LBA14 - Impact of age, recurrence score (RS) and ovarian function suppression (OFS) on endocrine response to short preoperative endocrine therapy (ET): Analysis of ADAPT and ADAPTcycle trials

Background

Benefit of chemotherapy (CT) addition to ET remains controversial in premenopausal (pre) patients (pts) with 0-3 positive LNs (N0-1) and RS ≤25. In ADAPT, excellent outcome was observed in young N0-1 pts and ET response after short-term preoperative ET and RS 12-25 with ET alone. Here, we investigate impact of age, RS, and OFS on ET response, in ADAPT and its validation in the first part of ongoing phase III ADAPTcycle trial.

Methods

In ADAPT, pts with clinical high-risk HR+/HER2- EBC received 3w of induction standard ET prior to surgery or core biopsy, and then ET-alone if N0-1 and RS 0-11 or 12-25 ± post-endocrine Ki67_post≤10%, or CT if Ki67_post>10%. In ADAPTcycle (n=5000 to screen), N0-1 pts with RS>25 and Ki67_post≤10% and N2-3 pts with RS≤25 and ET-response are randomized to (neo)adjuvant CT or AI+ribociclib.

Results

5938 pts included (ADAPT, n=3666; Acycle, n=2272): 1975 pts ≤50y/pre, 424 pts ≤40y. ET in ≤50y/pre pts included tamoxifen (98% ADAPT, 70.4% Acycle), TAM+OFS (15.2% Acycle) and AI+OFS (14.4% Acycle); >80% of >50y or post pts had AI. Baseline ER did not differ significantly between age groups ≤40, >40-50- and >50 ys. Mean baseline RS scores were higher in pts ≤40ys, but comparable between pts aged >40-50 and >50. ET-response rates varied substantially by type of ET, age, and RS in particular if no OFS in premenopausal pts. In ADAPT, ET-response was associated with improved iDFS in all age cohorts, independent of baseline Ki67. Table: 000LBA14

* OFS data in ADAPTCycle only, in ADAPT, only 2% AI+OFS in pts ≤50 ys ** only few pts treated by OFS in >50 ys, pre group

Conclusions

ET-response after TAM or AI according to RS groups was similar in both trials, but adding OFS to TAM or AI substantially improves ET-response in pre pts ≤ 50y, rendering similar results as in AI-treated post pts. ET-response assessment provides clinically relevant information for CT-decision making in pre ≤50y N0-1 pts in addition to gene expression testing.

Clinical trial identification

NCT01779206.

Editorial acknowledgement

Legal entity responsible for the study

West German Study Group.

Funding

Exact Science, Novartis, Amgen, Bristol Myers Squibb.

