Gastric cancer conjugate drug increases survival by 41% in phase 2 trial

Last Updated: 2020-05-29

By Gene Emery

(Reuters Health) - The antibody drug conjugate trastuzumab deruxtecan improves overall survival by 41% in people with HER2-positive gastric cancer compared to conventional chemotherapy, according to the results of an open-label phase 2 test of 187 volunteers reported Friday.

Details of the DESTINY-Gastric01 study were released online during the American Society of Clinical Oncology's 2020 Virtual Scientific Program and published by The New England Journal of Medicine.

Japan's Daiichi Sankyo, which designed and paid for the study, had previously announced, without offering specifics, that the treatment had produced a meaningful improvement in the objective response rate and a significant increase in overall survival.

Median overall survival was 12.5 months for the 125 volunteers from Japan and South Korea who received the treatment - a combination of an anti-HER2 antibody, a cleavable tetrapeptide-based linker and a cytotoxic topoisomerase 1 inhibitor.

In the control group, where the 62 patients received their physician's choice of chemotherapy, median overall survival was 8.4 months (P=0.01).

The objective response rate was 51% with trastuzumab deruxtecan versus 14% with physician's choice therapy (P<0.001).

Before the test, all of the patients had seen their gastric or gastroesophageal junction adenocarcinoma progress after having received at least two previous therapies.

An estimated 15% to 20% of such tumors are HER2 positive.

The research team, led by Dr. Kohei Shitara of the National Cancer Center Hospital East in Kashiwa, Japan, estimated that the overall survival at 12 months would be 52% with trastuzumab deruxtecan versus 29% in the physician's choice group.

However, neutrophil counts declined significantly in 51% of patients receiving the drug conjugate, compared with 24% of patients receiving other therapies, most frequently irinotecan or, in 7 cases, paclitaxel.

In addition, the experimental treatment produced interstitial lung disease or pneumonia in nearly 10% of patients, including one death due to the pneumonia.

The drug conjugate, also known by the brand name Enhertu, is being sold outside Japan by AstraZeneca. The U.S. Food and Drug Administration has approved it for use against unresectable or metastatic HER2-positive breast cancer in patients who were not helped by at least two other anti-HER2-based regimens. It is given as an intravenous infusion every 3 weeks.

SOURCE: https://bit.ly/2ZKBZDv The New England Journal of Medicine, online May 29, 2020