Background

Intermediate biopsies during neoadjuvant treatment might offer opportunities for prediction of pathological complete response (pCR) and patient outcome, which could be a basis for de-escalation of treatment. However, their relevance for clinical decisions is not clear.

Methods

We evaluated intermediate biopsies that were taken during neoadjuvant treatment from 297 patients with invasive breast cancer from three prospective, randomized trials (GeparQuattro, -Quinto, -Sixto). We evaluated the presence of invasive breast cancer, tumor-infiltrating lymphocytes (TILs) and Ki-67 expression and compared the results to pre-treatment samples. We explored the association of residual cancer in the intermediate biopsies as well as dynamics in Ki-67 and TILs with pCR rates and disease-free survival.

Results

Of the 297 tumors, 87 (29%) samples were triple-negative (TNBC), 138 (46%) HR+/HER2- and 72 (24%) HER2+. We found invasive tumor cells in 70% of biopsies, with significant differences between the subtypes (HR+/HER2-: 84%; TNBC: 62%, HER2+: 51%; p<0.001). In the complete cohort, 8% of patients with invasive tumor cells in intermediate biopsies achieved a pCR after completion of treatment (pCR rate in patients with residual tumor: TNBC: 19%, HR+/HER2: 3%; HER2+: 11%). If no residual cancer was present, pCR rate was 50% in the complete cohort (TNBC: 48%, HR+/HER2-: 27%; HER2+: 66%). An increase in TILs from baseline biopsy to intermediate biopsy was associated with a higher probability of pCR in the overall study cohort (p=0.001). A similar or increased Ki-67 was associated with a low probability of pCR in the overall study cohort (p=0.004) and with a shorter disease-free survival in patients with TNBC (p=0.04).

Conclusions

Intermediate biopsies can identify patients that are unlikely to achieve a pCR after therapy. After further validation, this may be useful for adaptation of treatment. For translational biomarker research, intermediate biopsies are useful tool to study mechanisms of therapy resistance and biomarker discovery. Additional studies will be needed to demonstrate if standardized sampling procedures can further improve response prediction through intermediate biopsies.

Legal entity responsible for the study

German Breast Group.

Funding

Has not received any funding.

