Background: Optimal use of de-escalated, particularly chemotherapy(CT)-free, neoadjuvant regimens in HER2+ early breast cancer (EBC) is currently unclear as there are limited survival data so far. In ADAPT-HR-/HER2+, we previously showed an excellent pCR rate of 90% after 12-week neoadjuvant paclitaxel (Pac) +pertuzumab (P) +trastuzumab (T) and a substantial and clinically meaningful pCR rate of 34% after P+T alone in HR-/HER2+ EBC. Here, we present first survival data. Methods: The prospective multicenter WSG-ADAPT-HR-/HER2+ phase II-trial is part of the ADAPT-umbrella protocol. Patients with cT1-cT4c, cN0-3 HR-/HER2+ EBC (n = 134) were randomized to 4 cycles of P+T +/- pac d1,8,15 q3w. All tumors were HR-negative (ER and PR < 1%) and HER2-positive (central lab, i.e., 2+ FISH positive or 3+ by immunohistochemistry. Primary endpoint was pCR (ypT0/is/ypN0); omission of further CT was allowed in pts with pCR. Trial objective was to compare pCR in P+T+pac arm vs. early responders in P+T arm (defined as low cellularity and/or Ki67 decrease >30% after 3 weeks). The trial was stopped early due to the observed pCR superiority in the P+T+pac arm. Secondary endpoints included safety, 5-y (distant)-DFS, OS and translational research. Cox-regression analysis was applied. PAM50 subtype was assessed using the BC360 panel. Results: 134 patients were randomized to P+T (n = 92) or P+T+pac (n = 42). 60% of tumors were cT2-4, 42% clinically node-positive. After a median follow-up of 5 years, no significant differences between study arms were observed regarding DFS, dDFS, and OS; only 13 iDFS events (7 dDFS) were observed in the whole ITT population. pCR (vs. non-pCR) after the 12-week study treatment (irrespective of study arm) was strongly associated with improved iDFS (5y DFS 98.5% vs. 82%, HR = 0.14, 95% CI 0.03-0.64). Of the 69 patients with pCR, 39 (56.5%) received no further CT (P+T arm: n = 9, 29% vs. (P+T+pac arm n = 30, 79%); only 1 distant relapse (1.4%) was observed in these patients. In the CT-free P+T arm, no pCR was observed in patients with low HER2 expression (IHC 1+/2+ and FISH positive) and/or basal-like subtype by PAM50 (n = 17, 19%). In the total study population, low HER2 expression and/or no early response was strongly associated with worse dDFS (p =.029) and iDFS (p =.068). No new safety signals were observed. Conclusions: For the first time, we have shown both excellent pCR and survival in patients treated by de-escalated neoadjuvant CT+P+T irrespective of further CT use in a prospective multicenter study. Investigation of CT-free regimens may need to be focussed on selected patients only (e.g. with high HER2 expression/non-basal-like tumors). In ADAPT HR-/HER2+, early pCR after only 12 weeks of neoadjuvant P+T+pac was strongly associated with improved outcome and may thus serve as a predictive clinical marker for further treatment (de)-escalation. Clinical trial information: NCT01779206