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Pertuzumab–Trastuzumab Combo Yields Promising Results in Metastatic CRC

Dual therapy with pertuzumab and trastuzumab was shown to be well-tolerated in a recent phase 2a clinical trial and could potentially represent a therapy option for heavily pretreated patients with HER2-amplified metastatic colorectal cancer (Lancet Oncol. 2019 Mar 8. Epub ahead of print).

“Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric cancers, and are emerging as potential treatments for HER2-positive metastatic colorectal cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations,” explained lead investigator Funda Meric-Bernstam, MD, and colleagues, who sought to determine the activity of pertuzumab and trastuzumab in patients with HER2-amplified metastatic colorectal cancer.

The ongoing, multi-basket MyPathway study includes 57 patients with treatment-refractory, histologically confirmed, HER2-amplified, metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status score ≤2. These patients were enrolled at 25 hospitals and clinics across the United States between October 20, 2014, and June 22, 2017.

Patients in the study were given pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) and trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks). The primary end point of MyPathway is the percentage of patients who achieving an objective response per investigator-reported tumor responses.

As of August 1, 2017, 1 (2%) patient had achieved a complete response and 17 (30%) had achieved partial responses, resulting in 18 patients overall achieving an objective response (32%, 95% confidence interval, 20-45).

Diarrhea (33%), fatigue (32%), and nausea (30%) were the most frequently reported treatment-emergent adverse events. A total of 21 (37%) patients experienced grade 3-4 treatment-emergent adverse events, the most common of which were hypokalemia and abdominal pain (each occurring in 5%).

Approximately 20% of patients had serious treatment-emergent adverse events, 2 of which were considered treatment-related (ie, chills and infusion-related reaction).

Dr Meric-Bernstam and colleagues reported that there were no treatment-related deaths.

“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,” they concluded.—Hina Khaliq

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