Disclosure

M. Untch: Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Amgen GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: AstraZeneca; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: BMS; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Celgene GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Eisai; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Lilly Deutschland; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Lilly Int.; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: MSD Merck; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Myriad Genetics; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Pfizer GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Roche Pharma AG; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Novartis; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Pierre Fabre; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Clovis Oncology; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Seatlle Genetics; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Seagen; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: GSK; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Gilead. T. Karn: Other, Personal, Other, Patent pending: EP18209672. M. van Mackelenbergh: Financial Interests, Institutional, Other, Honoraria: Amgen; Financial Interests, Institutional, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Other, Honoraria: Novartis; Financial Interests, Institutional, Other, Honoraria: Pfizer; Financial Interests, Institutional, Other, Honoraria: Pierre Fabre; Financial Interests, Institutional, Other, Honoraria: Lilly; Financial Interests, Institutional, Other, Honoraria: Genomic Health; Financial Interests, Institutional, Other, Honoraria: Molecular Health; Financial Interests, Institutional, Other, Honoraria: Roche; Financial Interests, Institutional, Other, Honoraria: Gilead; Financial Interests, Institutional, Other, Honoraria: Seagen; Financial Interests, Institutional, Other, Honoraria: GSK. J. Huober: Financial Interests, Personal, Other, personal fees: Gilead; Financial Interests, Personal, Other, personal fees: Seagen; Financial Interests, Personal and Institutional, Research Grant, Grant, personal fees: Lilly; Financial Interests, Personal and Institutional, Research Grant, Grant, Travel, personal fees: Novartis; Financial Interests, Personal, Other, Travel, personal fees, Other: Pfizer; Financial Interests, Personal, Other, Travel, personal fees, Other: Daiichi; Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: AbbVie; Financial Interests, Personal, Other, personal fees: Eisai; Financial Interests, Institutional, Research Grant, Grant: Hexal; Financial Interests, Institutional, Research Grant, Grant, Travel, Other: BMS. W.D. Schmitt: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Funding: Myriad Genetics. F. Marmé: Financial Interests, Personal, Other, Personal Fees: Roche/Genentech; Financial Interests, Personal, Other, Personal Fees: AstraZeneca; Financial Interests, Personal, Other, Personal Fees: Pfizer; Financial Interests, Personal, Other, Personal Fees: Tesaro; Financial Interests, Personal, Other, Personal Fees: Novartis; Financial Interests, Personal, Other, Personal Fees: Amgen; Financial Interests, Personal, Other, Personal Fees: PharmaMar; Financial Interests, Personal, Other, Personal Fees: Genomic Health; Financial Interests, Personal, Other, Personal Fees: CureVac; Financial Interests, Personal, Other, Personal Fees: EISAI; Financial Interests, Personal, Other, Persona Fees: BMS; Financial Interests, Personal, Other, Personal Fees: Clovis Oncology; Financial Interests, Personal, Other, Personal Fees: GSK; Financial Interests, Personal, Other, Personal Fees: MSD; Financial Interests, Personal, Other, Personal Fees: Seagen; Financial Interests, Personal, Other, Personal Fees: Myriad Genetics; Financial Interests, Personal, Other, Personal Fees: Pierre Fabre; Financial Interests, Personal and Institutional, Research Grant, Personal Fees: Gilead/Immunomedics; Financial Interests, Personal, Other, Persona fees: Janssen-Cilag. E. Stickeler: Financial Interests, Personal, Other, personal fees: Roche; Financial Interests, Personal, Other, personal fees: Gilead; Financial Interests, Personal, Other, personal fees: MSD; Financial Interests, Personal, Other, personal fees: Lilly; Financial Interests, Personal, Other, personal fees: Pfizer; Financial Interests, Personal, Other, personal fees: Seagen; Financial Interests, Personal, Other, personal fees: PharmaMar. H. Tesch: Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Novartis; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Roche; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: GSK; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Seagen; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Pfizer; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Lilly; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: AstraZeneca; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Daiichi; Financial Interests, Institutional, Other, Consulting fees, honoraria for lectures, presentations: Exact Science. P.A. Fasching: Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Novartis; Financial Interests, Institutional, Research