Trastuzumab Deruxtecan Significantly Improved PFS Over TDM-1 for HER2+ Metastatic Breast Cancer

Article

Results from the DESTINY-Breast03 trial identified that trastuzumab deruxtecan improved survival in patients with HER2-positive metastatic breast cancer compared with trastuzumab emtansine.

Trastuzumab deruxtecan (Enhertu) demonstrated superior progression-free survival (PFS) outcomes over trastuzumab emtansine (T-DM1; Kadcyla) in patients with HER2-positive metastatic breast cancer, according to a press release on the phase 3 DESTINY-Breast03 trial (NCT03529110) by drug developer AstraZeneca.1

The study’s planned interim analysis identified a statistically significant and clinically meaningful improvement in the primary end point of PFS as assessed by an Independent Data Monitoring Committee (IDMC) for patients with HER2-positive, unresectable and/or metastatic breast cancer who received prior treatment with trastuzumab (Herceptin) and a taxane.

“There is a continued need for new options and better outcomes for patients with HER2-positive metastatic breast cancer who often experience disease progression after initial treatment with available standards of care,” Susan Galbraith, MB, BChir, executive vice president of Oncology R&D at AstraZeneca, explained in a press release. “These transformative progression-free survival results demonstrate the superiority of Enhertu compared to T-DM1, and the encouraging safety data may open future opportunities to bring this benefit to patients in earlier treatment settings.”

Approximately 500 patients were enrolled in the DESTINY-Breast03 trial, who were randomized to either the experimental trastuzumab deruxtecan arm or the comparator T-DM1 arm. The primary end point was PFS assessed by IDMC, with secondary end points including overall survival (OS), objective response rate (ORR), duration of response, and PFS based on investigator assessment.

Eligible patients needed to be 18 years or older with pathologically documented breast cancer that is unresectable or metastatic, along with confirmed HER2 expression. Previous treatment with trastuzumab and taxane in the advanced or metastatic setting was also required.

While patients treated with trastuzumab deruxtecan trended toward OS improvement, the data were immature. Furthermore, the safety profile was consistent with previously reported data regarding trastuzumab deruxtecan, with no new safety signals or grade 4/5 treatment-related interstitial lung disease events observed.

“DESTINY-Breast03 is the first global Phase III head-to-head trial of Enhertu against an active control and supports the potential of this medicine to become the new standard of care for patients with HER2-positive metastatic breast cancer following initial treatment with trastuzumab and a taxane,” Ken Takeshita, global head of research and development at Daiichi Sankyo, said in a press release. “We believe this highly sophisticated and specifically engineered ADC is fulfilling its promise to reshape the treatment of HER2-positive metastatic breast cancer, with the goal to move into earlier lines of treatment for HER2-positive breast cancer and many other HER2-expressing tumour types across our broad clinical trial programme.”

Both AstraZeneca and Daiichi Sankyo expect that the data will be presented and shared with health authorities at an upcoming medical conference.

Previous findings with the drug were identified through the phase 2 DESTINY-Breast01 trial (NCT03248492) and led to the FDA approval of trastuzumab deruxtecan in December 2019 for adult patients with unresectable or metastatic HER2-positive breast cancer who underwent treatment with 2 or more prior anti-HER2-based regimens.2

Findings from the trial indicated that those who were treated with the recommended dose of trastuzumab deruxtecan experienced a response rate of 60.9% of patients (95% CI, 53.4%-68.0%).3 The median duration of response was reported at 14.8 months (95% CI, 13.8-16.9), with a median duration of PFS of 16.4 months (95% CI, 12.7–not reached).

References

  1. Enhertu significantly improved progression-free survival in DESTINY-Breast03 head-to-head trial vs. trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer. News release. AstraZeneca. Published August 9, 2021. Accessed August 9, 2021. https://tinyurl.com/m5u78
  2. FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies. News release. FDA. December 20, 2019. Accessed August 9, 2021. https://bit.ly/3lOfBV6
  3. Modi S, Saura C, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382(7):610-621. doi:10.1056/NEJMoa1914510
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