Enhertu extends survival in advanced gastric cancer

AstraZeneca and Daiichi Sankyo have reported topline data from a phase 3 trial of Enhertu in advanced HER2-positive gastric cancer that could support wider use of the anti-HER2 drug as a second-line treatment.

The DESTINY-Gastric04 study is comparing Enhertu (trastuzumab deruxtecan) to the combination of Eli Lilly's anti-VEGF antibody Cyramza (ramucirumab) with paclitaxel in adults with HER2-positive gastric or gastro-oesophageal junction (GEJ) adenocarcinoma who have progressed on or after a trastuzumab-containing regimen.

The interim results "demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of overall survival" (OS), according to AZ and Daiichi Sankyo, and will now be shared with regulatory authorities around the world. The trial was unblinded early based on the superior efficacy of Enhertu, according to the two drugmakers.

Enhertu is already approved to treat this type of gastric cancer in more than 65 countries, and in some markets – including the US – its label already allows use as a second-line after trastuzumab, based on data from phase 2 studies comparing the drug to chemotherapy after at least two prior treatment regimes. In other markets, however, the antibody-drug conjugate's label only covers third-line use.

Moreover, the results of DESTINY-Gastric04 will also allow AZ and Daiichi Sankyo to convert conditional approvals for Enhertu in gastric cancer in some markets, including the US, to a full license.

Ken Takeshita, Daiichi Sankyo's global head of R&D, pointed out that Enhertu is "the first HER2-directed medicine to demonstrate an improvement in overall survival in a randomised phase 3 trial in the second-line metastatic setting of patients with HER2-positive gastric cancer."

Gastric cancer is associated with a poor prognosis, particularly in the advanced stages of the disease, with only 5% to 10% of metastatic patients surviving five years. Approximately one million cases of gastric cancer were diagnosed in 2022, and around one in five cases are HER2-positive.

Anti-HER2 antibody trastuzumab with chemo is the standard first-line treatment in most markets. Treatment options are few if the disease progresses and do not currently include any HER2-directed therapies.

Enhertu already has seven FDA approvals across breast cancer, gastric cancer, non-small cell lung cancer (NSCLC), and advanced HER2-positive solid tumours, which have driven sales to more than $3.75 billion in 2024, up from $2.57 billion in the prior year.

AZ paid $1.35 billion upfront to license Enhertu from Daiichi Sankyo in 2019 in a deal that could be worth up to $6.9 billion.