New drug combination boosts survival in advanced stomach and esophageal cancers

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Patients whose metastatic stomach or esophageal cancers were driven by a mutated HER2 gene had markedly improved response rates and survival when bevacizumab (Avastin) was added to a standard drug combination. Scientists at Dana-Farber Cancer Institute, who led the research, will report these findings at the annual meeting of the American Society of Clinical Oncology (ASCO) on Monday, June 1, 2015.

Of the 36 patients in the phase 2 trial, the median overall survival thus far is at least 21 months, reported Peter Enzinger, MD, of Dana-Farber. He is clinical director of the Center for Esophageal and Gastric Cancer at Dana-Farber/Brigham and Women’s Cancer Center. The response rate was 81 percent, including 25 partial and two complete responses.

Bevacizumab, an anti-angiogenesis agent, was added to the combination of capecitabine and oxaliplatin chemotherapy and trastuzumab (Herceptin). This combination is known as CAPOX+B+T. Trastuzumab blocks the growth-stimulating effects of the HER2mutation that is present in 15 to 20 percent of patients with esophageal and gastric cancer.

In a previous trial, similar patients treated with a combination of trastuzumab, capecitabine, and cisplatin (but not bevacizumab) had an overall survival of 13.8 months and a 47 percent response rate. Several of the initial patients in the trial who began treatment as early as January 2012 are still alive, noted Enzinger.

Of the patients treated with CAPOX+B+T, tumors were found in the esophagus, stomach, and in the junction between the esophagus and stomach.

The drug combination was well tolerated, the researchers said: 16 patients needed to have their doses modified.

“I think this combination has promise,” said Enzinger, noting that “there appears to be at least an additive effect between bevacizumab and trastuzumab. He said he hopes that a large, randomized phase 2 trial can be launched to confirm the findings of this smaller study.

The research was supported by Genentech.

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Esophageal Cancer
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