News|Articles|August 17, 2026

Enhertu Delayed Cancer Growth as a First Treatment for HER2-Mutant Lung Cancer

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Key Takeaways

Enhertu outperformed platinum–pemetrexed plus pembrolizumab on the primary endpoint of PFS in first-line HER2-mutant non-squamous NSCLC, establishing a phase 3 benchmark versus global standard care.
Trial design included 454 patients randomized 1:1 to trastuzumab deruxtecan 5.4 mg/kg or standard therapy, stratified by smoking history and presence of brain metastases.
Blinded independent central review adjudicated PFS, while secondary endpoints include overall survival, investigator-assessed PFS, objective response rate, duration of response, pharmacokinetics, and safety.
Safety findings aligned with the established trastuzumab deruxtecan profile, with no new safety concerns; OS follow-up and full efficacy data will be presented and submitted to regulators.
HER2 mutations occur in ~2%–4% of non-squamous NSCLC, often in younger women and never-smokers, underscoring the need for effective targeted first-line options.

The phase 3 DESTINY-Lung04 trial met its main goal of keeping cancer from growing longer than chemotherapy plus immunotherapy did.

Enhertu (trastuzumab deruxtecan) kept cancer from growing longer than the current standard first treatment did in patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC), according to top-line findings from the global phase 3 DESTINY-Lung04 trial released by AstraZeneca and Daiichi Sankyo. Enhertu is an antibody-drug conjugate, a treatment that carries a cancer-killing drug directly to cells that carry the HER2 protein.

What did the phase 3 DESTINY-Lung04 trial find in HER2-mutant non-small cell lung cancer?

The trial met its primary end point (its main measure of success) of progression-free survival. Progression-free survival is the length of time patients live without their cancer growing or spreading. The improvement was described as statistically significant, meaning the difference between the two treatment groups was unlikely to have come about by chance, and as clinically meaningful for patients.

Patients who received Enhertu were compared with patients who received the global standard of care for a first treatment, which combines platinum-pemetrexed doublet chemotherapy with the immunotherapy drug Keytruda (pembrolizumab).

"Our oncology pipeline continues to advance with DESTINY-Lung04 becoming the first phase 3 trial to demonstrate a progression-free survival benefit versus the global standard of care in this first-line setting, supporting the potential for Enhertu to move earlier in the treatment of HER2-mutant non-small cell lung cancer," said Susan Galbraith, executive vice president of oncology hematology research and development at AstraZeneca, in the news release. Galbraith added that HER2-mutant lung cancer often affects younger patients and has had limited targeted options as a first treatment.

Enhertu is already approved for patients with metastatic NSCLC whose tumors carry activating HER2 mutations and who have received a prior treatment.

"The positive results seen in DESTINY-Lung04 show that treatment with Enhertu in the first-line setting delays disease progression compared to the global standard of care, highlighting its potential to improve outcomes for patients earlier in the treatment of metastatic disease," noted John Tsai, global head of research and development at Daiichi Sankyo, in the release.

No effect sizes were included in the announcement, so how much longer Enhertu held cancer in check is not yet public.

What did the DESTINY-Lung04 trial measure in patients with HER2-mutant NSCLC?

DESTINY-Lung04 is a global, randomized, open-label phase 3 trial, meaning patients were assigned to treatment by chance and both patients and doctors knew which treatment was given. The trial enrolled 454 patients across sites in Asia, Europe and North America, all of whom had non-squamous NSCLC with a HER2 mutation.

Patients were assigned in equal numbers to Enhertu at 5.4 mg/kg or to standard of care. Assignment took into account smoking history and whether a patient had brain metastases, which are tumors that have spread to the brain.

Progression-free survival was assessed by blinded independent central review, meaning radiologists outside the treating centers evaluated the scans without knowing which treatment a patient received. Secondary end points include overall survival, which is how long patients live after starting treatment, along with progression-free survival as judged by the treating doctors, how many patients responded to treatment, how long those responses lasted, how the drug moves through the body and safety.

HER2 mutations occur in 2% to 4% of patients with non-squamous NSCLC and are seen predominantly in younger women and people with no smoking history, according to research cited in the release. Research has also linked HER2-positive breast cancer with a higher risk of cancer spreading to the brain.

What side effects were reported with Enhertu in DESTINY-Lung04?

The safety profile of Enhertu in DESTINY-Lung04 was generally consistent with what has been seen with the drug before, and no new safety concerns were identified, according to the release.

The trial is continuing as planned to evaluate overall survival and the remaining secondary end points. Full results from DESTINY-Lung04 will be presented at an upcoming medical meeting and shared with regulatory agencies.

References

"Enhertu demonstrated statistically significant and clinically meaningful improvement in progression-free survival as 1st-line treatment of patients with HER2-mutant advanced non-small cell lung cancer in DESTINY-Lung04 phase 3 trial." News release. AstraZeneca. Aug. 17, 2026.

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