Garcia-Foncillas Jesus, Bokemeyer Carsten, Italiano Antoine, Keating Karen, Paracha Noman, Fellous Marc, Marian Marisca, Fillbrunn Mirko, Gao Wei, Ayyagari Rajeev, Lassen Ulrik
Department of Oncology, Cancer Institute, Fundacion Jimenez Diaz University Hospital, Autonomous University, 28040 Madrid, Spain.
Department of Oncology, Hematology and BMT with Section Penumology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Cancers (Basel). 2022 Mar 31;14(7):1793. doi: 10.3390/cancers14071793.
Information regarding the comparative efficacy of first-generation receptor tyrosine kinase inhibitors is limited. This matching-adjusted indirect comparison (MAIC) evaluated differences in efficacy and safety across larotrectinib and entrectinib trials. Data from clinical trials for larotrectinib (LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431)) and entrectinib (ALKA-372-001 (EudraCT 2012-000148-88), STARTRK-1 (NCT02097810), and STARTRK-2 (NCT02568267)) were used. Adults (≥18 years) across trials were matched on available baseline characteristics. Outcomes evaluated included overall response rate (ORR), complete response (CR) rate, duration of response (DoR), overall survival (OS), progression-free survival (PFS), any serious treatment-related adverse events of grade ≥ 3 (TRAEs), and TRAEs leading to treatment discontinuation. The MAIC included 74 patients from entrectinib trials and 117 and 147 patients for the larotrectinib efficacy and safety populations, respectively. Post-matching, larotrectinib was associated with a significantly longer median duration of OS than entrectinib (p < 0.05) and a numerically longer median PFS (p = 0.07). ORR was similar for both agents (p = 0.63). The CR rate was higher (p < 0.05) and the DoR was longer for larotrectinib (p < 0.05). Safety outcomes were comparable and low for both treatments. Results were consistent in sensitivity analyses. These findings suggest favorable efficacy for larotrectinib and comparable safety profiles versus entrectinib in treating tropomyosin receptor kinase fusion cancer.
关于第一代受体酪氨酸激酶抑制剂的比较疗效的信息有限。这项匹配调整间接比较（MAIC）评估了拉罗替尼和恩曲替尼试验在疗效和安全性方面的差异。使用了拉罗替尼（LOXO-TRK-14001（NCT02122913）、SCOUT（NCT02637687）和NAVIGATE（NCT02576431））以及恩曲替尼（ALKA-372-001（EudraCT 2012-000148-88）、STARTRK-1（NCT02097810）和STARTRK-2（NCT02568267））临床试验的数据。各试验中的成年人（≥18岁）根据可用的基线特征进行匹配。评估的结果包括总缓解率（ORR）、完全缓解（CR）率、缓解持续时间（DoR）、总生存期（OS）、无进展生存期（PFS）、任何≥3级严重治疗相关不良事件（TRAEs）以及导致治疗中断的TRAEs。MAIC纳入了恩曲替尼试验的74名患者，拉罗替尼疗效和安全性人群分别为117名和147名患者。匹配后，拉罗替尼的中位OS持续时间显著长于恩曲替尼（p<0.05），中位PFS在数值上也更长（p=0.07）。两种药物的ORR相似（p=0.63）。拉罗替尼的CR率更高（p<0.05），DoR更长（p<0.05）。两种治疗的安全性结果相当且较低。敏感性分析结果一致。这些发现表明，在治疗原肌球蛋白受体激酶融合癌方面，拉罗替尼疗效良好，与恩曲替尼的安全性相当。
