Pertuzumab Plus Trastuzumab for Treatment-Refractory HER2-Amplified Metastatic Colorectal Cancer: Comparison of the
Yusuke Narita1, Takuya Yoshimoto1, Tomoyuki Namai1
1Chugai Pharmaceutical Co, Ltd, Tokyo, Japan.
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.
Insights
Pertuzumab plus trastuzumab (PER-HER) may improve overall survival (OS) in patients with HER2-amplified metastatic colorectal cancer (mCRC) refractory to treatment. This study compared PER-HER to standard care, suggesting a potential survival benefit.
Area of Science:
- Oncology
- Clinical Trials
- Genomics
Background:
- Metastatic colorectal cancer (mCRC) with HER2 amplification is a challenging subset.
- Treatment resistance in mCRC necessitates novel therapeutic strategies.
Purpose of the Study:
- To compare overall survival (OS) in patients with HER2-amplified, treatment-refractory mCRC receiving pertuzumab plus trastuzumab (PER-HER).
- To evaluate the efficacy of PER-HER against routine clinical care using an external control arm.
Main Methods:
- A noninterventional study utilized real-world data from a clinico-genomic database (CGDB).
- Propensity score weighting created a balanced pseudopopulation for comparison.
- Multivariate Cox proportional hazards models assessed the hazard ratio (HR) for OS.
Main Results:
- The study included 57 patients in the PER-HER arm and 18 in the external control arm.
- The estimated HR for OS was 0.729 (95% CI, 0.184 to 3.900), favoring PER-HER.
- Sensitivity analyses confirmed the robustness of the primary findings.
Conclusions:
- PER-HER shows potential for improving OS in patients with HER2-amplified, treatment-refractory mCRC.
- Despite a small sample size, the results indicate a possible survival benefit warranting further investigation.
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