News
Article
Neoadjuvant Trastuzumab Deruxtecan Improves Pathologic Complete Response in Patients With HER2+ Early Breast Cancer
Author(s):
Key Takeaways
- T-DXd followed by THP significantly improved pCR rates in high-risk, locally advanced HER2+ early-stage breast cancer compared to standard care.
- The DESTINY-Breast11 trial demonstrated T-DXd's favorable safety profile and potential to challenge current treatment standards.
Trastuzumab deruxtecan was safe and efficacious prior to treatment with paclitaxel, trastuzumab, and pertuzumab.
Trastuzumab deruxtecan (T-DXd, Enhertu; AstraZeneca) followed by paclitaxel (Taxol; Bristol Myers Squibb), trastuzumab (Herceptin; Genentech), and pertuzumab (Perjeta; Genentech; THP) yielded a clinically meaningful improvement in pathologic complete response (pCR) rate compared with standard of care (dose-dense doxorubicin and cyclophosphamide followed by THP [ddAC-THP]) in the neoadjuvant setting in patients with high-risk, locally advanced human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer (eBC). The data were observed in the phase 3 DESTINY-Breast11 trial (NCT05113251).1
3D rendering of antibody drug conjugates | Image Credit: © Love Employee - stock.adobe.com
About 20% of all BC diagnoses are HER2+ BC, which is one of the most prevalent HER2 mutations. Because of its aggressiveness, rapid development, and greater fatality rates than other BC subtypes, HER2+ BC is difficult to treat. These patients have historically had very poor prognoses, but the development of new drugs has dramatically improved these results, raising survival rates to almost 90%.2
“There are still many patients with early-stage breast cancer who do not achieve a pathologic complete response with treatment in the neoadjuvant setting, increasing the risk of disease recurrence,” Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, said. “These topline results from DESTINY-Breast11 demonstrate that [T-DXd] followed by THP could offer patients with [HER2+ BC] a promising new treatment approach prior to surgery, setting more patients on a path towards a potential cure.”3
T-DXd is an antibody drug conjugate consisting of a HER2 monoclonal antibody attached to multiple topoisomerase I inhibitor payloads, allowing the agent to selectively bind and target HER2+ mutations. Its efficacy has been previously reported across various DESTINY-Breast clinical trials, leading to the drug’s FDA approval across multiple BC indications.2
The DESTINY-Breast11 trial is a global, multicenter, randomized, open-label, phase 3 study evaluating the safety and efficacy of neoadjuvant T-DXd at a dosage of 5.4 mg per kg monotherapy or T-DXd followed by THP compared with the standard of care regimen in patients with high-risk (lymph node positive [N1-3] or primary tumor stage T3-4), locally advanced, or inflammatory HER2+ eBC. The primary end point of the study is pCR, which is associated with improved long-term treatment outcomes. Secondary end points include event-free survival, invasive disease-free survival, overall survival, and safety.3
The trial randomized 927 patients 1:1:1 to receive either 8 cycles of T-DXd monotherapy; 4 cycles of T-DXd followed by 4 cycles of THP; or 4 cycles of ddAC followed by 4 cycles of THP. The data showed that T-DXd prior to THP had an improved safety profile compared with ddAC-THP, which aligned with the known safety profiles of each agent. Notably, neoadjuvant T-DXd followed by ddAC-THP yielded statistically significant improvements in pCR.3
“The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of [T-DXd] to challenge the current standard of care in [HER2+ eBC],” Susan Galbraith, MBBChir, PhD, executive vice president, Oncology Hematology R&D, AstraZeneca, said in a news release. “[T-DXd] is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible.”3