Grant, Grant, Institutional Funding: BioNTech; Financial Interests, Personal and Institutional, Advisory Board, Advisory Board, Invited Speaker, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Grant, Institutional Funding: Cepheid; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board, Advisory Board: Hexal; Financial Interests, Personal, Advisory Board, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Gilead. A. Schneeweiss: Financial Interests, Personal and Institutional, Research Grant, Research Grant, Travel expenses, Honoraria: BMS; Financial Interests, Personal and Institutional, Research Grant, Research Grant, Expert testimony, Travel expenses, Honoraria: Roche; Financial Interests, Institutional, Research Grant, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant, Research Grant: Molecular Partner; Financial Interests, Personal, Expert Testimony, Expert testimony, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria, Travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Seagen; Financial Interests, Personal, Other, Honoraria: Gilead. V. Müller: Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Amgen; Financial Interests, Personal, Invited Speaker, speaker honoraria: AstraZeneca; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Eisai; Financial Interests, Personal, Invited Speaker, speaker honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: MSD; Financial Interests, Personal and Institutional, Invited Speaker, speaker and consultancy honoraria, Institutional research support: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, speaker and consultancy honoraria, Institutional research support: Roche; Financial Interests, Personal, Invited Speaker, speaker honoraria: Teva; Financial Interests, Personal and Institutional, Invited Speaker, speaker honoraria, Institutional research support: Seagen; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: GSK; Financial Interests, Personal, Invited Speaker, speaker and consultancy honoraria: Gilead; Financial Interests, Personal, Advisory Role, consultancy honoraria: Genomic Health; Financial Interests, Personal, Advisory Role, consultancy honoraria: Hexal; Financial Interests, Personal, Advisory Role, consultancy honoraria: Pierre Fabre; Financial Interests, Personal, Advisory Role, consultancy honoraria: ClinSol; Financial Interests, Personal, Advisory Role, consultancy honoraria: Lilly; Financial Interests, Institutional, Other, Institutional research support: Genentech. S. Loibl: Financial Interests, Institutional, Research Grant, Grant, Other: AbbVie; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Amgen; Financial Interests, Institutional, Research Grant, Grant, Other: AstraZeneca; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Bayer; Financial Interests, Institutional, Advisory Board, honorarium for Ad Boards, Other: BMS; Financial Interests, Institutional, Research Grant, Grant, Other: Celgene; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Eirgenix; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: GSK; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Immunomedics/Gilead; Financial Interests, Institutional, Advisory Board, honorarium for Ad Boards, Other: Lilly; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Merck; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Novartis; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Pfizer; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board & Lecture, Other: Pierre Fabre; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board & Lecture, Other: prIME/Medscape; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Medical Writing, Other: Puma; Financial Interests, Institutional, Advisory Board, honorarium for Lecture, Other: Samsung; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Medical Writing, Other: Seagen; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Boards & Lectures, Medical Writing, Other: Roche; Other, Institutional, Other, Patent Pending, Immunsignature in TNBC: EP14153692.0; Other, Institutional, Other, Patent Pending, Signature for CDK 4/6 Inhibitor: EP21152186.9; Other, Institutional, Other, Patent Issued, Predicting response to an Anti-HER2 containing therapy: EP15702464.7; Other, Institutional, Other, Patent Pending, GeparNuevo: EP19808852.8; Other, Institutional, Royalties, Patent Issued, Royalties, VM Scope GmbH: Digital Ki67 Evaluator. C. Denkert: Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Sividon Diagnostics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: MSD Oncology; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Molecular Health; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Merck; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role, Research Funding: Roche; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Lilly; Financial Interests, Institutional, Research Grant, Research Funding: Myriad Genetics; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: VMScope digital pathology software; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2015114146A1; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2010076322A1; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2020109570A1. All other authors have declared no conflicts of interest.

