| Title: |
Datopotamab–deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial |
| Authors: |
Shatsky, Rebecca A; Trivedi, Meghna S; Yau, Christina; Nanda, Rita; Rugo, Hope S; Davidian, Marie; Tsiatis, Butch; Wallace, Anne M; Chien, A Jo; Stringer-Reasor, Erica; Boughey, Judy C; Omene, Coral; Rozenblit, Mariya; Kalinsky, Kevin; Elias, Anthony D; Vaklavas, Christos; Beckwith, Heather; Williams, Nicole; Arora, Mili; Nangia, Chaitali; Roussos Torres, Evanthia T; Thomas, Brittani; Albain, Kathy S; Clark, Amy S; Falkson, Carla; Hershman, Dawn L; Isaacs, Claudine; Thomas, Alexandra; Tseng, Jennifer; Sanford, Amy; Yeung, Kay; Boles, Sarah; Chen, Yunni Yi; Huppert, Laura; Jahan, Nusrat; Parker, Catherine; Giridhar, Karthik; Howard, Frederick M; Blackwood, M Michele; Sanft, Tara; Li, Wen; Onishi, Natsuko; Asare, Adam L; Beineke, Philip; Norwood, Peter; Brown-Swigart, Lamorna; Hirst, Gillian L; Matthews, Jeffrey B; Moore, Brian; Symmans, W Fraser; Price, Elissa; Heditsian, Diane; LeStage, Barbara; Perlmutter, Jane; Pohlmann, Paula; DeMichele, Angela; Yee, Douglas; van ’t Veer, Laura J; Hylton, Nola M; Esserman, Laura J |
| Source: |
Nature Medicine, vol 30, iss 12 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2024 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3211 Oncology and Carcinogenesis (for-2020); Biomedical Imaging (rcdc); Women's Health (rcdc); Clinical Trials and Supportive Activities (rcdc); Clinical Research (rcdc); Precision Medicine (rcdc); Breast Cancer (rcdc); Patient Safety (rcdc); Cancer (rcdc); 6.1 Pharmaceuticals (hrcs-rac); Cancer (hrcs-hc); 3 Good Health and Well Being (sdg); Humans (mesh); Female (mesh); Breast Neoplasms (mesh); Antibodies; Monoclonal (mesh); Middle Aged (mesh); Antineoplastic Combined Chemotherapy Protocols (mesh); Immunoconjugates (mesh); Adult (mesh); Aged (mesh); Neoplasm Staging (mesh); Neoadjuvant Therapy (mesh); Doxorubicin (mesh); Cyclophosphamide (mesh); Treatment Outcome (mesh); Trastuzumab (mesh); Camptothecin (mesh) |
| Time: |
3737 - 3747 |
| Description: |
Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody–drug conjugate, datopotamab–deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin–cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin–cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt9zr3q79x; https://escholarship.org/uc/item/9zr3q79x; https://escholarship.org/content/qt9zr3q79x/qt9zr3q79x.pdf |
| DOI: |
10.1038/s41591-024-03267-1 |
| Availability: |
https://escholarship.org/uc/item/9zr3q79x; https://escholarship.org/content/qt9zr3q79x/qt9zr3q79x.pdf; https://doi.org/10.1038/s41591-024-03267-1 |
| Rights: |
CC-BY-NC-ND |
| Accession Number: |
edsbas.F2FA8F14 |
| Database: |
BASE |