Enhertu significantly improved tumour response rate and overall survival in HER2-positive metastatic gastric cancer in Phase II DESTINY-Gastric01 trial .- AstraZeneca + Daiichi Sankyo.

Detailed results from the positive, registrational, randomised controlled Phase II DESTINY-Gastric01 trial showed AstraZeneca and Daiichi Sankyo Company, Limited (Daiichi Sankyo)’s Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR) and overall survival (OS) , a key secondary endpoint, versus chemotherapy.

The trial evaluated patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma that had progressed following two or more treatment regimens including trastuzumab and chemotherapy. Gastric cancer is the third leading cause of cancer mortality with a five-year survival rate of 5% for metastatic disease. Approximately one in five gastric cancers are considered HER2 positive.

The confirmed ORR, assessed by independent central review, was 42.9% with Enhertu monotherapy (6.4mg/kg) compared to 12.5% with investigator’s choice of chemotherapy (paclitaxel or irinotecan) . Ten complete responses (CRs) and 41 partial responses (PRs) were seen in patients treated with Enhertu versus no CRs and seven PRs seen in patients treated with chemotherapy. Patients treated with Enhertu had a 41% reduction in the risk of death versus patients treated with chemotherapy (based on a hazard ratio [HR] of 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097) at a pre-specified interim analysis. The median OS was 12.5 months versus 8.4 months with chemotherapy. The estimated OS rate at one year in the Enhertu arm was 52.1% and 28.9% with the chemotherapy arm.

Kohei Shitara, MD, Chief of Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan and principal investigator in the Phase II DESTINY-Gastric01 trial, said: “Once patients with HER2-positive metastatic gastric cancer progress following initial treatment with an anti-HER2 regimen, there are limited options and no approved HER2-targeted therapies. Based on the compelling results of the DESTINY-Gastric01 trial, Enhertu has the potential to become a new standard of care for these patients.”

Enhertu showed a confirmed disease control rate (DCR) of 85.7% versus 62.5% and a median confirmed duration of response (DoR) of 11.3 months versus 3.9 months with chemotherapy..

The safety and tolerability profile of Enhertu in DESTINY-Gastric01 was consistent with that observed in the Phase I gastric cancer trial and previously reported Enhertu trials.

The most common Grade 3 or higher treatment-emergent adverse events were decreased neutrophil count (51.2%), anaemia (37.6%), decreased white blood cell count (20.8%) and decreased appetite (16.8%). There were 12 cases (9.6%) of confirmed treatment-related interstitial lung disease (ILD) and pneumonitis as determined by an independent review. The majority were Grade 1 or 2 with two Grade 3, one Grade 4 and no Grade 5 (ILD-related deaths). The results were presented during the 2020 American Society of Clinical Oncology ASCO20 Virtual Scientific Program and simultaneously published online in The New England Journal of Medicine.

See- ” Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer”.Kohei Shitara, M.D., Yung-Jue Bang, M.D., Ph.D., Satoru Iwasa, M.D., Ph.D., et al., for the DESTINY-Gastric01 Investigators.. May 29, 2020
DOI: 10.1056/NEJMoa2004413.