Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
Roche Products Ltd, Welwyn, Garden City, United Kingdom.
JCO Clin Cancer Inform. 2022 May;6:e2200022. doi: 10.1200/CCI.22.00022.
We compared overall survival (OS) in patients with human epidermal growth factor receptor 2 ()-amplified, treatment-refractory metastatic colorectal cancer (mCRC) receiving pertuzumab plus trastuzumab (PER-HER) in the phase IIa MyPathway multibasket study (ClinicalTrials.gov identifier: NCT02091141) with OS in those receiving routine clinical care in an electronic health record-derived external control arm.
A noninterventional study was conducted using patient-level data from MyPathway participants receiving PER-HER and real-world patients with -amplified treatment-refractory mCRC receiving routine clinical care. This study used a deidentified US-based clinico-genomic database (CGDB). For patients in the CGDB who met study eligibility criteria at multiple index dates (treatment initiation dates in the treatment-refractory setting), all eligible index dates were used for the analysis. Standardized mortality ratio weighting on the basis of propensity score derived a pseudopopulation (postweighting population) balancing key prognostic variables between arms. Multivariate Cox proportional hazards models were used for estimation of the hazard ratio (HR) in the primary OS analysis. A series of sensitivity analyses were conducted to investigate the robustness and consistency of the primary analysis.
The PER-HER arm comprised 57 patients enrolled in the MyPathway study by August 1, 2017 (data cutoff); the external control arm comprised 18 patients (27 index dates) with -amplified mCRC who met the major MyPathway eligibility criteria in CGDB collected between 2011 and 2019. The estimated HR for OS from the multivariate Cox proportional hazards model in the postweighting population was 0.729 (95% CI, 0.184 to 3.900). The results of sensitivity analyses were consistent with the primary analysis in terms of the point estimate of HR.
Despite a small sample size, these findings suggest that PER-HER could have a potential OS benefit for this population.
我们比较了在接受曲妥珠单抗联合帕妥珠单抗（PER-HER）治疗的人表皮生长因子受体 2 () 扩增、治疗耐药转移性结直肠癌（mCRC）患者中，无进展生存期（OS）与接受常规临床护理的电子病历衍生外部对照臂中患者的 OS。这项研究在 IIa 期 MyPathway 多篮子研究（ClinicalTrials.gov 标识符：NCT02091141）中进行。
使用来自接受 PER-HER 的 MyPathway 参与者的患者水平数据和接受常规临床护理的 - 扩增治疗耐药 mCRC 的真实世界患者进行了一项非干预性研究。该研究使用了基于美国的无标识符临床基因组数据库（CGDB）。对于在多个索引日期（治疗耐药环境中的治疗开始日期）符合研究纳入标准的 CGDB 中的患者，所有符合条件的索引日期都用于分析。基于倾向评分的标准化死亡率比加权构建了一个伪人群（后加权人群），以平衡臂之间的关键预后变量。多变量 Cox 比例风险模型用于主要 OS 分析中的风险比（HR）估计。进行了一系列敏感性分析，以调查主要分析的稳健性和一致性。
PER-HER 臂包括 2017 年 8 月 1 日之前入组 MyPathway 研究的 57 名患者（数据截止日期）；外部对照臂包括在 CGDB 中收集的 18 名（27 个索引日期）患有 - 扩增 mCRC 的患者，他们符合 MyPathway 的主要纳入标准，这些患者的数据收集时间为 2011 年至 2019 年。在加权后人群中，多变量 Cox 比例风险模型的 OS 估计 HR 为 0.729（95%CI，0.184 至 3.900）。敏感性分析的结果与主要分析的 HR 点估计一致。
尽管样本量较小，但这些发现表明 PER-HER 可能对该人群具有潜在的 OS 获益。
