No abstract

36 Background: ML28897 (MyPathway) is a multi-basket trial evaluating the efficacy and safety of targeted therapies in non-indicated tumor types harboring relevant genetic alterations. In MyPathway, patients with treatment-refractory HER2-amplified metastatic colorectal cancer (mCRC) were enrolled and received pertuzumab plus trastuzumab. In order to facilitate contextualization of the outcome of pertuzumab plus trastuzumab in MyPathway, we conducted a retrospective study to compare with the outcome in real-world HER2-amplified mCRC patients. Methods: Overall survival (OS) was used as the endpoint to compare outcomes from MyPathway (PER/HER arm) and the external control of HER2-amplified mCRC patients treated with any therapy except anti-HER2 therapy in the refractory setting (EC arm) from the US-based de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB). The de-identified data originated from approximately 280 US cancer clinics (̃800 sites of care). OS was defined as time from first treatment to death in the PER/HER arm and from index date (initiation of treatment in the refractory setting) to death in the EC arm. For patients in the CGDB who had met study eligibility criteria at multiple index dates, all eligible index dates were used for the analysis. Standardized mortality ratio weighting based on propensity score was used for deriving the pseudo-population (post-weighting population). In the post-weighting population, multivariate Cox regression models and Kaplan-Meier analyses were used to compare between the arms. A series of sensitivity analyses were conducted to investigate the robustness and consistency of the primary analysis results. Results: The PER/HER arm consisted of 57 patients who had treatment-refractory mCRC with HER2 amplification and enrolled in the MyPathway by August 1, 2017 data cutoff. For the EC arm, 64 HER2-amplified mCRC patients were selected from CGDB collected between January 1, 2011 and December 31, 2019. After applying the predefined inclusion/exclusion criteria set to be similar to those in the MyPathway, 27 eligible index dates were selected from 18 eligible patients and used for primary analysis. In the post-weighting population, the hazard ratio (HR) for OS estimated by multivariate Cox regression model was 0.729 (95% CI: 0.184-3.900) and median survival in the PER/HER arm and the EC arm were 11.47 months (95% CI: 7.72-22.11) and 9.72 months (95% CI: 7.43-22.21), respectively. The results of the all sensitivity analyses were consistent with those in the primary analysis in terms of the point estimate of HR. Conclusions: Despite a small sample size, the totality of findings suggests that the combination of pertuzumab and trastuzumab could have a potential benefit in OS for this population.