Wilmington, Del. — AstraZeneca and Daiichi Sankyo said Enhertu demonstrated a statistically significant improvement in progression-free survival compared with pembrolizumab plus chemotherapy as a first-line treatment for patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer.
Results from the Phase 3 DESTINY-Lung04 trial showed median progression-free survival of 14.3 months with Enhertu compared with 8.3 months for pembrolizumab plus chemotherapy. Enhertu reduced the risk of disease progression or death by 37%, according to blinded independent central review.
The objective response rate was 70% with Enhertu compared with 44.5% with pembrolizumab plus chemotherapy. Median duration of response was 13.4 months and 9.7 months, respectively.
“HER2-mutant non-small cell lung cancer is an aggressive disease with limited responses to current 1st-line standard of care, and many patients experience disease progression within a year of starting treatment. With seventy percent of patients responding and a median progression-free survival of 14.3 months, trastuzumab deruxtecan has the potential to become an important new 1st-line treatment option for these patients,” said Julia Rotow, M.D., Assistant Professor of Medicine at Dana-Farber Cancer Institute and lead investigator of the trial.
AstraZeneca said the study was the first Phase 3 trial to demonstrate superior progression-free survival over the global first-line standard of care in patients with HER2-mutant advanced non-small cell lung cancer.
At the time of the analysis, overall survival data were 46.9% mature and no formal hypothesis testing had been performed. The companies said no overall survival benefit had been observed at that point, while differences in subsequent therapies between the treatment groups could affect interpretation of the results.
The safety profile of Enhertu was generally consistent with its known profile, with no new safety concerns identified. Grade 3 or higher treatment-related adverse events occurred in 34.1% of patients receiving Enhertu and 33.6% receiving pembrolizumab plus chemotherapy.
Interstitial lung disease or pneumonitis occurred in 20.8% of patients treated with Enhertu. Most cases were Grade 1 or 2, although five Grade 3, one Grade 4 and four Grade 5 events were reported.
Enhertu is a HER2-directed antibody-drug conjugate discovered by Daiichi Sankyo and jointly developed and commercialized by AstraZeneca and Daiichi Sankyo.
