Trastuzumab (Herceptin) Increases Overall Survival in HER2-Positive Gastric Cancer

May 31, 2009
Christin Melton

More than 1 million new cases of gastric cancer are diagnosed annually worldwide. The prognosis for patients with this disease is poor, and new treatments with the potential to offer even small improvements in survival can be practice-changing.

More than 1 million new cases of gastric cancer are diagnosed annually worldwide. The prognosis for patients with this disease is poor, and new treatments with the potential to offer even small improvements in survival can be practice-changing. Prior studies have established that approximately 22% of gastric cancers overexpress HER2, a receptor commonly associated with breast cancer. HER2-positive breast tumors are often treated with trastuzumab (Herceptin), a monoclonal antibody that selectively blocks HER2 receptors. Investigators led by Eric Van Cutsem, MD, PhD, University Hospital Gasthuisberg, Leuven, Belgium, found that trastuzumab has the same effect in gastric cancers.

The phase III ToGA trial enrolled 3807 patients from various countries with locally advanced, recurrent, or metastatic gastroesophageal or gastric adenocarcinoma. A subset of 584 patients had HER2-positive tumors. Patients were randomized to receive standard platinum-based chemotherapy alone or in combination with trastuzumab, for 6 cycles. Patients in the trastuzumab-arm continued treatment with this agent until evidence of disease progression. At a median follow-up of 17.1 months, investigators observed median overall survival of 13.8 months in the trastuzumab group versus 11.1 months in the chemotherapy-alone group. “This translates to a 26% lower chance of dying of the cancer when patients are treated with chemo plus trastuzumab compared to chemo alone,” said Dr. Van Cutsem. Overall survival was the primary end point of the trial, and Dr. Van Cutsem said, “The trial clearly met the primary endpoint.” He said results were consistent across all subgroups, including patients with different sites of metastases.

Response rate was a secondary end point, and Dr. Van Cutsem said this was higher in the chemotherapy plus trastuzumab group. Overall response rate was 47.3% in the trastuzumab arm versus 34.5% for patients treated only with chemotherapy. Although the difference in the rate of complete response was not significant, more than twice as many patients who received chemotherapy and trastuzumab achieved complete response, at 5.4% versus 2.4%, respectively (P = .0599).

The study also looked at safety. Dr. Van Cutsem noted that some breast cancer patients treated with trastuzumab develop cardiac problems; this did not happen in the ToGA trial. Dr. Van Cutsem attributed this to the fact that breast cancer patients are often treated with anthracyclines at some point, which have cardiotoxic effects that can last long after treatment discontinuation. Other adverse effects were consistent with those commonly associated with cytotoxic chemotherapy.

Dr. Van Cutsem said the findings were practice changing, adding that “trastuzumab is the first targeted agent, the first biological, to show a survival benefit in advanced gastric cancer.” Somali Smith, MD, who moderated the panel presentation, described the study results as “very exciting,” and affirmed that they were indeed “practice-changing.” Possibilities for future studies, said Dr. Van Cutsem, include the use of trastuzumab in adjuvant treatment and in combination with other agents. Full results of the study will be presented at ASCO on Monday, June 1, at 3:00 PM.

ASCO Abstract #LBA4509.