Background

SASCIA (NCT04595565) is an ongoing phase III study randomising patients (pts) with HER2- BC and residual disease after neoadjuvant chemotherapy (NACT) or hormone receptor (HR)+ with a CPS+EG score ≥3 or 2 and ypN+ after NACT to SG or treatment of physicianś choice (TPC, capecitabine, platinum, observation). We present the results of the pre-planned SIA.

Methods

The analysis was performed after the first 50 randomized pts had completed 4 therapy cycles. Pts were included if they received ≥2 cycles, were observed ≥6 wks or discontinued earlier. Objectives were to assess adverse events (AEs) grade (G) 1-4, G3-4 and compliance (dose reductions, delays, discontinuation) between arms.

Results

At the time of the analysis, 142 pts were randomized, 88 were included in the SIA. 45 pts received SG, 32 capecitabine, 11 were observed. Median age was 46 (24-71) in SG vs 51 (32-74) yrs in TPC arm, median BMI (25.8 (20.0-42.6) vs 23.8 (18.2-35.4) kg/m²), more pts in SG arm had a Ki67>20% (N=29, 64.4% vs N=21, 48.8%); 30 (66.7%) vs 29 (67.4%) were HR-, 15 (33.3%) vs 14 (32.6%) HR+. All pts had AEs G1-4 in SG arm vs 37 (86.0%) in TPC arm, and 30 (66.7%) vs 9 (20.9%) G3-4 (Table), no death occurred. 6 (13.6%) pts under SG vs 3 (9.4%) under capecitabine discontinued therapy prematurely; 30 (66.7%) vs 13 (43.2%) had ≥1 dose delay, due to hematological (N=21, 46.7% vs N=3, 10.0%) and non-hematological AEs (N=3, 6.7% vs N=7, 23.3%); 12 (26.7%) vs 9 (28.1%) had ≥1 dose reduction (hematological N=6, 13.3% vs N=1, 3.1%; non-hematological N=5, 11.1% vs N=6, 18.8%). Table: 58O

