医学
内科学
三阴性乳腺癌
乳腺癌
肿瘤科
新辅助治疗
三重阴性
完全响应
癌症
化疗
作者
Laura M. Spring,Sara M. Tolaney,Geoffrey Fell,Veerle Bossuyt,Rachel Occhiogrosso Abelman,Bing Wu,Shyamala Maheswaran,Lorenzo Trippa,Amy Comander,Therese M. Mulvey,Sarah A. McLaughlin,Paula D. Ryan,Louise Ryan,Edward Abraham,Aron S. Rosenstock,Ana C. Garrido-Castro,Filipa Lynce,Beverly Moy,Steven J. Isakoff,Nadine Tung,Elizabeth A. Mittendorf,Leif W. Ellisen,Aditya Bardia
标识
DOI:10.1016/j.annonc.2023.11.018
摘要
Background
Sacituzumab govitecan (SG), a novel antibody–drug conjugate (ADC) targeting TROP2, is approved for pre-treated metastatic triple-negative breast cancer (mTNBC). We conducted an investigator-initiated clinical trial evaluating neoadjuvant (NA) SG (NCT04230109), and report primary results. Patients and methods
Participants with early-stage TNBC received NA SG for four cycles. The primary objective was to assess pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) to SG. Secondary objectives included overall response rate (ORR), safety, event-free survival (EFS), and predictive biomarkers. A response-guided approach was utilized, and subsequent systemic therapy decisions were at the discretion of the treating physician. Results
From July 2020 to August 2021, 50 participants were enrolled (median age = 48.5 years; 13 clinical stage I disease, 26 stage II, 11 stage III). Forty-nine (98%) completed four cycles of SG. Overall, the pCR rate with SG alone was 30% [n = 15, 95% confidence interval (CI) 18% to 45%]. The ORR per RECIST V1.1 after SG alone was 64% (n = 32/50, 95% CI 77% to 98%). Higher Ki-67 and tumor-infiltrating lymphocytes (TILs) were predictive of pCR to SG (P = 0.007 for Ki-67 and 0.002 for TILs), while baseline TROP2 expression was not (P = 0.440). Common adverse events were nausea (82%), fatigue (76%), alopecia (76%), neutropenia (44%), and rash (48%). With a median follow-up time of 18.9 months (95% CI 16.3-21.9 months), the 2-year EFS for all participants was 95%. Among participants with a pCR with SG (n = 15), the 2-year EFS was 100%. Conclusions
In the first NA trial with an ADC in localized TNBC, SG demonstrated single-agent efficacy and feasibility of response-guided escalation/de-escalation. Further research on optimal duration of SG as well as NA combination strategies, including immunotherapy, are needed.