“Practice-Changing” Results Seen With Targeted Therapy in HER2-Low Metastatic Breast Cancer

Results of the DESTINY-Breast04 study, presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, demonstrated significant survival benefit with trastuzumab deruxtecan versus standard of care chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer.

About half of patients (55%) with HER2-negative metastatic breast cancer express low levels of HER2 and experience poor outcomes in later lines of therapy. The randomized, multicenter, open-label, phase 3 study compared the efficacy of trastuzumab versus physician’s choice of treatment in this patient population.

As of January 11, 2022 (data cutoff), 557 patients with centrally confirmed HER2-low metastatic breast cancer were randomized 2:1 to receive trastuzumab 5.4 mg/kg (n=373) or physician’s choice of capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel (n=184).

Patients were followed for a median of 18.4 months (95% CI, 17.9-19.1), and most patients in both treatment cohorts (88.7% and 88.6%, respectively) had hormone receptor (HR)-positive disease.

Median treatment duration was 8.2 months (range, 0.2-33.3 months) with trastuzumab and 3.5 months (range, 0.3-17.6 months) with physician’s choice. Patients receiving trastuzumab had a statistically significant and clinically meaningful benefit in progression-free survival (PFS; primary endpoint) and overall survival (OS; secondary endpoint) compared with physician’s choice, regardless of HR status.

Among all patients in both cohorts, median PFS was 9.9 months (95% CI, 9.0-11.3) in the trastuzumab group versus 5.1 months (95% CI, 4.2-6.8) in the physician’s choice cohort (hazard ratio [HR], 0.50; P<.0001). Median OS in the full cohort was 23.4 months (95% CI, 20.0-24.8) versus 16.8 months (95% CI, 14.5-20.0), respectively (HR, 0.64; P=.001).

Among patients with HR-positive disease, median PFS nearly doubled in patients receiving trastuzumab versus physician’s choice: 10.1 months (95% CI, 9.5-11.5) versus 5.4 months (95% CI, 4.4-7.1; HR, 0.51; P<.0001). Median OS was 23.9 months (95% CI, 20.8-24.8) versus 17.5 months (95% CI, 15.2-22.4), respectively, in this cohort (HR, 0.64; P=.0028).

More than half of patients in both cohorts (52.6% treated with trastuzumab and 67.4% treated with physician’s choice) experienced grade ≥3 treatment-emergent adverse events. In the trastuzumab cohort, 45 patients (12.1%) had independently adjudicated drug-related interstitial lung disease/pneumonitis compared with just 1 patient (0.6%) in the physician’s choice cohort.

“[Trastuzumab] is the first HER2-targeted therapy to demonstrate statistically significant and clinically meaningful improvement in PFS and OS versus [physician’s choice],” said Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, during her presentation at ASCO. “These results establish HER2-low metastatic breast cancer as a targetable patient population, with [trastuzumab] as a new standard of care. We anticipate these results to be practice changing.”

Reference

Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan (T-DXd) versus treatment of physician’s choice (TPC) in patients (pts) with HER2-low unresectable and/or metastatic breast cancer (mBC): Results of DESTINY-Breast04, a randomized, phase 3 study. Abstract #LBA3. Presented at the 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.