In updated results from the pivotal DESTINY-Breast01 trial, trastuzumab deruxtecan-nxki (T-DXd) demonstrated high rates of durable responses consistent with prior results, with encouraging progression-free survival and overall survival in patients with HER2-positive metastatic breast cancer. These updates were presented by Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, at PER’s Miami Breast Cancer Conference, held virtually this year.
Shanu Modi, MD
“With 9.4 months of additional follow-up, T-DXd continued to demonstrate clinically meaningful and durable efficacy, with an unprecedented median duration of response of 20.8 months,” said Dr. Modi. “Treatment resulted in a robust survival outcome, with an 18-month landmark overall survival of 74%.”
DESTINY-Breast01 is an open-label, international, multicenter, phase II study of trastuzumab deruxtecan in patients with HER2-positive metastatic breast cancer. The study results supported regulatory approval in the United States, the European Union, and Japan. Dr. Modi presented safety and efficacy results after longer follow-up.
Study Details
In the trial,184 patients with metastatic breast cancer that progressed on or after treatment with trastuzumab emtansine received T-DXd 5.4 mg/kg. The primary endpoint was confirmed objective response rate by independent central review.
Dr. Modi presented results from an updated data cutoff of June 2020, which was based on a median follow-up of 20.5 months; the prior analysis was done after 11.1 months of follow-up.
The confirmed objective response rate was 61.4%, and the median duration of response was 20.8 months. At the earlier data cutoff, confirmed response rate was 60.9%, and median duration of response was 14.8 months.
At the August 2019 data cutoff, 79 of 184 patients remained on treatment (42.9%); at the June 2020 data cutoff, 37 of 184 patients remained on treatment (20.1%).
Updated results showed a complete response rate of 6.5%, a partial response rate of 54.9%, and a stable disease rate of 35.9%; these rates at the earlier cutoff were 6.0%, 54.9%, and 36.4%, respectively.
With 9.4 months of additional follow-up, T-DXd continued to demonstrate clinically meaningful and durable efficacy, with an unprecedented median duration of response of 20.8 months. Treatment resulted in a robust survival outcome, with an 18-month landmark overall survival of 74%.— Shanu Modi, MD
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Median progression-free survival was 19.4 months at the updated cutoff; it was 16.4 months at the earlier cutoff. Median overall survival was 24.6 months in June 2020 vs not estimable in August 2019; 12-month overall survival estimates were 85% vs 86.2% and 18-month overall survival estimates were 74% vs not estimable.
The safety profile was consistent with previous results. After an additional 9 months of follow-up, three new cases of T-DXd–related interstitial lung disease were reported. The rate of discontinuation or interstitial lung disease did not notably increase with 9 months additional follow-up, the poster indicated.
The rate of grade ≥ 3 treatment-related adverse events was 61.4% at the later cutoff vs 57.1% at the earlier cutoff.
“In this analysis, the risk of adjudicated drug-related interstitial lung disease appears lower after approximately 12 months on treatment, suggesting that the risk of developing interstitial lung disease is not related to a cumulative dose of T-DXd,” Dr. Modi said. “Continued attention to pulmonary symptoms and careful monitoring is warranted.”
Disclosure: Dr. Modi has served in a consulting/speaking role for Genentech, Daiichi Sankyo, and AstraZeneca; has served in a consulting role for Seattle Genetics and Macrogenics; and has received research support from Genentech, Daiichi Sankyo, AstraZeneca, and Seattle Genetics.
