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For HER2-mutant NSCLC, FDA grants accelerated approval to Enhertu, approves companion diagnostics

September 2022—The Food and Drug Administration on Aug. 11 granted accelerated approval to Enhertu for adult patients with unresectable or metastatic non-small cell lung cancer whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. Enhertu (AstraZeneca and Daiichi Sankyo) is the first drug approved for HER2-mutant NSCLC.

The FDA also approved Thermo Fisher Scientific’s Oncomine Dx Target Test and Guardant Health’s Guardant360 CDx liquid biopsy test as companion diagnostics to identify patients whose tumors have HER2 (ERBB2) activating mutations in NSCLC and may benefit from treatment with Enhertu (trastuzumab deruxtecan). If no mutation is detected in a plasma specimen, the FDA said in its release, the tumor tissue should be tested.

Efficacy for accelerated approval was based on DESTINY-Lung02, a multicenter, multi-cohort, randomized, blinded, dose-optimization trial. The confirmed objective response rate was 58 percent (95 percent CI: 43, 71), and the median duration of response was 8.7 months (95 percent CI: 7.1, not estimable).

FDA approves Enhertu for patients with HER2-low metastatic breast cancer

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the U.S. for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate. The FDA’s approval was based on results from the DESTINY-Breast04 phase three trial. In the trial, Enhertu reduced the risk of disease progression or death by 50 percent versus the physician’s choice of chemotherapy in patients with HER2-low metastatic breast cancer with hormone-receptor-positive disease or HR-negative disease (median progression-free survival 9.9 versus 5.1 months; hazard ratio 0.50; 95 percent CI: 0.40–0.63). A median overall survival of 23.4 months was seen in patients treated with Enhertu versus 16.8 months in those treated with chemotherapy.

The expanded approval for Enhertu in the U.S., following its previous approval in second-line HER2-positive metastatic breast cancer, enables its use across a spectrum of HER2-expressing breast cancer, including patients with HER2-low disease.

The DESTINY-Breast04 phase three trial results were presented at this year’s American Society of Clinical Oncology annual meeting and published in July (Modi S, et al. N Engl J Med. 2022;387[1]:9–20).

AMP publishes TPMT and NUDT15 report

The Association for Molecular Pathology on Aug. 25 published consensus recommendations to aid in the design and validation of clinical TPMT and NUDT15 genotyping assays.