Statistically significant different AEs between arms

Conclusions

SG showed a higher rate of AEs compared to TPC, which includes observation only. AEs, especially G3-4 AEs rate were in line with the known safety profile of SG and led to more dose delays. AEs due to SG therapy was well manageable using the recommended supportive measures. The study continues as planned.

Clinical trial identification

NCT04595565.

Legal entity responsible for the study

German Breast Group.

Funding

The trial is financially supported by Gilead Sciences, Inc.

Disclosure

F. Marmé: Financial Interests, Personal and Institutional, Research Grant, Grant, Personal fees: Gilead/Immunomedics; Financial Interests, Personal, Other, Personal fees: Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, Genomic Health, CureVac, Eisai, BMS, Clovis, Janssen-Cilag, GSK, MSD, Seagen, Myriad, Pierre Fabre. C. Hanusch: Financial Interests, Personal, Other, Personal Fees: Roche, Novartis, Lilly, AstraZeneca. T. Link: Financial Interests, Personal, Other: Pfizer, Roche, Tesaro, Amgen, Novartis, Lilly, Myriad, Eisai, Gilead; Non-Financial Interests, Personal, Other: MSD, Clovis, GSK; Non-Financial Interests, Institutional, Other: BMS, Daiichi Sankyo. C. Denkert: Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Sividon Diagnostics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca Merck, Lilly; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role, Research Funding: Roche; Financial Interests, Institutional, Research Grant, Research Funding: Myriad Genetics; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: VMScope Digital Pathology Software, WO2015114146A1, WO2010076322A1, WO2020109570A1. P.A. Fasching: Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Novartis, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Seagen, Roche, Gilead; Financial Interests, Institutional, Research Grant, Grant: BioNTech, Cepheid; Financial Interests, Personal and Institutional, Advisory Board, Advisory Board, Invited Speaker, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board: Pierre Fabre, Hexal, Agendia, Sanofi Aventis. C. Jackisch: Financial Interests, Personal, Other: Roche, AstraZeneca, Pfizer, Lilly, Novartis, Exact Sciences; Financial Interests, Institutional, Other: Seagen. P. Aftimos: Financial Interests, Personal, Other: Boehringer Ingelheim, Macrogenics, Amcure, Synthon, Servier, G1 Therapeutics, Novartis, Radius, Deloitte, Menarini, Gilead; Non-Financial Interests, Personal, Other, Travel Grant: Roche; Non-Financial Interests, Institutional, Other, Travel Grant: Amgen, MSD, Pfizer. J. Huober: Financial Interests, Personal, Other: Gilead, Seagen, Roche, MSD, AbbVie, Eisai; Financial Interests, Personal and Institutional, Research Grant, Grant: Lilly; Financial Interests, Personal and Institutional, Research Grant, Grant, Travel, Other: Novartis; Financial Interests, Personal, Other, Travel, Other: Pfizer, Daiichi; Financial Interests, Institutional, Research Grant, Grant: Hexal; Financial Interests, Institutional, Research Grant, Grant, Travel: BMS. M. Untch: Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Amgen GmbH, AstraZeneca, Celgene GmbH, Daiichi Sankyo, Eisai, Lilly Int., MSD Merck, Myriad Genetics, Pfizer GmbH, Roche Pharma AG, Sanofi Aventis Deutschland GmbH, Novartis, Clovis Oncology; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: BMS, Lilly Deutschland, Pierre Fabre, Seattle Genetics, Seagen, GSK, Gilead. M. Balic: Financial Interests, Institutional, Research Grant, Grants: ABCSG; Financial Interests, Institutional, Research Grant, Grant, Consulting fees, Payment or honoraria for lectures, Support for attending meetings, travel, Data safety board or advisory board: AstraZeneca, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche; Financial Interests, Institutional, Research Grant, Grant, Consulting fees, Payment or honoraria for lectures, Data safety board or advisory board: Daiichi Sankyo, Seagen; Financial Interests, Institutional, Research Grant, Grant, Consulting fees, Payment or honoraria for lectures: Samsung. M. Reinisch: Financial Interests, Personal, Other: AstraZeneca, Novartis, Roche, Pfizer, Somatex, Daiichi Sankyo, Lilly MSD. J. Blohmer: Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Honoraria: Amgen, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Travel, Accommodations, Expenses, Honoraria: Pfizer, Roche; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Lilly, Gilead Sciences, Eisai Germany, Seattle Genetics, Daiichi Sankyo/AstraZeneca, Exact Sciences, Molecular Health. S. Loibl: Financial Interests, Institutional, Research Grant, Grant, Other: AbbVie, AstraZeneca, Celgene; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Amgen, Bayer, BMS; Non-Financial Interests, Institutional, Advisory Board, Honorarium for Ad Board & Lecture, Medical Writing: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board, Other: Eirgenix, GSK, Lilly, Merck; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Immunomedics/Gilead; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Board & Lectures, Medical Writing, Grant, Other: Novartis, Pfizer, Roche; Financial Interests, Institutional, Advisory Board, Honorarium for Ad Board & Lecture, Other: Pierre Fabre, prIME/Medscape; Non-Financial Interests, Institutional, Advisory Board, Honorarium for Ad Board, Medical Writing, Other: Puma, Seagen; Financial Interests, Institutional, Advisory Board, honorarium for Lecture, Other: Samsung; Other, Institutional, Other, Patent Pending: EP14153692.0, EP21152186.9; Other, Institutional, Other, Patent Issued: EP15702464.7; Other, Institutional, Other, Patent Pending, GeparNuevo: EP19808852.8; Other, Institutional, Royalties, Patent Issued, Royalties: Digital Ki67 Evaluator. All other authors have declared no conflicts of interest.

