Dr Yee on Neoadjuvant Datopotamab Deruxtecan Plus Durvalumab in Early-Stage Breast Cancer

Douglas Yee, MD, director, Masonic Cancer Center at the University of Minnesota, discusses the results from phase 2 I-SPY2.2 trial (NCT01042379) for combination of datopotamab deruxtecan (Dato-DXd) and durvalumab (Imfinzi) in the neoadjuvant setting for breast cancer.

Findings from the I-SPY2.2 trial presented at the 2024 ASCO Annual Meeting by Rebecca A. Shatsky, MD, of the University of California, San Diego Medical Center, highlighted pathologic complete responses (pCR) achieved with this combination therapy. In this arm of the trial, 33% of patients (n = 106) were able to proceed to surgery without chemotherapy following 4 cycles of Dato-DXd plus durvalumab. Notably, 43%) of patients (n = 47) in the immune-positive subgroup achieved a pCR following 4 cycles with the combination, and the moddeled pCR rate for patients within this subgroup was 65% (95% CI, 47%-83%). This outcome successfully surpassed the prespecified goal of a 40% for this combination.

Yee notes that this patient cohort included some individuals with hormone receptor–positive disease, demonstrating the potential of this regimen to improve pCR rates across different breast cancer subtypes when used within a biomarker-defined population.

These results suggest Dato-DXd plus durvalumab may offer an effective alternative to traditional chemotherapy in the neoadjuvant setting, particularly for patients identified as immune-positive through predictive biomarkers, Yee explains. The trial's observed pCR rates in this subgroup highlight the importance of precision medicine in tailoring neoadjuvant treatments to individual patients' tumor biology, he adds.

Yee suggests that this combination therapy could lead to a shift away from conventional chemotherapy approaches, paving the way for more targeted therapies and less toxic treatment options in the neoadjuvant setting.

These results warrant further investigation in larger trials to confirm the efficacy and safety of this regimen and to explore its potential integration into standard treatment protocols for breast cancer, Yee concludes.