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Research in Review

Rare Form of Colorectal Cancer Responds Well to Precision Medicine

Patients with a specific type of metastatic colorectal cancer who are chemotherapy-resistant benefit from treatment with a gene-targeting regimen.

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Prior research has shown the human epidermal growth factor receptor 2- (HER2) blocking combination of trastuzumab plus lapatinib to inhibit tumor growth of HER2-amplified metastatic colorectal cancer. However, the combination’s effect in patients with HER2-positive disease – a rare form that represents only 3% of the colon cancer population – is unknown.

Italian researchers led by Silvia Marsoni, MD, Istituto di Candiolo (Italy), conducted a study to assess the anti-tumor activity of trastuzumab plus lapatinib in patients with HER2-positive colorectal cancer. A total of 33 heavily pretreated, standard-of-care resistant patients underwent intravenous trastuzumab (4 mg/kg followed by 2 mg/kg once per week) and oral lapatinib (1000 mg/day) until evidence of disease progression. The primary endpoint was objective response rate, defined as complete or partial response. The study was presented at the American Association for Cancer Research annual meeting (April 1-5, 2017).

Results of the showed an overall objective response rate of 30% (95% CI, 14-50) and disease control in 70% of patients. Among the responders, 2 patients demonstrated complete response, with 1 of these complete responders “alive without evidence of disease at almost 36 months from the beginning of treatment,” reported Dr Marsoni in a press conference (April 3, 2017).

Additionally, no grade 3 toxicities were reported and only 1 case of diarrhea was reported. The only other toxicity observed was fatigue among a few patients. Ninety percent of patients were compliant with treatment. “The patient on treatment for 36 months has no complaint whatsoever,” said Dr Marsoni.

Researchers concluded that the combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer.

"This is a sensational observation," noted Hans-Joachim Schmoll, MD, PhD, Martin Luther University of Halle-Wittenberg (Germany), who was not involved in the study (April 3, 2017). "Until now, in advanced colorectal cancer, systemic treatment with chemotherapy… has only very exceptionally induced complete responses in first-line treatment, most of it not long-lasting — and in last-line treatment this has never been reported before." – Zachary Bessette

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