In conversation with SurvivorNet, Dr. Harold Burstein–world renown clinical researcher and breast oncologist–offered his perspective on Enhertu (trastuzumab deruxtecan) and the global phase 3 DESTINY-Breast11 trial, emphasizing that while the drug offers promise, questions remain about how applicable the study design is to current U.S. practice.
Trial Design and Results
- DESTINY-Breast11 evaluated a preoperative strategy of trastuzumab deruxtecan followed by THP (taxane, trastuzumab, pertuzumab) versus a more traditional regimen of dose-dense AC (doxorubicin/cyclophosphamide) followed by THP in patients with HER2-positive early-stage breast cancer.
- Enhertu (trastuzumab deruxtecan) followed by THP significantly increased the rate of pathologic complete response — about 67% versus ~56% with standard ddAC-THP — in patients with high-risk HER2-positive early-stage breast cancer in the neoadjuvant setting
Dr. Burstein’s Takeaways Summarized
- Comparator choice matters
- Global trials shape drug development — and regulatory decisions
- Clinicians must scrutinize the fine print
Interpreting DESTINY-Breast11 in U.S. Practice
Although the study demonstrated a higher pathologic complete response (pCR) rate with the T-DXd–based approach—an encouraging signal suggesting deeper tumor eradication before surgery–Dr. Burstein cautions that context matters. While anthracycline-based regimens remain common globally, U.S. practice has largely shifted away from AC in HER2-positive disease. Most American patients instead receive TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab), a regimen that in some prior studies has shown higher response rates than AC-THP.
For Dr. Burstein, that raises the question of whether DESTINY-Breast11 used the most relevant comparator for U.S. patients.
Is This the Right Benchmark?
“You have to wonder if it’s really the optimal comparison and then they would like to show data for recurrence-free survival, but at least 40 plus percent of the patients who had residual cancer did not receive the current standard of care of trastuzumab,” Dr. Burstein says. “If you want to make claims about overall survival or even event-free survival and you don’t give people a drug, which has been the standard of care in the United States since 2019, there’s an argument here that you are conforming to what local standards of care might be for studies done in Asia, south Asia, middle East, other parts of Latin America around the world, but that’s not the outcomes that American patients and Western European patients would anticipate.”
“These things have big consequences because of course in many parts of the world there’s pricing and approval for drugs,” Dr. Burstein says, referring to the regulatory, pricing, and approval implications tied to event-free or overall survival results. “Showing an event-free survival or overall survival benefit matters from a regulatory and pricing point of view — and of course for understanding how important the drug really is to the natural history.”
He emphasizes that this dynamic is not unique to breast cancer. Across major international meetings such as ESMO, most pivotal phase 3 trials now enroll patients worldwide. While that model reflects the future of drug development, he says, clinicians in highly resourced countries must look carefully at trial design — including the control regimen and use of modern post-surgical standards of care — to determine how closely the results reflect the experience their own patients would expect.
For Burstein, the takeaway is clear: global trials drive drug development, but clinicians must scrutinize design details to understand what the results truly mean for their patients.
