑制剂 SoC 的治疗效果。这些分析仅限于真实世界数据中可用的预后变量。
结果：85 名拉罗替尼患者和 28 名非 TRK 抑制剂 SoC 患者纳入分析。匹配后，两组间基线特征的对数秩检验无差异（ =.31）。匹配后，与非 TRK 抑制剂 SoC 相比，拉罗替尼死亡风险降低 78%，调整后的危险比为 0.22（95%CI，0.09 至 0.52）； =.001）；拉罗替尼的中位 OS 为 39.7 个月（95%CI：16.4，NE[无法估计]），SoC 为 10.2 个月（95%CI：7.2，14.1）。
结论：匹配调整的间接比较分析表明，在 TRK 融合阳性癌症的成年患者中，与非 TRK 抑制剂 SoC 相比，拉罗替尼的 OS 更长。
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