Policy & Regulation
Enhertu Approved in the U.S. for the Treatment of Patients with Previously Treated HER2 Positive Advanced Gastric Cancer
15 January 2021 - - AstraZeneca Enhertu (fam-trastuzumab deruxtecan-nxki) has been approved in the U.S. for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen, Japanese pharmaceutical company Daiichi Sankyo company, Ltd said.

In the U.S., gastric cancer is more frequently diagnosed in the advanced stage, with only approximately 5% of patients surviving five years.

Approximately one in five gastric cancers are HER2 positive.

Regular approval by the U.S. Food and Drug Administration was based on the positive results from the randomized pivotal DESTINY-Gastric01 phase 2 trial, in which Enhertu demonstrated a statistically significant and clinically meaningful improvement in overall survival and objective response rate versus chemotherapy (irinotecan or paclitaxel) in patients with advanced gastric or GEJ adenocarcinoma who had progressed on at least two prior regimens including trastuzumab, a fluoropyrimidine and a platinum-containing chemotherapy.

In the DESTINY-Gastric01 trial, patients (n=126) in the Enhertu treatment arm 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 with a median OS of 12.5 months [95% CI 9.6-14.3] versus 8.4 months [95% CI 6.9-10.7] with chemotherapy.

Confirmed ORR, assessed by independent central review, was a major efficacy outcome.

Results showed a confirmed ORR of 40.5% [95% CI 31.8-49.6] with Enhertu compared to 11.3% [95% CI 4.7-21.9] with chemotherapy. Patients treated with Enhertu had a 7.9% complete response rate and a 32.5% partial response rate compared to a complete response rate of 0% and a partial response rate of 11.3% for patients treated with chemotherapy. 

Additionally, Enhertu showed a median duration of response of 11.3 months [95% CI 5.6-NR] versus 3.9 months [95% CI 3.0-4.9] with chemotherapy.

Enhertu also demonstrated a median progression-free survival of 5.6 months [95% CI 4.3-6.9] compared to 3.5 months [95% CI 2.0-4.3] (HR=0.47; 95% CI 0.31-0.71) with chemotherapy.

Results from the DESTINY-Gastric01 trial were presented at the 2020 American Society of Clinical Oncology meeting and published in The New England Journal of Medicine.

The safety of Enhertu was evaluated in 187 patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01.

The most common adverse reactions, including laboratory abnormalities, were hemoglobin decreased, white blood cell count decreased, neutrophil count decreased, lymphocyte count decreased, platelet count decreased, nausea, decreased appetite, anemia, aspartate aminotransferase increased, fatigue, blood alkaline phosphatase increased, alanine aminotransferase increased, diarrhea, hypokalemia, vomiting, constipation, blood bilirubin increased, pyrexia, and alopecia.

In DESTINY-Gastric01, of the 125 patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma treated with Enhertu 6.4 mg/kg, interstitial lung disease occurred in 10% of patients.

Median time to first onset of ILD was 2.8 months (range: 1.2 to 21.0).

This is the second regulatory approval for Enhertu in the US Enhertu is also approved in the U.S. under accelerated approval, and in Japan, under the conditional early approval system, for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 trial.

Enhertu is also approved in Japan for HER2 positive unresectable advanced or recurrent gastric cancer that has progressed after chemotherapy based on the DESTINY-Gastric01 trial.

Enhertu previously received Priority Review and Breakthrough Therapy Designation in the U.S. for the treatment of patients with previously treated HER2 positive metastatic gastric cancer, as well as Orphan Drug Designation for patients with gastric cancer, including gastroesophageal junction cancer.

Two additional phase 2 trials, DESTINY-Gastric02 and DESTINY-Gastric03, are underway, further evaluating the use of Enhertu in patients with HER2 positive metastatic gastric cancer.
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