Background

PENELOPE-B is a phase III study investigating the role of PAL + ET vs placebo + ET in HR+, HER2- early BC pts with high risk of relapse after neoadjuvant chemotherapy (NACT). Invasive disease-free survival was not improved with PAL + ET (Loibl JCO 2021). Estradiol (E2), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) values might be influenced by post-NACT PAL. Changes in hormones for pts treated with CDK4/6 inhibitors + ET are not well explored.

Methods

616 pts were premenopausal at baseline (BL, investigator-defined). Pts with serum samples at BL and at least before cycle (C) 7 or at end of treatment (EOT) were considered (N=576). 576 pts provided blood samples at BL, 526 before C7, 541 at EOT. Centrally assessed FSH>12.4 IU/l and E2<52.2 ng/L were defined as postmenopausal; fertile level of AMH as ≥0.22 ng/mL (central lab cut-offs). Analysed subgroups were pre- vs postmenopausal FSH/E2 at BL, age ≤40 vs >40 yrs, gonadotropin-releasing hormone analogue (GnRHa) use vs no.

Results

Median age was 43 (19-56) yrs; 46.8% pts had BMI <25, 53.2% ≥25. Hormone values are shown below. At BL, 41.6% of pts in the placebo vs 41.3% in the PAL arm had premenopausal hormone levels. Of these, 9.1 vs 13.5% (p=0.387) had postmenopausal hormone levels at C7. In pts ≤40 yrs 29.2 vs 29.5% at BL (p=1.000), 18.1 vs 23.4% at C7 (p=0.472) had postmenopausal values. More pts >40 yrs (BL 75.3%, C7 69.8%) vs ≤40 yrs (29.4, 20.7%) and without GnRHa (80.3, 72.2%) vs with (15.9, 12.1%) had postmenopausal hormone levels. Median AMH was under the detection limit at all time points. At BL 91.8 vs 93.6% had non-fertile levels of AMH (p=0.426), 94.4 vs 96.5% at C7 (p=0.298), without difference in subgroups. EOT analysis will be presented at the meeting. Table: 60MO

Conclusions

PAL does not influence FSH, E2 and the ovarian reserve significantly when added to ET after NACT.

Clinical trial identification

NCT01864746.

Legal entity responsible for the study

German Breast Group.

Funding

Funding and drug were provided by Pfizer.

Disclosure

F. Marmé: Financial Interests, Personal, Other, Personal Fees: Roche, AstraZeneca, Pfizer, Tesaro, Novartis, Amgen, PharmaMar, Genomic Health, CureVac, Eisai, BMS, Clovis, Janssen-Cilag, GSK, MSD, Seagen, Myriad, Pierre Fabre; Financial Interests, Personal and Institutional, Research Grant, Grant: Gilead/immunomedics. Y. Liu: Financial Interests, Institutional, Stocks/Shares: Pfizer. M. Martin Jimenez: Financial Interests, Institutional, Research Grant, Grant: Roche; Financial Interests, Institutional, Research Grant, Grant, Consulting/Advisory Fees: Puma; Financial Interests, Institutional, Research Grant, Grant, Consulting/Advisory Fees, Speakers’ Honoraria: Novartis; Financial Interests, Institutional, Advisory Role, consulting/advisory fees, speakers’ honoraria: AstraZeneca, Amgen, Roche, Genentech, Eli Lilly, Pfizer; Financial Interests, Institutional, Advisory Role, consulting/advisory fees: Taiho Oncology, PharmaMar, Daiichi Sankyo. C. Denkert: Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Sividon Diagnostics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: MSD Oncology, Daiichi Sankyo, Molecular Health, AstraZeneca, Merck, Lilly; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role, Research Funding: Roche; Financial Interests, Institutional, Advisory Role, Research Funding: Myriad Genetics; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: VMScope Digital Pathology Software, WO2015114146A1, WO2010076322A1, WO2020109570A1. T. Karn: Other, Personal, Other, Patent pending: EP18209672. M. van Mackelenbergh: Financial Interests, Institutional, Other, Honoraria: Amgen, AstraZeneca, Roche, Pfizer, Novartis, Lilly, Pierre Fabre, Genomic Health, Molecular Health, Gilead, Seagen, GSK. P.A. Fasching: Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Novartis, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Seagen, Roche, Gilead; Financial Interests, Institutional, Research Grant, Grant: BioNTech, Cepheid; Financial Interests, Personal and Institutional, Advisory Board, Advisory Board, Invited Speaker, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board, Advisory Board: Pierre Fabre, Hexal, Agendia, Sanofi Aventis. V. Müller: Financial Interests, Personal, Invited Speaker, Speaker and Consultancy Honoraria: Amgen, Daiichi Sankyo, MSD, GSK, Gilead; Financial Interests, Personal, Invited Speaker, Speaker Honoraria: AstraZeneca, Eisai, Pfizer, Teva; Financial Interests, Personal and Institutional, Invited Speaker, Speaker and Consultancy Honoraria: Novartis, Roche; Financial Interests, Personal and Institutional, Invited Speaker, Speaker Honoraria: Seagen; Financial Interests, Personal, Advisory Role, Consultancy Honoraria: Genomic Health, Hexal, Pierre Fabre, ClinSol, Lilly; Financial Interests, Institutional, Other, Other: Genentech. E. Stickeler: Financial Interests, Personal, Other, Personal Fees: Roche, Gilead, MSD, Lilly, Pfizer, Seagen, PharmaMar. S. Loibl: Financial Interests, Institutional, Research Grant, honorarium for Ad Boards: AbbVie, Celgene; Financial Interests, Institutional, Advisory Board, honorarium for Ad Board: Amgen, Bayer, BMS, Eirgenix, GSK, Lilly, Merck; Financial Interests, Institutional, Research Grant, honorarium for Ad Boards & Lectures, Grant, Other: AstraZeneca; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board & Lecture, Medical Writing: Daiichi Sankyo, Roche; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board, Medical Writing: Immunomedics/Gilead; Non-Financial Interests, Institutional, Research Grant, honorarium for Ad Board, Medical Writing: Novartis, Pfizer; Financial Interests, Institutional, Invited Speaker, honorarium for Ad Board & Lecture: Pierre Fabre, prIME/Medscape; Non-Financial Interests, Institutional, Invited Speaker, honorarium for Ad Board, Medical Writing: Puma; Financial Interests, Institutional, Invited Speaker, honorarium for Lecture: Samsung; Non-Financial Interests, Institutional, Invited Speaker, honorarium for Ad Boards, Medical Writing: Seagen; Other, Institutional, Other, Patent Pending: EP14153692.0, EP21152186.9; Other, Institutional, Other, Patent Issued: EP15702464.7; Other, Institutional, Other, Patent Pending, GeparNuevo: EP19808852.8; Other, Institutional, Royalties, Patent Issued, Royalties: Digital Ki67 Evaluator. All other authors have declared no conflicts of interest.

