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FDA Approves Daiichi Sankyo, AstraZeneca's Enhertu for Gastric, Gastroesophageal Junction Cancer

NEW YORK – The US Food and Drug Administration on Friday approved Daiichi Sankyo and AstraZeneca's antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) for adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction cancer who have previously received a trastuzumab (Genentech's Herceptin)-based treatment.

The FDA approved the new indication based on results from the Phase II DESTINY-Gastric01 trial, which compared trastuzumab deruxtecan to chemotherapy (irinotecan or paclitaxel) in 188 patients with gastric or gastroesophageal cancer who had progressed on at least two prior treatments, including trastuzumab, a fluoropyrimidine, and a platinum-containing chemotherapy. In the trial, patients receiving trastuzumab deruxtecan had a 41 percent lower risk of death compared to those on chemo, with a median overall survival of 12.5 months and 8.4 months, respectively. 

"This approval represents the first time a HER2-directed medicine has demonstrated a significant improvement in survival compared to chemotherapy for patients following initial treatment in the metastatic setting, and it has the potential to become the new standard of care for this patient population," Ronan Kelly, director of the Charles A. Sammons Cancer Center at Baylor University Medical Center, said in a statement.

Objective response rates were 41 percent versus 11 percent, and median progression-free survival was 5.6 months versus 3.5 months in the trastuzumab deruxtecan and chemo arms, respectively. The drug's label contains a boxed warning for interstitial lung disease and embryo-fetal toxicity.

Around 20 percent of gastric cancers patients have HER2-overexpressing tumors. In the trial, patients were considered HER2-positive if they had an immunohistochemistry score of  3+, or if they had an IHC score of 2+ they also had to be in situ hybridization-positive.

In the US, the drug is already approved for patients with unresectable or metastatic, HER2-positive breast cancer patients after they've received at least two other HER2-directed regimens for metastatic disease. "This second indication in the US represents an important step forward in our ambitious plan to accelerate the development of Enhertu across a broad range of HER2-targetable cancers," Antoine Yver, executive VP and global head of oncology R&D at Daiichi Sankyo, said in a statement.

Daiichi Sankyo and AstraZeneca are also studying trastuzumab deruxtecan in DESTINY-Gastric02 in metastatic gastric cancer patients whose tumors can't be surgically removed and who have gotten worse on trastuzumab-containing regimens. In the DESTINY-Gastric03, advanced or metastatic HER2-positive gastric cancer patients will receive either trastuzumab deruxtecan alone, in combination with chemotherapy, in combination with durvalumab, or in combination with chemo and durvalumab. Last year, an interim analysis within DESTINY-Lung01 showed that trastuzumab deruxtecan shrank tumors in 26 out of 42 patients with HER2-mutated, metastatic non-small cell lung cancer.