Background: De-escalation of adjuvant therapy following pathologic complete response (pCR) to an abbreviated neoadjuvant regimen in HER2-positive (HER2+) breast cancer is the focus of a recently initiated national trial. However the feasibility of this approach, and its appeal to patients (pts) and providers, has not been formally investigated. Methods: We conducted a single arm pilot trial to determine the feasibility of de-escalated adjuvant therapy (HP-only) in patients with pCR following neoadjuvant THP. Eligible pts had clinical anatomic stage II-III treatment-naïve HER2+ breast cancer. All pts received weekly paclitaxel x12 doses, and HP every 3 weeks x4 doses (up to 6 doses allowed in case of surgical delay). The primary objective was to assess adherence to protocol-specified antibody doublet therapy (HP-only, without cytotoxic chemotherapy) in the adjuvant setting among pts with pCR (ypT0/isN0) following neoadjuvant THP; the primary endpoint was receipt of adjuvant cytotoxic chemotherapy, assessed 3 months post-operatively. Trastuzumab emtansine (T-DM1) was not considered cytotoxic chemotherapy. Among pts with pCR to THP, de-escalation would be deemed infeasible if the true rate of adherence to HP-only were <80%. With sample size of 100 pts, the study was designed to have >90% power to reject the null if the true rate of adherence were >95% (Binomial exact test; one-sided alpha=0.05). Questionnaires were administered and records were reviewed to assess pts’ and physicians’ decision-making about adjuvant systemic therapy following pCR and non-pCR. Results: 98 pts received at least one dose of THP on study. Median age was 50 yrs (range 24-78), pts were 99% female, 86% had stage II/14% stage III tumors, 32% ER/PR negative. No pts progressed during neoadjuvant THP. Five pts had incomplete clinical response following THP and received AC prior to surgery. They were classified as non-pCR and censored from further analyses. At the time of analysis, 93 pts were evaluable for response to neoadjuvant therapy (1 pt withdrew from study early; 4 pts had not reached surgery by the data cutoff). Overall pCR rate was 55% (51/93 pts); 10%, 28%, and 2% of pts had RCB I, II, and III responses, respectively (this excluded patients who received AC preoperatively). Of 51 pts who had pCR to THP, 40 had verified data available regarding adjuvant chemotherapy receipt at data cutoff. 39/40 pts (97.5%, 95% CI 86.8-99.9%) who had pCR did not receive adjuvant cytotoxic chemotherapy, meeting the trial’s prespecified threshold for declaring this a feasible approach (primary endpoint), though data remain pending for 11 pts with pCR and will be available at presentation. Of 30 pts who did not experience pCR to THP and had adjuvant chemotherapy status verified at data cutoff, 14/30 pts received adjuvant cytotoxic chemotherapy, and 16/30 pts did not receive adjuvant chemotherapy. The most common reasons cited by pts for non-receipt of adjuvant cytotoxic chemotherapy, despite residual disease at surgery, were (N=21): plan for adjuvant T-DM1 alone (67% of pts), good response to preop chemo (38% of pts), and plan for adjuvant hormonal therapy (24% of pts). The most common reason cited by treating physicians for non-administration of adjuvant chemotherapy, despite residual disease at surgery, was plan for adjuvant T-DM1 (17/21 (81%) physicians). With brief follow-up (median 10.2 mos), there were no breast cancer recurrences. Conclusions: De-escalation of adjuvant cytotoxic chemotherapy among pts who experience pCR in early stage HER2+ breast cancer appears to be an acceptable approach for both pts and physicians, though data are not yet complete and will be updated at the time of presentation. The long-term efficacy of this approach will be determined in the ongoing national CompassHER2-pCR trial.

Citation Format: Adrienne G. Waks, Neelam V. Desai, Tianyu Li, Philip D. Poorvu, Ann H. Partridge, Natalie Sinclair, Laura M. Spring, Meredith Faggen, Michael Constantine, Jillian C. Alberti, Julia Deane, Shoshana M. Rosenberg, Sara M. Tolaney, Ian E. Krop, Nadine M. Tung, Nabihah Tayob, Tari A. King, Elizabeth A. Mittendorf, Eric P. Winer. The DAPHNE trial: A feasibility study of chemotherapy de-escalation based on response to neoadjuvant paclitaxel-HP (THP) in HER2-positive breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD3-05.