Division of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Centre Léon Bérard, UNICANCER, Université Claude Bernard Lyon, Lyon, France.
ESMO Open. 2021 Apr;6(2):100072. doi: 10.1016/j.esmoop.2021.100072. Epub 2021 Mar 4.
Entrectinib is a tropomyosin receptor kinase inhibitor approved for the treatment of neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours based on single-arm trials. Traditional randomised clinical trials in rare cancers are not feasible; we conducted an intrapatient analysis to evaluate the clinical benefit of entrectinib versus prior standard-of-care systemic therapies.
Patients with locally advanced/metastatic NTRK fusion-positive tumours enrolled in the global phase II, single-arm STARTRK-2 trial were grouped according to prior systemic therapy and response. The key analysis used growth modulation index [GMI; ratio of progression-free survival (PFS) on entrectinib to time to discontinuation (TTD) on the most recent prior therapy]; ratio ≥1.3 indicated clinically meaningful efficacy. Additional analyses investigated TTD and objective response rate (ORR) for entrectinib and prior therapies.
Seventy-one patients were included; 51 received prior systemic therapy. In 38 patients who progressed on prior therapy, ORR was 60.5% (23/38) with entrectinib and 15.8% (6/38) with the most recent prior therapy. Median PFS [11.2 months; 95% confidence interval (CI) 6.7-not estimable] for entrectinib exceeded median TTD (2.9 months; 95% CI 2.0-4.9) for most recent prior therapy. From the intrapatient analysis of GMI, 65.8% had a ratio ≥1.3 and median GMI was 2.53. Consistent results were observed at more stringent GMI thresholds; 60.5% of patients had GMI ≥1.5 or ≥1.8 and 57.9% had GMI ≥2.0.
ORR was high and PFS was longer on entrectinib versus TTD on prior therapy. Furthermore, 65.8% of patients experienced clinically meaningful benefit based on GMI. This intrapatient analysis demonstrates comparative effectiveness of entrectinib in a rare, heterogeneous adult population.
恩曲替尼是一种原肌球蛋白受体激酶抑制剂，基于单臂试验获批用于治疗神经营养酪氨酸受体激酶（NTRK）融合阳性实体瘤。在罕见癌症中进行传统的随机临床试验是不可行的；我们进行了一项患者内分析，以评估恩曲替尼与先前标准治疗系统疗法相比的临床获益。
在全球 II 期、单臂 STARTRK-2 试验中入组的局部晚期/转移性 NTRK 融合阳性肿瘤患者，根据先前的系统治疗和反应进行分组。主要分析采用生长调节指数[GMI；恩曲替尼无进展生存期（PFS）与最近一次先前治疗停药时间（TTD）的比值]；比值≥1.3 表示具有临床意义的疗效。还进行了其他分析，以评估恩曲替尼和先前治疗的 TTD 和客观缓解率（ORR）。
共纳入 71 例患者；51 例患者接受了先前的系统治疗。在 38 例先前治疗进展的患者中，恩曲替尼的 ORR 为 60.5%（23/38），而最近一次先前治疗的 ORR 为 15.8%（6/38）。恩曲替尼的中位 PFS[11.2 个月；95%置信区间（CI）6.7-不可估计]超过了最近一次先前治疗的中位 TTD（2.9 个月；95%CI 2.0-4.9）。从患者内 GMI 分析来看，65.8%的患者比值≥1.3，中位 GMI 为 2.53。在更严格的 GMI 阈值下观察到了一致的结果；60.5%的患者 GMI≥1.5 或≥1.8，57.9%的患者 GMI≥2.0。
与先前治疗的 TTD 相比，恩曲替尼的 ORR 较高，PFS 较长。此外，65.8%的患者根据 GMI 观察到具有临床意义的获益。这项患者内分析证明了恩曲替尼在罕见的、异质的成年人群中的比较有效性。
