The primary end point of improved progression-free survival was met in the phase 3 DESTINY-Breast02 trial when patients with HER2-positive unresectable and/or metastatic breast cancer were given trastuzumab deruxtecan vs physician’s choice of therapy.
Treatment with trastuzumab deruxtecan (T-DXd; Enhertu) yielded a statistically significant and clinically meaningful improvement of progression-free survival (PFS) vs physician’s choice of chemotherapy in patients with HER2-positive unresectable and/or metastatic breast cancer who have previously been treated with trastuzumab emtansine (T-DM1; Kadcyla), according to a press release from AstraZeneca on the phase 3 DESTINY-Breast02 trial (NCT03523585).
The trial also met the secondary end point of overall survival. The updated results highlighted a similar safety profile as seen in phase 3 previous clinical trials, with incidence and grade of interstitial lung disease (ILD) remaining consistent with prior findings. Importantly, the occurrence of grade 5 ILD remained low in the trial, according to findings from an independent adjudication committee. Findings from the trial will be presented at an upcoming medical meeting.
“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 clinical program in HER2-positive metastatic breast cancer. These data further strengthen our confidence in [T-DXd] and reinforce its potential to transform patient outcomes across multiple treatment settings,” Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, said in the press release.
About 600 patients enrolled on the trial across Asia, Oceania, Europe, and North and South America. Patients were randomly assigned 2:1 and given either 5.4 mg/kg of T-DXd or physician’s choice of therapy. Additional secondary end points included objective response rate via blinded independent review (BICR), duration of response by BICR, PFS via investigator assessment, and safety.
Patients were eligible for the trial if they had pathologically documented breast cancer, documented radiologic progression, were HER2-positive with confirmation via central laboratory assessment or recent tumor tissue sample, and had adequate hematopoietic, renal, and hepatic functions.
Patients were excluded from the study if they had previously been enrolled in an antibody-drug conjugate study, had prior treatment with capecitabine (Xeloda), and had uncontrolled or significant cardiovascular disease. Patients also could not have a history of ILD or pneumonitis requiring steroids or suspected disease that cannot be ruled out by imaging, or have active nervous central system metastases.
T-DXd at 5.4 mg/kg has been FDA approved in other indications such as for those with unresectable or metastatic HER2-positive breast cancer who have received 1 or more prior anti-HER2 therapies in the metastatic, neoadjuvant, or adjuvant setting and who developed disease recurrence during or within 6 months of completing therapy, based on findings from the phase 3 DESTINY-Breast03 trial (NCT03529110). Additionally, based on findings from the phase 2 DESTINY-Breast01 trial (NCT03248492), T-DXd was approved by the FDA for those with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2 therapies. Additionally, the data from the phase 3 DESTINY-Breast04 trial (NCT03734029), which enrolled those with unresectable or metastatic HER2-low breast cancer with an immunohistochemistry chemistry score of 1+ or 2+ who had received prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy, led to another FDA approval.
“The top-line results from DESTINY-Breast02 confirm the robust [PFS] seen in previous trials of [T-DXd] and enrich our clinical understanding of the benefit this therapy may offer patients with HER2-positive metastatic breast cancer. 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 [T-DXd] for the treatment of HER2-positive metastatic breast cancer,” Ken Takeshita, global head of Research and Development at Daiichi Sankyo, concluded.
Enhertu significantly delayed disease progression in DESTINY-Breast02 Phase III trial Vs. physician’s choice of treatment in patients with HER2-positive metastatic breast cancer. News Release. AstraZeneca. August 15, 2022. Accessed August 15, 2022. https://bit.ly/3AmIMVS