At ASCO, Enhertu cements growing role in stomach cancer care

Yahoo

31-05-2025

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AstraZeneca and Daiichi Sankyo's targeted cancer medicine Enhertu helped participants in a late-stage clinical trial with a type of advanced gastric cancer live longer than those who received a commonly prescribed, two-drug regimen involving chemotherapy.
The finding, detailed Saturday at the American Society of Clinical Oncology's annual meeting, gives physicians a clearer choice for when patients' disease progresses after initial treatment.
Data from the trial should also shore up AstraZeneca and Daiichi's market position. Enhertu already won Food and Drug Administration approval for gastric cancer that's positive for a protein called HER2 following first-line treatment with Herceptin, an older HER2-targeting medicine.
A so-called antibody-drug conjugate, Enhertu combines the active agent in Herceptin with a chemotherapy toxin, delivering a more potent drug dose directly to HER2-expressing tumor cells than can be administered otherwise. It is one of six blockbuster cancer drugs sold by AstraZeneca and the fastest growing one, with more than $3 billion in 2024 revenue.
Cyramza, an Eli Lilly drug, is FDA-approved for gastric cancer that progresses following chemo. Small trials have suggested that, with Herceptin and chemo or just chemo, Cyramza can improve response rates and survival in people whose disease progressed on Herceptin. It is part of the standard second-line regimen Enhertu was tested against.
In AstraZeneca and Daiichi's trial, called Destiny-Gastric04, investigators randomized nearly 500 people with HER2-positive cancer who had progressed on Herceptin to receive either Enhertu or Cyramza plus a chemotherapy drug called paclitaxel. The trial measured overall survival as its main goal, with progression-free survival and response rates secondary endpoints.
Results showed that Enhertu reduced the risk of death by 30%, extending median survival by 3.3 months to reach 14.7 months, compared to 11.4 months for the Cyramza-chemo combination. The antibody-drug conjugate also reduced the risk of progression by 26%, delaying relapse or death by 1.1 months when compared to Cyramza and chemo.
Among Enhertu-treated patients, 44% had their tumors shrink or disappear, significantly more than the 29% of people given Cyramza and chemo.
'This study is practice-validating in the U.S., given [Enhertu's] existing inclusion in guidelines and current use in the second-line setting,' Pamela Kunz, a Yale University specialist in gastrointestinal cancer, said in a press conference ahead of the ASCO meeting. 'It will be practice-changing in many countries outside of the U.S., and will really position [Enhertu] as a preferred second-line treatment.'
The trial's findings only apply to HER2-positive patients, which account for as much as one-sixth of the roughly 30,000 new cases of stomach cancer each year.
Nearly all trial participants experienced side effects from treatment, although a slightly higher 93% of people who received Enhertu reported side effects compared with 91% on Cyramza. Similar numbers, around half in each group, had side effects judged to be severe or worse.
Nearly 14% given Enhertu experienced inflammation or scarring of lung tissue, a known side effect of the drug that previously prompted the FDA to put a 'black box' warning on its label.
Kunz said the incidence of lung damage should prompt doctors to 'take note' and 'think about patient selection and consider patient comorbidities' before prescribing Enhertu.
With Enhertu's place in the second-line setting now established, AstraZeneca and Daiichi are working to expand its use further by testing it in newly diagnosed people with inoperable HER2-positive tumors. The Destiny-Gastric05 trial is studying it in combination with Merck & Co.'s immunotherapy Keytruda and chemo head-to-head against the FDA-approved regimen of Herceptin, Keytruda and chemo. Results may not be available for three years, however.