Abstract 121P
Background
In ADAPTcycle, post-endocrine central Ki67 (Ki67post) ≤10% was defined as endocrine therapy response (ETR) to guide therapy decisions in HR+ HER2- EBC. Here, concordance between local and central Ki67 measurements was evaluated to assess the robustness of this factor for routine clinical application.
Methods
In ADAPTcycle (n=5,290 screened, 1,670 randomized by 06/23; 84 sites in Germany), patients with intermediate-risk EBC based on OncotypeDX and ETR were randomized to (neo)adjuvant chemotherapy (CT) followed by ET vs ribociclib + AI (premenopausal: +GnRH). Concordance of local with central Ki67 was quantified (baseline (BL), post-ET), focusing on ETR assessment and examined separately in patients >50 years (C>50) and ≤50 years (C≤50).
Results
Mean BL central (n=4903) vs. local (n=4972) Ki67 values were 24.9% vs. 26.9% in the overall cohort (OC), 24.9% (n=1,613) vs. 25.7% (n=1,646) in C≤50 and 24.9% (n=3,235) vs. 27.5% (n=3,318) in C>50, respectively. In 4664 tumors (OC) available for comparison at BL, 4003 (85.8%) had Ki67>10% locally, of which only 265 (6.6%) (91/1309 (7.0%) in C≤50, 174/2688 (6.5%) in C>50) had central Ki67≤10%. Mean Ki67post central (n=4,429) vs. local (n=2,786) values were 10.5% vs. 12.9% respectively. In 2590 cases available for comparison, ETR was 64.2% centrally (60.7% locally). Of 1729 C>50 cases, 1240 (71.2%) showed ETR centrally (67.7% locally) and in C≤50 cohort 423/861 (49.1%) cases centrally (46.6% locally). The sensitivity of local ETR to detect central “ground truth” was 82.1% (OC); the corresponding specificity (i.e., detecting non-response) was 77.8%. Only 206/1571 (13.1%) locally defined ETR (8% of tumors with local Ki67post ≤5%) were central non-ETR, i.e., the positive predictive value (PPV) of local ETR was 86.9%. PPV was higher in C>50 than C≤50 (89.6%, vs. 79.1%) with higher sensitivity in C>50 than C≤50 (84.5% vs. 74.9%) but lower specificity (75.1% vs. 80.8%).
Conclusions
The high PPV and overall high concordance of BL Ki67 >10% and Ki67post in OC, C>50 and C≤50 demonstrate that local assessment of ETR using Ki67 is feasible and reliable in clinical routine and results in a low risk of under-therapy if used as a criterion to omit CT.
Clinical trial identification
NCT04055493.
Legal entity responsible for the study
West German Study Group.
Funding
West German Study Group, Novartis, Genomic Health.
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, Invited Speaker: 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, Institutional, Other, Co-Director: West German Study Group. 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: Exact Science, MSD, Lilly, Gilead, Roche, Sanofi, Daiichi Sankyo; Financial Interests, Personal, Ownership Interest, Minority Ownership: WSG Study Group; Financial Interests, Personal and Institutional, Invited Speaker: Roche, Novartis; Financial Interests, Institutional, Invited Speaker: Roche, Novartis, Lilly, Somatex, AstraZeneca, MSD. 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, Personal, Advisory Board: Agendia, AstraZeneca, Becton and Dickinson, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Novartis, Onkowissen, Organon, Pfizer, pfm medical, Pierre Fabre, Roche, Seagen, Vifor, Viatris; Financial Interests, Personal, Invited Speaker: Agendia, Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, GSK, Lilly, MSD, Neodynamics, Novartis, Pfizer, pfm medical, Roche, Seagen, Sirius Medical, Sirius Medical, Servier, ClearCut, Laborarztpraxis Walther, Jörg Eickeler, Vifor; Financial Interests, Personal, Invited Speaker, Manuscript support: Amgen; Financial Interests, Personal, Other, Travel expenses and congress support: AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Aurikamed, Gilead Science, Lilly, MSD, Novartis, Pfizer, pfm medical, Seagen; Financial Interests, Personal, Other, Video statement: GSK; Financial Interests, Personal, Other, Congress support and travel expenses: Neodynamics, Pierre Fabre, Sirius Medical; Financial Interests, Personal, Other, writing support: pfm medical; Financial Interests, Personal, Member of Board of Directors: AWOgyn, DGGG; Financial Interests, Institutional, Invited Speaker: AstraZeneca, ClearCut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical, Novo Scientific, Endomag, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Exact Sciences; Non-Financial Interests, Member of Board of Directors: OncoNet Rhein-Main. 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, Paxman, Sidekick, Teva, Veracyte, Viatris; Financial Interests, Personal, Invited Speaker: Aristo, Clovis Oncology, Eisai, Hexal, Palleos, PINK, FOMF, Aurikamed, Pomme Med, medconcept, MCI, Esteve, Wiley, iMEDInstitute, MediSeminar, Medicultus; Financial Interests, Personal, Expert Testimony: Onkowissen; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Invited Speaker: WSG, PINK, BKFZ; Non-Financial Interests, Advisory Role: PINK, Brustkrebs Deutschland e.V., Junge Erwachsene Mit Krebs, AGO Kommission Mamma, AGSMO, DKG, TZM, CCC München, Mammamia. P. Wimberger: Financial Interests, Institutional, Other, Honoraria: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche, Teva, Eisai; Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Lilly, Roche, Teva, Eisai, Clovis, GSK; Financial Interests, Institutional, Funding: Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche, Clovis, GSK. A.D. Hartkopf: Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Agendia, Amgen, Clovis, Daiichi 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, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, GSK, Lilly, Hexal, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen; Financial Interests, Institutional, Funding: Exact 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, Seagan. C. Schem: Financial Interests, Personal, Advisory Board: Roche, Novartis, Lilly, AstraZeneca, Daiichi Sankyo Sanyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, Gilead. M. Zaiss: Financial Interests, Advisory Role: Roche, Janssen, Novartis, AstraZeneca, Gilead, AbbVie; Financial Interests, Speaker’s Bureau: Roche, Pfizer. M.K. Graeser-Mayer: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Other, Travel Expenses: Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Member: West German Study Group. 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: West German Study Group. H. Kreipe: Financial Interests, Other, Honoraria: Roche, Novartis, Genomic Health, AstraZeneca, Lilly, Pfizer; Financial Interests, Advisory Role: Roche, Genomic Health, AstraZeneca. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuellig pharma, 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, Funding: AstraZeneca, BMS, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Palleos, Seagen, TRIO, WSG; 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: Breast Care Journal. All other authors have declared no conflicts of interest.