Abstract PD18-06: Image-guided optimization of neoadjuvant chemotherapy duration in stage II and III HER2-positive breast cancer: radiologic and pathologic complete response (pCR) rates in the multicenter phase 2 TRAIN-3 study (BOOG 2018-01)

Background pCR rates in stage II – III HER2-positive breast cancer have greatly improved since the addition of HER2 targeted agents to neoadjuvant chemotherapy and are associated with excellent long-term survival. While longer treatment regimens increase pCR rate, early complete responses are also common. We evaluated an image-guided approach to tailor chemotherapy duration based on the identification of early complete responders. Methods 45 hospitals across the Netherlands participated in the phase 2 TRAIN-3 trial. Patients received neoadjuvant systemic treatment consisting of paclitaxel, trastuzumab, carboplatin and pertuzumab (PTC-Ptz). Response to treatment was monitored every three cycles and patients were referred for surgery in case of a radiologic complete response (rCR) or after a maximum of 9 cycles. RCR was defined as the absence of pathological enhancement on MRI breast plus negative vacuum assisted core biopsies in case of hormone-receptor positive (HR+) tumors. In addition, negative fine needle aspiration or lymph node biopsy was required in patients with nodal involvement at baseline. The primary endpoint was 3-year event-free survival (EFS). Here, we report locally assessed rCR and pCR rates after 3, 6 and 9 cycles, the negative predictive value of rCR assessment and the incidence of adverse events (AEs). Analyses are stratified by HR-status. Results We included 467 patients between April 2019 and May 2021. Median age was 51 years, 69% had stage II disease and 232 had HR+ tumors. 33.6% of HR- patients and 15.5% of HR+ patients achieved pCR after 3 cycles of PTC-Ptz (see table). The NPV was higher in HR- patients and independent of the number of cycles. AE evaluation is currently ongoing. Conclusion Three cycles of PTC-Ptz induce an early pCR in one in three HR- and one in six HR+ tumors in patients with stage II-III HER2+ breast cancer. Dynamic contrast enhanced MRI-based response evaluation identifies these patients with ±87% certainty in HR- disease and ±58% in HR+ disease. Continuation of PTC-Ptz after 6 cycles further improves pCR rates and can be considered to reduce the need for adjuvant T-DM1. Efficacy and safety of this image-guided approach to tailor treatment duration need to be confirmed with follow-up in EFS and OS analyses. Table 1: Cumulative rCR & pCR according to HR-status *Including patients who underwent surgery for other reasons than rCR Citation Format: Anna van der Voort, Mette S. van Ramshorst, Rob Kessels, Ingrid A. Mandjes, Inge Kemper, Mariëtte J. Agterof, Wim A. van der Steeg, Joan B. Heijns, Marlies L. van Bekkum, Ester J. Siemerink, Philomeen M. Kuijer, Astrid Scholten, Jelle Wesseling, Marie-Jeanne T.F.D. Vrancken Peeters, Ritse M. Mann, Gabe S. Sonke. Image-guided optimization of neoadjuvant chemotherapy duration in stage II and III HER2-positive breast cancer: radiologic and pathologic complete response (pCR) rates in the multicenter phase 2 TRAIN-3 study (BOOG 2018-01) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-06.