Pertuzumab + trastuzumab for HER2-amplified/overexpressed metastatic colorectal cancer (mCRC): Interim data from MyPathway.

Abstract

676 Background: Among recent advances in precision medicine, HER2 has emerged as a potential therapeutic target for advanced colon cancer. MyPathway is a multi-basket study evaluating the efficacy and safety of targeted therapies in non-indicated tumor types harboring relevant genetic alterations. We present updated data for an expanded cohort of patients with HER2-amplified/overexpressed mCRC receiving HER2-targeted therapy with pertuzumab + trastuzumab. Methods: MyPathway (NCT02091141) is a multicenter, open-label, phase IIA study. Patients in this analysis had treatment-refractory HER2-amplified/overexpressed mCRC by gene sequencing, FISH, or IHC. Patients received standard doses of pertuzumab + trastuzumab until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed overall response rate. The cutoff date was July 31, 2016. Results: Of 34 patients with mCRC enrolled, 32 have had ≥1 tumor assessment. At a median follow-up of 5.2 (range 0.7–18.3) months from treatment initiation, 12 patients had partial responses (PR), with stable disease (SD) for >4 months in 3 additional patients (Table). The safety profiles were consistent with the product labels. Conclusions: Interim data show that HER2-targeted therapy with pertuzumab + trastuzumab, a chemotherapy-free regimen, is active in heavily pretreated HER2-amplified/overexpressed mCRC. The ORR was 37.5%, responses were durable (median 11.1 months), and the CBR was 46.9%. Accrual to MyPathway is ongoing. Clinical trial information: NCT02091141. [Table: see text]