Datopotamab-deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial.

Autor:	Shatsky RA; University of California San Diego, San Diego, CA, USA., Trivedi MS; Columbia University, New York, NY, USA., Yau C; University of California San Francisco, San Francisco, CA, USA., Nanda R; University of Chicago, Chicago, IL, USA., Rugo HS; University of California San Francisco, San Francisco, CA, USA., Davidian M; North Carolina State University, Raleigh, NC, USA., Tsiatis B; North Carolina State University, Raleigh, NC, USA., Wallace AM; University of California San Diego, San Diego, CA, USA., Chien AJ; University of California San Francisco, San Francisco, CA, USA., Stringer-Reasor E; University of Alabama at Birmingham, Birmingham, AL, USA., Boughey JC; The Mayo Clinic, Rochester, MN, USA., Omene C; Cooperman Barnabas Medical Center, New Brunswick, NJ, USA.; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA., Rozenblit M; Yale University, New Haven, CT, USA., Kalinsky K; Emory University, Atlanta, GA, USA., Elias AD; University of Colorado, Denver, CO, USA., Vaklavas C; University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA., Beckwith H; University of Minnesota, Minneapolis, MN, USA., Williams N; The Ohio State University, Columbus, OH, USA., Arora M; University of California Davis, Davis, CA, USA., Nangia C; HOAG Family Cancer Institute, Newport Beach, CA, USA., Roussos Torres ET; University of Southern California, Los Angeles, CA, USA., Thomas B; Sparrow Health System, Lansing, MI, USA., Albain KS; Loyola University Chicago Stritch School of Medicine, Chicago, IL, USA., Clark AS; University of Pennsylvania, Philadelphia, PA, USA., Falkson C; University of Rochester Medical Center, Rochester, NY, USA., Hershman DL; Columbia University, New York, NY, USA., Isaacs C; Lombardi Comprehensive Cancer Center Georgetown University, Washington, DC, USA., Thomas A; Wake Forest University, Winston-Salem, NC, USA., Tseng J; City of Hope Orange County Lennar Foundation Cancer Center, Irvine, CA, USA., Sanford A; Sanford Health, Sioux Falls, SD, USA., Yeung K; University of California San Diego, San Diego, CA, USA., Boles S; University of California San Diego, San Diego, CA, USA., Chen YY; University of California San Francisco, San Francisco, CA, USA., Huppert L; University of California San Francisco, San Francisco, CA, USA., Jahan N; University of Alabama at Birmingham, Birmingham, AL, USA., Parker C; University of Alabama at Birmingham, Birmingham, AL, USA., Giridhar K; The Mayo Clinic, Rochester, MN, USA., Howard FM; University of Chicago, Chicago, IL, USA., Blackwood MM; Cooperman Barnabas Medical Center, New Brunswick, NJ, USA., Sanft T; Yale University, New Haven, CT, USA., Li W; University of California San Francisco, San Francisco, CA, USA., Onishi N; University of California San Francisco, San Francisco, CA, USA., Asare AL; University of California San Francisco, San Francisco, CA, USA.; Quantum Leap Healthcare Collaborative, San Francisco, CA, USA., Beineke P; Quantum Leap Healthcare Collaborative, San Francisco, CA, USA., Norwood P; Quantum Leap Healthcare Collaborative, San Francisco, CA, USA., Brown-Swigart L; University of California San Francisco, San Francisco, CA, USA., Hirst GL; University of California San Francisco, San Francisco, CA, USA., Matthews JB; University of California San Francisco, San Francisco, CA, USA., Moore B; Wake Forest University, Winston-Salem, NC, USA., Symmans WF; University of Texas MD Anderson Cancer Center, Houston, TX, USA., Price E; University of California San Francisco, San Francisco, CA, USA., Heditsian D; University of California San Francisco, San Francisco, CA, USA., LeStage B; University of California San Francisco, San Francisco, CA, USA., Perlmutter J; The Gemini Group, Ann Arbor, MI, USA., Pohlmann P; University of Texas MD Anderson Cancer Center, Houston, TX, USA., DeMichele A; University of Pennsylvania, Philadelphia, PA, USA., Yee D; University of Minnesota, Minneapolis, MN, USA., van 't Veer LJ; University of California San Francisco, San Francisco, CA, USA., Hylton NM; University of California San Francisco, San Francisco, CA, USA., Esserman LJ; University of California San Francisco, San Francisco, CA, USA. laura.esserman@ucsf.edu.
Jazyk:	angličtina
Zdroj:	Nature medicine [Nat Med] 2024 Sep 14. Date of Electronic Publication: 2024 Sep 14.
DOI:	10.1038/s41591-024-03267-1
Abstrakt:	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 that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.ClinicalTrials.gov registration: NCT01042379 . (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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