Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized...

Area of Science:

• Oncology
• Translational Medicine
• Clinical Trial Design

Background:

• Sequential adaptive trial designs are crucial for personalized medicine in oncology.
• Optimizing treatment strategies can improve patient outcomes and minimize toxicity.

Purpose of the Study:

• To evaluate datopotamab-deruxtecan (Dato-DXd) in combination with durvalumab as the initial therapy in a phase 2 neoadjuvant breast cancer trial.
• To assess the efficacy and safety of this combination in high-risk stage 2/3 breast cancer patients within the I-SPY2.2 adaptive trial framework.

Main Methods:

• The I-SPY2.2 trial employed a sequential adaptive design with three treatment blocks (A, B, C).
• Patients received Dato-DXd/durvalumab in block A, followed by subtype-tailored regimens.
• Treatment redirection was guided by imaging and biopsy data, with early surgical resection as an option.

Main Results:

• Datopotamab-deruxtecan/durvalumab exceeded success thresholds in the immune-positive subtype after block A.
• Pathologic complete response rates were 54% after Dato-DXd/durvalumab alone and 92% after blocks A+B, comparable to standard care.
• The treatment strategy also showed success in the hormone-negative/immune-negative subtype.

Conclusions:

• Datopotamab-deruxtecan and durvalumab represent a promising combination therapy for high-risk breast cancer.
• This regimen has the potential to eliminate the need for standard chemotherapy in a significant patient population, particularly the immune-positive subtype.
• The observed toxicities were manageable, with stomatitis being the most common side effect.