AstraZeneca and Daiichi Sankyo reported that their cancer drug Enhertu (fam-trastuzumab deruxtecan-nxki) demonstrated a median progression-free survival (PFS) of 14.3 months as a first-line treatment in patients with HER2-mutant advanced non-small cell lung cancer (NSCLC), compared with 8.3 months for pembrolizumab plus chemotherapy, according to results from the DESTINY-Lung04 Phase III trial.

The trial's primary endpoint showed Enhertu reduced the risk of disease progression or death by 37% versus the standard-of-care combination (hazard ratio 0.63; 95% CI 0.50-0.79; p<0.0001). The objective response rate with Enhertu was 70.0%, compared with 44.5% for pembrolizumab plus chemotherapy. Median duration of response was 13.4 months with Enhertu versus 9.7 months with the comparator arm.

Overall survival data were 46.9% mature at the time of analysis, and no formal hypothesis testing was performed. Median OS was 29.3 months in the Enhertu arm versus 33.1 months in the pembrolizumab plus chemotherapy arm, though the companies noted that imbalanced subsequent therapy patterns between arms — including greater use of HER2-directed therapies in the comparator arm — may limit interpretation of that result.

Grade 3 or higher treatment-related adverse events were comparable between the two arms at 34.1% and 33.6%, respectively, despite longer treatment exposure in the Enhertu arm. Interstitial lung disease or pneumonitis occurred in 20.8% of patients treated with Enhertu, including four Grade 5 events. The safety profile was described as consistent with Enhertu's known profile.

The results were presented at the IASLC 2026 World Conference on Lung Cancer in Seoul, South Korea. The trial enrolled 454 patients across sites in Asia, Europe, and North America.

Enhertu is currently approved in more than 80 countries for previously treated HER2-mutant NSCLC. The companies said they plan to discuss the DESTINY-Lung04 data with regulatory authorities. The information is based on a press release issued by AstraZeneca.