Background: Head-to-head evidence comparing repotrectinib against other approved ROS1 tyrosine kinase inhibitors (TKIs) is not currently available. The objective of this study was to indirectly compare progression-free survival (PFS), the objective response rate (ORR), and the duration of response (DoR) for repotrectinib vs. crizotinib and vs. entrectinib in patients with TKI-naïveROS1+locally advanced or metastatic non-small-cell lung cancer (aNSCLC). Methods: Using evidence from a systematic literature review, unanchored matching-adjusted indirect comparisons (MAICs) were used to estimate population-adjusted hazard ratios (HRs) for PFS and DoR and odds ratios (ORs) for ORR for repotrectinib vs. crizotinib and vs. entrectinib among patients with TKI-naïve aNSCLC. The MAICs were adjusted for imbalances in baseline patient characteristics that were pre-specified as being prognostic or predictive of treatment effects. Weighted Cox (for PFS and DoR) and logistic (for ORR) regression models were fit. Supplementary analyses (SAs) explored the impact of missing data and modeling assumptions on effect estimates. Results: The evidence base was formed by TRIDENT-1 EXP-1 (repotrectinib; N = 71), a pooled set of five trials involving crizotinib (N = 273), and the pooled ALKA-372–001/STARTRK-1 and -2 trials (entrectinib; N = 168). After population adjustment, repotrectinib was associated with statistically significant improvements in PFS relative to crizotinib (HR = 0.44; 95% confidence interval [CI]: 0.29, 0.67) and entrectinib (HR = 0.57; 95% CI: 0.36, 0.91). Differences in ORR and DoR were not statistically significant but numerically favored repotrectinib. SAs were consistent with the main analyses across all comparisons. Conclusions: The analysis demonstrated the strong benefits of repotrectinib in PFS, which was robust across different SAs and supported by numerically favorable results for DoR (where available) and ORR. These results, alongside the published TRIDENT-1 clinical data, further support repotrectinib as a potential new standard of care for TKI-naïve patients withROS1+aNSCLC.
背景：目前尚无直接比较瑞普替尼与其他已获批ROS1酪氨酸激酶抑制剂（TKIs）的头对头证据。本研究旨在间接比较瑞普替尼与克唑替尼及恩曲替尼在未经TKI治疗的ROS1阳性局部晚期或转移性非小细胞肺癌（aNSCLC）患者中的无进展生存期（PFS）、客观缓解率（ORR）和缓解持续时间（DoR）。方法：基于系统性文献综述获得的证据，采用非锚定匹配调整间接比较法，在未经TKI治疗的aNSCLC患者中，估计瑞普替尼与克唑替尼及恩曲替尼相比，经人群调整后的PFS和DoR的风险比（HRs）以及ORR的优势比（ORs）。MAIC分析针对预先指定为预后性或治疗效应预测因素的基线患者特征不平衡进行了调整。拟合了加权Cox回归模型（用于PFS和DoR）和逻辑回归模型（用于ORR）。补充分析探讨了缺失数据和模型假设对效应估计的影响。结果：证据基础由TRIDENT-1 EXP-1（瑞普替尼；N = 71）、涉及克唑替尼的五项试验的汇总数据（N = 273）以及汇总的ALKA-372–001/STARTRK-1和-2试验（恩曲替尼；N = 168）构成。经人群调整后，与克唑替尼相比，瑞普替尼与PFS的统计学显著改善相关（HR = 0.44；95%置信区间[CI]：0.29, 0.67），与恩曲替尼相比亦然（HR = 0.57；95% CI：0.36, 0.91）。ORR和DoR的差异无统计学显著性，但在数值上倾向于瑞普替尼。所有比较的补充分析结果均与主要分析一致。结论：该分析证明了瑞普替尼在PFS方面的显著获益，该结果在不同补充分析中均稳健，并得到DoR（在可获得时）和ORR数值上有利结果的支持。这些结果连同已发表的TRIDENT-1临床数据，进一步支持瑞普替尼作为未经TKI治疗的ROS1阳性aNSCLC患者潜在的新标准治疗方案。
Population-Adjusted Indirect Treatment Comparisons of Repotrectinib Among Patients withROS1+NSCLC
肿瘤(癌症)患者之家