HR+/HER2+ BC is a distinct entity associated with different molecular and therapeutic features compared to HR-/HER2+ BC. The HER2 antibody drug conjugate T-DM1 is highly effective in metastatic and early HER2+ BC. So far, no survival data for de-escalated T-DM1-based (neo)adjuvant regimens without systemic chemotherapy (CT) are available. Here, we present first survival data from ADAPT-TP.
The prospective WSG-ADAPT-TP phase II-trial is part of the ADAPT-umbrella protocol (NCT NCT01779206): 375 patients (pts) with HR+/HER2+ BC were randomized to 12 weeks of T-DM1 +/- standard ET and trastuzumab+ET q3w (ratio 1:1:1). Primary endpoint was pCR (ypT0/is/ypN0) (previously published: T-DM1/T-DM1+ET/T+ET: 41%/42%/15%). Secondary endpoints: safety, 5-y DFS, OS, translational research. Omission of further CT was allowed in all pts with pCR after 12-weeks study therapy.
After median follow-up of 5 years, no significant differences between study arms were observed regarding DFS (T-DM1/T-DM1+ET/T+ET 5-y rate: 88.9%, 85.3%, and 84.6%) and OS (97.2%, 96.4% and 96.3%). pCR (vs. non-pCR) after the 12-week study treatment was strongly associated with improved DFS (5y DFS 92.7% vs. 82.7, HR=0.40, 95% CI 0.18-0.85). Among 117 pts with pCR, no further CT was given in 41 pts (35%). Significant differences between CT-treated vs. non-treated pCR pts regarding baseline characteristics were only observed for age (median 50y vs. 56y, p=0.005); similar 5y DFS was observed in both groups (92.1% (95%-CI: 78-97%) vs. 93% (84-97%)). Only 3 deaths occurred in pts with pCR.
Early pCR after 12 weeks of therapy was strongly associated with improved outcome in ADAPT TP and may serve as a predictive marker for CT treatment (de)-escalation. Despite substantially higher pCR rates, T-DM1 +/- ET was not associated with different DFS or OS vs. T+ET, most likely due to standard CT, given to all non-pCR pts and most pCR pts or small sample size of study. Excellent 93% 5y DFS in pts with pCR after only 12 weeks of T-DM1 +/- ET (even w/o further CT) is promising and may serve as a basis for further prospective trials addressing omission of CT overtreatment in carefully selected patients with HER2+ early BC.
Clinical trial identification
Legal entity responsible for the study
West German Study Group.
N. Harbeck: Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Seattle Genetics. U. Nitz: Honoraria (self), Advisory/Consultancy: Amgen; AstraZeneca; Genomic Health; Novartis; Pfizer; Pierre Fabre; Roche; Zodiac Pharma. S. Kuemmel: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, Somatex Medical Technologies, Daiichi Sankyo, pfm medical, Pfizer, MSD, Lilly, SonoscapeRoche, Genomic Health, Novartis, AstraZeneca, Amgen, Celgene, Somatex Medical Technologies, Daiichi Sanky. M. Braun: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca, Celgene, Eisai, Genomic Health, GalaxoSmithKline, Medac, Novatis, Pfizer, Roche, RTI Surgical, Teva. J. Tio: Travel/Accommodation/Expenses: Roche. B. Aktas: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer, Roche Pharma, Novartis Pharma, AstraZeneca, Amgen, Tesaro Bio Germany, PharmaMar, Eisai. W. Malter: Honoraria (self), Advisory/Consultancy: Nanostring, Celgene, Roche. R. Wuerstlein: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Clinsol, Daiichi-Sankyo, Eisai, Genomic Health, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, NanoString, Novartis, Odonate, Paxman, Palleos, Pfizer, Pi. H. Kreipe: Honoraria (self), Advisory/Consultancy: Roche, Novartis, AstraZeneca, Genomic Health. All other authors have declared no conflicts of interest.