Pertuzumab plus Trastuzumab for HER2-Amplified Colorectal Cancer

Dual-targeted HER2 therapy with pertuzumab and trastuzumab has shown activity in patients with HER2-amplified metastatic colorectal cancer (mCRC; NEJM JW Oncol Hematol May 2019 and Lancet Oncol 2019; 20:518).

To evaluate this approach further, investigators conducted an industry-funded, prospective, phase 2 basket trial (TAPUR) that assessed the use of pertuzumab and trastuzumab in previously treated mCRC patients who had HER2 amplification and/or HER2/3 mutation, the presence of which is seen in only 5% to 10% of mCRC patients. Of the 38 patients in the trial, 74% were HER2-amplified with or without HER2/3 mutation, 26% had only HER2/3 mutation, 68% had left-sided colon or rectal primaries, 84% had received ≥3 prior lines of therapy, and 29% had KRAS mutation.

In the HER2-amplified group, the disease-control rate (the primary end point) was 54%, rejecting the null hypothesis of a 15% disease-control rate, and the objective response rate was 25%. Median progression-free survival was 17.2 weeks, and overall survival was 60.0 weeks. Patients with HER2/3 mutation did not respond to treatment, nor did patients with KRAS or BRAF mutation. No new safety signals were observed.