LBA17 - Survival outcome of neoadjuvant endocrine therapy + trastuzumab and pertuzumab (ET+T+P) vs. de-escalated chemotherapy (CT)+T+P in hormone receptor positive (HR+)/HER2+ early breast cancer (EBC): WSG-TP-II trial

Background

(Neo)-adjuvant CT+T+P combinations (18-24 weeks) are considered as standard of care in all patients with HER2-positive EBC, irrespective of HR status. Although CT-free anti-HER2-combinations e.g. with ET are associated with lower rates of pathological complete response (pCR) in unselected patients with highly heterogeneous HR+/HER2+ disease (e.g. TP-II-pCR rates: 12 weeks of ET vs. Paclitaxel (Pac) +T+P: 23.7% vs. 56%), better safety and promising efficacy in selected subgroups have been observed. Furthermore, neoadjuvant 12xPac+T+P was associated with an excellent survival outcome in the WSG-ADAPT HR-/HER2+ trial. However, there is no prospective survival comparison for ET+T+P vs. a de-escalated CT-based regimen in HR+/HER2+ EBC so far.

Methods

WSG-TP II is a prospective, multicenter, randomized phase II trial that allocated patients with centrally confirmed HR+/HER2+ (ER and/or PR>1%) EBC (clinical stages I-III) to 12 weeks of neoadjuvant standard ET vs. Pac q1w both +T+P followed by standard ET +T+P for 1 year (+/- adjuvant CT). Omission of further adjuvant CT was recommended in all patients with pCR (primary endpoint). Event-free (EFS), distant disease free and overall survival (OS) are secondary endpoints.

Results

207 pts (55% postmenopausal, 58% cT2-4, 28% cN+) were randomized 1:1 (ET/CT: n=100/107). After a median follow up of 60 months 5-year EFS rates of ET vs. CT +T+P were 92.0% vs 94.8% (HR=1.29, 95% CI: 0.26-2.32, p= 0.65; of 13 EFS events only 1 vs. 4 were distant relapses or deaths as first event in the ET vs. CT arm). 5-year OS rates were 100% vs. 97.9% (n.s.). Only positive cN+ status was significantly associated with worse EFS by multivariable analysis. Additional CT after pCR was not associated with any significant survival impact in our study.

Conclusions

We have observed exceptionally excellent survival outcomes in HR+/HER2+ early BC if treated with neoadjuvant ET or Pac q1w (both for 12 weeks) +T+P followed by adjuvant pCR-guided CT and adjuvant T+P.+ET. Highly effective HER2-directed treatment offers an opportunity for the safe de-escalation of CT in early HR+/HER2+ EBC at least in patients achieving early pCR.

Clinical trial identification

NCT03272477.

Editorial acknowledgement

Legal entity responsible for the study

Palleos GmbH.

Funding

Roche.

Disclosure

O. Gluz: Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, Pierre Fabre, MSD, Pfizer, Gilead, Seagen, Agendia; Financial Interests, Personal, Invited Speaker: AstraZeneca, Exact Science; Financial Interests, Institutional, Coordinating PI: Roche, LIlly; Non-Financial Interests, Leadership Role: West German Study Group; Non-Financial Interests, Personal, Proprietary Information: West German Study Group. U.A. Nitz: Financial Interests, Personal, Invited Speaker, Role of RS and Ki 67 in decision making in HR+/HER2- EBC: Exact science. S. Kummel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Lilly, MSD, Novartis, Seagen, Pfizer, Pfizer, Roche, Somatex, Gilead, Sanofi, Hologic, PINK; Financial Interests, Personal, Invited Speaker: ExactScience, MSD, Lilly, Gilead, Roche, Sanofi, Daiichi Sankyo; Financial Interests, Personal, Ownership Interest, Minority Ownership: WSG Study Group; Financial Interests, Personal and Institutional, Coordinating PI: Roche, Novartis; Financial Interests, Institutional, Local PI: Roche, Novartis, Lilly, Somatex, AstraZeneca, MSD. J. Holtschmidt: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Roche, Seagen, Daiichi Sankyo, MSD; Financial Interests, Personal, Advisory Role: Palleos; Financial Interests, Personal, Advisory Board: Pfizer, Tesaro; Financial Interests, Institutional, Research Funding: Hologic; Financial Interests, Personal, Full or part-time Employment: GBG. A.D. Hartkopf: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Lilly, AstraZeneca, Agendia, Novartis, Seagen, Exact Science, MSD, Amgen; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Hexal, Clovis, GSK; Financial Interests, Personal, Non financial benefits, Travel: Pfizer, Roche, Gilead, AstraZeneca. K. Luedtke-Heckenkamp: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Stemline, Novartis, Pfizer, Seagen; Financial Interests, Personal, Non financial benefits, Travel: AstraZeneca; Financial Interests, Non financial benefits, Travel: Daiichi Sankyo, Gilead, Lilly, Stemline, MSD, Novartis, Pfizer, Roche. T. Schinköthe: Financial Interests, Personal, Full or part-time Employment: Cankado; Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Baxter, BMS. M.K. Graeser-Mayer: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Non financial benefits, Travel: Daiichi Sankyo. R. Würstlein: Financial Interests, Personal, Advisory Board: Agendia, Amgen, Apogheva, AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead, Lilly, MSD, Nanostring, Novartis, Pfizer, Pierre Fabre, Riemser, Roche, Sanofi Genzyme, Seagen, Stemline, Clinsol, Onkowissen, Paxman, Sidekick, Teva, Veracyte, Viatris; Financial Interests, Personal, Invited Speaker: Aristo, Clovis Oncology, Eisai, Palleos, PINK, FOMF, Aurikamed, Pomme Med, medconcept, MCI, Esteve, Wiley, iMEDInstitute, MediSeminar, Medicultus; Financial Interests, Personal, Writing Engagement: Hexal; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Coordinating PI: WSG, PINK; Financial Interests, Institutional, Local PI: BKFZ; Non-Financial Interests, Advisory Role: PINK, Brustkrebs Deutschland e.V., Junge Erwachsene Mit Krebs, AGO Kommission Mamma, AGSMO, DKG, TZM, CCC München, Mammamia. H. Kreipe: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Lilly, AstraZeneca, Exact Science. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuelligpharma, Viatris; Financial Interests, Personal, Other, IDMC: Roche; Financial Interests, Personal, Advisory Board: Sandoz-Hexal, Seagen, Aptitude Health, Pfizer, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Funding: BMS, Daiichi Sankyo, MSD, Roche, Seagen, TRIO, WSG, Gilead; Financial Interests, Institutional, Steering Committee Member: Lilly, Pierre Fabre; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Founding Editor: BreastCare Journal. All other authors have declared no conflicts of interest.