Pertuzumab Plus Trastuzumab in HER2-Amplified Metastatic Colorectal Cancer


Key Points

  • Pertuzumab plus trastuzumab produced a response rate of 32%.
  • Median duration of response was 5.9 months, with some responses of more than 12 months.

As reported in The Lancet Oncology by Meric-Bernstam et al, the combination of pertuzumab and trastuzumab showed activity in HER2-amplified metastatic colorectal cancer in the phase IIa multiple basket study MyPathway. The study is evaluating activity of targeted therapies in nonindicated tumor types with potentially predictive molecular alterations.

Study Details

The study involved a cohort of 57 patients from 25 U.S. sites who had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer with measurable or evaluable disease. Treatment consisted of pertuzumab at an 840 mg loading dose followed by 420 mg every 3 weeks, and trastuzumab at an 8 mg/kg loading dose followed by 6 mg/kg every 3 weeks.

Response Rates

Among the 57 patients, 18 (32%) had objective responses, including complete response in 1 patient. The overall disease control rate was 44%. Response rates were 40% among 43 patients with wild-type KRAS and 43% among 40 patients with wild-type PIK3CA. Median duration of response was 5.9 months, with 4 patients having response of > 12 months. Estimated median progression-free survival was 2.9 months, and estimated median overall survival was 11.5 months.

Adverse Events

The most common adverse events of any grade were diarrhea (33%), fatigue (32%), and nausea (30%). Grade 3 or 4 adverse events occurred in 37% of patients, with the most common being hypokalemia (5%) and abdominal pain (5%). Serious adverse events occurred in 18% of patients.

No treatment-related deaths were observed.

The investigators concluded, “Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer.”

Funda Meric-Bernstam, MD, of the Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by F. Hoffmann-La Roche/Genentech. The study authors' full disclosures can be found at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.