Real-world data on post-neoadjuvant trastuzumab emtansine to benchmark DESTINY-Breast-05 and -11 emerging paradigms.

Abstract

e12516 Background: Post-neoadjuvant trastuzumab emtansine (T-DM1) is the standard of care for patients (pts) with HER2-positive early breast cancer (eBC) with residual disease (RD) after neo-adjuvant therapy (NAT). Emerging data show that trastuzumab deruxtecan (T-DXd) is redefining (neo-)adjuvant strategies according to DESTINY-Breast (DB)-05 and -11 trials. We conducted a real-world benchmarking study of post-neoadjuvant T-DM1 to quantify contemporary outcomes and contextualize emerging T-DXd strategies in routine practice. Methods: We included all consecutive pts with evidence of RD after trastuzumab-based NAT, receiving T-DM1 (≥1 cycle) from Jan-2020 to Aug-2024 at the European Institute of Oncology (Milan). The primary endpoint was the 3-year invasive disease-free survival (3y-iDFS) rate. Results: A total of 187 pts was included, of which 55% were premenopausal, 71% had hormone receptor (HR)-negative disease, 75% had HER2 3+, and 21% had node-positive eBC at diagnosis. Prior pertuzumab or anthracyclines-based NAT were used in 32% and in 82% of pts, respectively. Adjuvant ovarian function suppression was received by 84% of premenopausal pts with HR-positive eBC. At a median follow up of 30.4 months (range: 3.4-68.1), we observed a real-world 3y-iDFS rate of 97% (range: 95%-100%). Among the 6 pts with invasive disease recurrence, 5 had distant dissemination, including 1 brain recurrence. A high (> 30%) baseline Ki67 was detected in all pts with a relapse, compared to 44% of disease-free pts. Considering baseline characteristics, 41% of pts did not comply neither DB-11 nor DB-05 inclusion criteria; 32% were eligible only for DB-11 (“DB-11 only”); 25% were eligible for both; 3% were eligible only for DB-05. Among pts with a relapse, 4 were eligible for both trials, while 2 pts were ineligible for either. Conclusions: Post-neoadjuvant T-DM1 shows an excellent real-world effectiveness profile, with a low incidence of invasive disease recurrences. Notably, a large fraction of pts treated in routine practice would not have met DB-05/-11 trial eligibilities, and none with an iDFS event belonged to the “DB-11 only” population. These data highlight the value of real-world benchmarking to contextualize trial evidence and guide integration of antibody–drug conjugates in the curative scenario.