Disclosure

O. Gluz: Financial Interests, Personal, Advisory Board: Roche, Lilly, Amgen, Novartis, Pierre Fabre, MSD, Celgene, Pfizer, Gilead, Molecular Health, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Exact Science; Financial Interests, Institutional, Invited Speaker: Roche; Non-Financial Interests, Leadership Role: West German Study Group; Non-Financial Interests, Personal, Proprietary Information: West German Study Group. U.A. Nitz: Financial Interests, Institutional, Other, Honoraria: Agendia, Amgen, Celgene, Genomic Health, Nanostring Technologies, Novartis Pharma, Pfizer Pharmaceuticals, Roche/Genentech, Teva; Financial Interests, Institutional, Advisory Role: Genomic Health, Roche, Seagen; Financial Interests, Institutional, Funding: Agendia, Amgen, Celgene, Genomic Health, Nano String Technologies, Roche, Sanofi; Financial Interests, Institutional, Expert Testimony: Genomic Health; Financial Interests, Institutional, Other, Travel Expenses: Genomic Health, Pfizer Pharmaceuticals, Roche; Other, Institutional, Other, Co-Director: WSG. S. Kuemmel: Financial Interests, Institutional, Advisory Role: Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Genomic Health/Exact Sciences, Lilly, MSD, Novartis, Seagen, Lilly, Pfizer, pfm Medical, Roche, Somatex, Gilead; Financial Interests, Institutional, Funding: Roche, Novartis; Financial Interests, Institutional, Other, Travel Expenses: Roche, Daiichi Sankyo; Financial Interests, Institutional, Other, Non-CME Services: Somatex, Roche, Novartis, Lilly; Financial Interests, Institutional, Other, Personal Fees: Roche, Novartis; Financial Interests, Institutional, Ownership Interest, WSG: WSG; Financial Interests, Institutional, Other, Co-Director: WSG. M. Braun: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Exact Sciences, Novartis, Pfizer, Roche, Teva, MSD; Financial Interests, Institutional, Advisory Role: AstraZeneca, Exact Sciences, Novartis, Puma, Roche; Financial Interests, Institutional, Other, Travel Expenses: AstraZeneca, Celgene, Medac, Novartis, Roche, Daiichi Sankyo. M. Thill: Financial Interests, Institutional, Other, Honoraria: Amgen, AstraZeneca, Celgene, Clovis, Eisai, Exact Sciences, Daiichi Sankyo, GSK, Hexal, Lilly, Medtronic, MSD, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical; Financial Interests, Institutional, Advisory Role: Amgen, AstraZeneca, Biom'Up, Celgene, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Lilly, MSD, Norgine, Neodynamics, Novartis, Pfizer, pfm Medical, Pierre-Fabre, Roche, RTI Surgical, Sysmex; Financial Interests, Institutional, Funding: Exact Sciences, Neodynamics, RTI Surgical; Financial Interests, Institutional, Other, Travel Expenses: Amgen, Celgene, Exact Sciences, pfm Medical, Roche; Financial Interests, Institutional, Other: Celgene, ClearCut, Roche, pfm Medical. B. Aktas: Financial Interests, Institutional, Other, Honoraria: Pfizer, Roche Pharma, Merck Sharp & Dohme, Onkowissen.de, Novartis Pharma, AsstraZeneca, PharmaMar, Lilly, promedicis. P. Wimberger: Financial Interests, Other, Honoraria: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche, Teva, Eisai, Clovis, GSK; Financial Interests, Advisory Board: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche, Teva, Eisai, Clovis, GSK; Financial Interests, Funding: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche, Clovis, GSK. M. Zaiss: Financial Interests, Advisory Role: Roche, Jannsen, Novartis, AstraZeneca, Gilead, AbbVie; Financial Interests, Speaker’s Bureau: Roche, Pfizer. M. Graeser: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Other, Travel Expenses: Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Member: WSG. A.D. Hartkopf: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Agendia, Amgen, Clovis, Daichii Sankyo, Eisai, Exact Sciences, Gilead, GSK, Lilly, Hexal, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen; Financial Interests, Institutional, Advisory Role: AstraZeneca, Agendia, Amgen, Clovis, Daichii Sankyo, Eisai, Exact Sciences, Gilead, GSK, Lilly, Hexal, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen; Financial Interests, Institutional, Funding: Exat Sciences; Financial Interests, Institutional, Other, Travel Expenses: Pfizer, Roche, Gilead, AstraZeneca; Financial Interests, Institutional, Speaker’s Bureau: AstraZeneca, Eisai, Exact Sciences, Gilead, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Seagen. R.E. Kates: Financial Interests, Institutional, Other, Honoraria: Amgen, AstraZeneca, Genomic Health, Novartis, Pfizer, Roche, Zodiac Pharma; Financial Interests, Institutional, Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen; Financial Interests, Institutional, Funding: WSG. P. Schmid: Financial Interests, Institutional, Research Grant: Astellas Pharma, AstraZeneca, Medivation Inc.; Financial Interests, Institutional, Advisory Role: AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, F. Hoffmann - La Roche, Merck; Financial Interests, Personal, Research Grant: F. Hoffmann - La Roche, Genentech, Novartis; Financial Interests, Institutional, Advisory Role, Honoraria: Novartis; Financial Interests, Other, Data and Safety Monitoring: Novartis; Financial Interests, Institutional, Funding: OncoGenexPharmaceuticals, Inc.; Financial Interests, Advisory Role: Pfizer; Financial Interests, Advisory Role, Honoraria: Puma Biotechnology. H. Kreipe: Financial Interests, Other, Honoraria: Roche Pharma, Novartis, Genomic Health, AstraZeneca, Lilly, Pfizer; Financial Interests, Advisory Role: Roche Pharma, Genomic Health, AstraZeneca. N. Harbeck: Financial Interests, Other, Honoraria: AstraZeneca, Genomic Health, Amgen, Novartis, Pfizer, Pierre Fabre, Roche, Zodiac Pharma; Financial Interests, Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen; Financial Interests, Institutional, Funding: Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech; Financial Interests, Other, Fees for Non-CME Services: Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, MSD, Novartis, Pierre Fabre, Pfizer, Roche, SeaGen; Financial Interests, Ownership Interest, WSG: WSG; Financial Interests, Other, Co-Director: WSG. All other authors have declared no conflicts of interest.