Researchers presented striking phase III data at the ESMO Congress 2025, and the findings were summarized in Nature Reviews Clinical Oncology (2025). The DESTINY-Breast05 trial found that patients with residual HER2-positive breast cancer after standard neoadjuvant therapy experienced substantially better invasive disease-free survival at three years when treated with trastuzumab deruxtecan (T-DXd) as adjuvant therapy than with the current comparator, trastuzumab emtansine (T-DM1). Invasive disease-free survival was 92.4 percent with T-DXd versus 83.7 percent with T-DM1, corresponding to a hazard ratio of 0.47 (95 percent CI 0.34–0.66), indicating roughly a 53 percent reduction in the risk of invasive disease events during the follow-up period.

In a separate pivotal trial, KEYNOTE-905 tested perioperative therapy with enfortumab vedotin (EV) plus the immune checkpoint inhibitor pembrolizumab in patients with muscle-invasive bladder cancer who were not eligible for, or who declined, cisplatin-based chemotherapy. The combination significantly extended event-free survival compared with observation: the median duration was not reached in the treatment arm versus 15.7 months with observation, yielding a hazard ratio of 0.40 (95 percent CI 0.28–0.57). The not-yet-reached median suggests that a substantial proportion of treated patients remained free of disease progression or recurrence at the time of analysis.

Taken together, the trials represent meaningful clinical advances for two populations with high unmet needs. For patients with residual disease after neoadjuvant therapy, the magnitude of benefit with T-DXd could shift adjuvant practice and reduce recurrence rates. For muscle-invasive bladder cancer, the EV–pembrolizumab regimen offers a viable perioperative strategy for patients who cannot receive cisplatin, a group that includes older adults and those with kidney dysfunction or other comorbidities.

Beyond clinical efficacy, the results spotlight systemic issues in cancer care. New antibody–drug conjugates and immunotherapy combinations come with high costs and complex safety monitoring needs, which can widen disparities if access is determined by insurance coverage, geography, or socioeconomic status. Communities already underserved by oncology services — including rural populations, racial and ethnic minorities, and those with limited financial resources — may struggle to obtain these therapies without policy interventions.

Policymakers, payers and guideline panels will now confront decisions about approvals, reimbursement, and incorporation into standard treatment pathways. Equitable rollout will require attention to drug affordability, clinical infrastructure for administration and follow-up, and efforts to ensure diverse enrollment in confirmatory studies and real-world registries. As clinicians and advocacy groups parse the data, the challenge will be translating statistically robust trial results into outcomes that benefit all patients, not only those with the means to access elite cancer centers.

The ESMO presentations mark an important step forward in therapeutic options for HER2-positive breast cancer and muscle-invasive bladder cancer. The next phase will test health systems’ ability to deliver these advances fairly and to monitor long-term effects in broader patient populations.