News from the FDA/CDC

FDA approves Enhertu (trastuzumab deruxtecan) for HER2 lung cancer


Patients with lung cancer now have another treatment option: If their tumors are found to carry HER2 mutations, they can now be treated with trastuzumab deruxtecan (Enhertu), a drug that specifically targets that defect.

This product is already approved for used in HER2-positive breast cancer and gastric cancer. Now it has become the first product approved by the U.S. Food and Drug Administration for use in HER2-positive lung cancer.

The FDA also approved companion diagnostic tests to detect HER2 mutations: Life Technologies Corporation’s Oncomine Dx Target Test for use in lung tissue and Guardant Health’s Guardant360 CDx for use on plasma samples. The agency notes that if no mutation is detected in a plasma specimen, the tumor tissue should be tested.

Specifically, the new indication is used in patients with unresectable or metastatic non–small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have already received a prior systemic therapy.

About 3% of nonsquamous NSCLC tumors carry mutations in the HER2 gene, and they are associated with female sex, never-smokers, and a poor prognosis.

“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,” said Dave Fredrickson, executive vice-president of the oncology business unit at AstraZeneca.

The new approval “provides these patients with the opportunity to benefit from a targeted therapy and 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,” he commented in a company press release.

This is an accelerated approval, based on overall response rate data from the DESTINY-Lung02 phase 2 trial, the company noted. An interim efficacy analysis in a prespecified patient cohort showed that trastuzumab deruxtecan (at 5.4 mg/kg) demonstrated a confirmed overall response rate of 57.7% (n = 52; 95% confidence interval, 43.2%-71.3%) in patients with HER2-mutant unresectable or metastatic nonsquamous NSCLC who had received one prior systemic therapy as assessed by blinded independent central review. Complete responses were seen in 1.9% of patients (n = 1) and partial responses in 55.8% of patients (n = 29), with a median duration of response of 8.7 months (95% CI, 7.1-NE).

The FDA noted that for the 52 patients in the primary efficacy population of the DESTINY-Lung02 trial, the median age was 58 years (range, 30-78 years); 69% were female; and 79% were Asian, 12% were White, and 10% were of other races.

Clinical data welcomed by experts

Clinical data are already available from the DESTINY-Lung 01 trial, and the results were welcomed enthusiastically by experts when they were published in the New England Journal of Medicine earlier this year.

“These results establish the new standard of care for patients with NSCLC harboring HER2 mutations,” Antonio Passaro, MD, PhD, from the European Institute of Oncology IRCCS, Milan, and Solange Peters, MD, PhD, from Lausanne (Switzerland) University Hospital, wrote in an accompanying editorial.

This trial involved 91 patients, all treated with trastuzumab deruxtecan (at 6.4 mg/kg of body weight every 3 weeks). The median duration of treatment was 6.9 months, and the median follow-up was 13.1 months.

The results showed a 55% centrally confirmed objective response, and median duration of response was 9.3 months.

In addition, the investigators reported a median progression-free survival of 8.2 months and a median overall survival of almost 18 months, both of which they described as “encouraging” in this patient population.

However, the results also highlighted a problem with the drug in this patient population. Notably, 26% of patients experienced interstitial lung disease, which resulted in death in two patients. The drug was also withdrawn in 16 patients and interrupted in 8 patients because of this adverse event.

Editorialists Dr. Passaro and Dr. Peters described this finding as “a concern” and note that “the incidence of interstitial lung disease is significantly higher among patients with lung cancer than among those with breast or gastric cancers, which may indicate a role of smoking-related damage.”

They also highlighted the need for an “investigation of the clinical efficacy of a reduced dose of trastuzumab deruxtecan,” and so the dose was reduced for the DESTINY-Lung02 trial.

A version of this article first appeared on

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