Trastuzumab Deruxtecan Improves PFS, OS in T-DM1–Pretreated HER2+ Metastatic Breast Cancer

Fam-trastuzumab deruxtecan-nxki (Enhertu) led to a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) vs treatment with physician’s choice in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with ado-trastuzumab emtansine (T-DM1; Kadcyla), meeting the primary and secondary end points of the phase 3 DESTINY-Breast02 study (NCT03523585).¹

Additionally, the safety profile of trastuzumab deruxtecan was consistent with prior phase 3 clinical trials with no new safety concerns identified. Notably, the rates and severity of interstitial lung disease (ILD) were consistent with those reported in prior trials with trastuzumab deruxtecan in the metastatic setting, with a low rate of grade 5 ILD as determined by an independent adjudication committee.

The trial evaluated a similar pretreated patient population as the single-arm, phase 2 DESTINY-Breast01 trial (NCT03248492), which served as the basis for the initial FDA accelerated approval and conditional approval in the European Union of the agent in patients with unresectable or metastatic HER2-positive breast cancer who have previously received 2 or more anti-HER2–based regimens.

The results from DESTINY-Breast02 will be presented at an upcoming medical meeting.

“The topline results from DESTINY-Breast02 confirm the robust PFS seen in previous trials of trastuzumab deruxtecan and enrich our clinical understanding of the benefit this therapy may offer patients with HER2-positive metastatic breast cancer,” Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, stated in a press release. “As this is the confirmatory trial for our current breast cancer indication in Europe and several other countries, we look forward to sharing these findings with regulatory authorities to add to the body of data for trastuzumab deruxtecan for the treatment of HER2-positive metastatic breast cancer.”

DESTINY-Breast02 is a global, randomized, open-label, pivotal phase 3 trial evaluating the efficacy and safety of trastuzumab deruxtecan at a dose of 5.4 mg/kg vs physician’s choice of treatment consisting of trastuzumab (Herceptin) plus capecitabine (Xeloda) or lapatinib (Tykerb) plus capecitabine in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with T-DM1.²

Patients were randomized 2:1 to receive trastuzumab deruxtecan or physician’s choice of treatment.

The primary end point of the study is PFS based on blinded independent central review (BICR). The key secondary end point is OS. Other secondary end points include objective response rate based on BICR and investigator assessment, duration of response based on BICR, PFS based on investigator assessment, and safety.

“The DESTINY-Breast02 trial results in this patient population with advanced disease confirm the efficacy and safety profile seen in DESTINY-Breast01 and are consistent with the results seen across our broader 2 clinical program in HER2-positive metastatic breast cancer,” Susan Galbraith, MBBChir, PhD, executive vice president of Oncology R&D at AstraZeneca, said. “These data further strengthen our confidence in trastuzumab deruxtecan and reinforce its potential to transform patient outcomes across multiple treatment settings.”

References

1. ENHERTU® significantly delayed disease progression in DESTINYBreast02 phase 3 trial versus physician’s choice of treatment in patients with HER2 positive metastatic breast cancer. News release. Daiichi Sankyo. August 15, 2022. Accessed August 15, 2022. https://bit.ly/3pqJMSx
2. DS-8201a in pre-treated HER2 breast cancer that cannot be surgically removed or has spread [DESTINY-Breast02]. ClinicalTrials.gov. Updated August 12, 2022. Accessed August 15, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03523585