Pertuzumab Plus Trastuzumab for Treatment-Refractory HER2-Amplified Metastatic Colorectal Cancer: Comparison of the MyPathway Trial With a Real-World External Control Arm

Abstract

Purpose: We compared overall survival (OS) in patients with human epidermal growth factor receptor 2 (HER2)-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.

Methods: A noninterventional study was conducted using patient-level data from MyPathway participants receiving PER-HER and real-world patients with HER2-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.

Results: 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 HER2-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.

Conclusion: Despite a small sample size, these findings suggest that PER-HER could have a potential OS benefit for this population.

Conflict of interest statement

Yusuke NaritaEmployment: Chugai PharmaStock and Other Ownership Interests: Chugai Pharma Takuya YoshimotoEmployment: Chugai PharmaStock and Other Ownership Interests: Chugai Pharma Tomoyuki NamaiEmployment: Chugai Pharma Takashi AsakawaEmployment: Chugai Pharma Satoe KawakamiEmployment: Chugai Pharma Craig Gower-PageEmployment: Roche, Publicis Health (I), Vifor Pharma (I)Leadership: Vifor Pharma (I)Stock and Other Ownership Interests: RocheTravel, Accommodations, Expenses: Roche Irmarie Reyes-RiveraEmployment: Roche Pharma AGStock and Other Ownership Interests: Roche/GenentechResearch Funding: Roche Pharma AGTravel, Accommodations, Expenses: Roche Pharma AG Arisha PatelEmployment: Genentech/Roche Yoshiaki NakamuraHonoraria: Chugai Pharma, Guardant Health AMEA, MerckResearch Funding: Taiho Pharmaceutical (Inst), Guardant Health (Inst), Genomedia (Inst), Chugai Pharma (Inst), Seattle Genetics (Inst), Roche (Inst)No other potential conflicts of interest were reported.

Figures

FIG 1.

Study design. CGDB, clinico-genomic database; EC, external control; FH, Flatiron Health; FMI, Foundation Medicine Inc; HER2, human epidermal growth factor receptor 2; I/E, inclusion/exclusion; mCRC, metastatic colorectal cancer; PER-HER, pertuzumab plus trastuzumab.

FIG 2.

EC arm patient attrition. CTCAE, Common Terminology Criteria for Adverse Events; EC, external control; ECOG PS, Eastern Cooperative Oncology Group performance status; FMI, Foundation Medicine Inc; HER2, human epidermal growth factor receptor 2; LVEF, left ventricular ejection fraction; mCRC, metastatic colorectal cancer; NCI, National Cancer Institute. aPatients with missing value are allowed to be included.