FDA Accelerated Approval Expands Enhertu Indication to NSCLC

 AstraZeneca/Daiichi drug becomes first specifically approved for HER2 mutant NSCLC.

Enhertu (trastuzumab deruxtecan) became the darling of this summer's 2022 ASCO Annual meeting when its remarkable study results revealed the possibility of a new treatment option for patients with HER2-low breast cancer.

Investigator and presenter Shanu Modi, MD, of the Memorial Sloan Kettering Cancer Center, earned a standing ovation after her ASCO presentation on the phase 3 DESTINY-Breast04 trial.

Enhertu is the first HER2-directed therapy to demonstrate a survival benefit in this population, and these results hold the promise of changing the standard of care for patients with HER2-low breast cancer.

Continuing its winning streak this month, the antibody drug conjugate received accelerated approval to treat adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC), making it the first drug specifically approved for HER2 mutant NSCLC.

"The availability of Enhertu as the first HER2 targeted treatment option for HER2 mutant non-small cell lung cancer is great news for patients," Upal Basu Roy, PhD, MPH, executive director of research at LUNGevity, says in a prepared statement. "We are thrilled to see a novel treatment option available that targets this group of rare mutations in lung cancer. This approval is a great reminder that access to high-quality biomarker testing will be critical to ensuring that patients whose tumors have HER2 mutations have access to these new therapies."

The approval was based on results from the DESTINY-Lung02 phase 2 trial. Patients with HER2 mutant unresectable or metastatic non-squamous NSCLC responded to the drug with a 57.7% objective response rate. In the trial, investigators evaluated the safety and efficacy of two doses of trastuzumab deruxtecan-nxki (5.4 mg/kg and 6.4 mg/kg) in 152 patients with HER2 mutant metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy (including a platinum-based chemotherapy). 

"HER2-mutant non-small cell lung cancer is an aggressive form of disease which commonly affects young patients who have faced limited treatment options and a poor prognosis to date," says Dave Fredrickson, executive vice president, oncology business unit at AstraZeneca, in the press release. This highlights the importance of testing for predictive markers, including HER2 in lung cancer, at the time of diagnosis to ensure patients receive the most appropriate treatment for their specific disease.

To that end, the FDA also cleared a companion diagnostic test, the Oncomine Dx Target Test by Thermo Fisher Scientific, to identify NCSLC patients who may be candidates for trastuzumab deruxtecan-nxki. The diagnostic test is designed to simultaneously evaluate 23 genes associated with NSCLC.

This marks the third indication for Enhertu to receive FDA approval. In May, Enhertu was approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer and again in early August as the first HER2-directed therapy for patients with HER2-low metastatic breast cancer.

Daiichi and AstraZeneca have been collaborating since 2019 to jointly develop and commercialize trastuzumab deruxtecan and according to the companies, "a comprehensive development program is underway across multiple HER2 targetable cancers, including breast, gastric, lung and colorectal cancers."

There's more to come from this exciting breakthrough drug.