Background

GeparX (NCT02682693) investigated efficacy and safety of adding Dmab to standard NACT and two different nP schedules for primary BC. Addition of Dmab to NACT did not improve pCR rates. nP weekly (q1w) significantly increased pCR rate compared to d1,8 q3w schedule, but was associated with higher toxicity (Blohmer et al. Cancer Res 2020). Here we present QoL.

Methods

Patients (pts) were randomized to receive or not receive Dmab 120mg s.c. q4w for 6 cycles and to either nP 125mg/m² q1w or d1,8 q3w for 4 cycles, followed by 4x epirubicin/cyclophosphamide (q2w/q3w). QoL was assessed at baseline (BL), after nP, at end of treatment and 90 days (d) post-surgery (PS) using the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane) questionnaire, FACT-Taxane Trial Outcome Index (TOI), FACT-G total score, and FACT-Taxane total score scales. Higher mean scores indicate better functioning and QoL. Mixed models including BL value as a random effect and treatment, time, and treatment by time interaction as fixed effects were used to compare the QoL scores based on the safety set. Primary endpoint was the mean score change from BL to 90d PS.

Results

Between 02/2017 and 03/2019, 780 pts were randomized and started treatment, of whom 768 were eligible for QoL analyses. BL parameters were well balanced. Questionnaire completion response remained >70% throughout the trial. Addition of Dmab did not change the QoL scores at any time point. Pts receiving nP q1w reported significantly lower mean scores of physical/functional well-being and FACT-G total score (p<0.001) compared to pts receiving nP d1,8 q3w. The decreased well-being with nP q1w partly persists 90d PS. The mean scores of additional concerns, FACT-Taxane TOI and FACT-Taxane total scores significantly differed favouring nP d1,8 q3w in all post-BL assessments (p<0.001). Social/family and emotional aspects were not affected by the regime.

Conclusions

nP q1w led to a significantly higher pCR rate but is associated with decreased QoL compared to nP d1,8 q3w, which is consistent with the higher toxicity reported for nP q1w. Benefit and risks need to be discussed with the pts.

Clinical trial identification

NCT02682693.

Legal entity responsible for the study

German Breast Group.

Funding

GeparX was financially supported by Amgen and BMS (Celgene).

Disclosure

M. Reinisch: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Somatex; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: MSD. J. Blohmer: Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Honoraria: Amgen; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Honoraria: Novartis; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Travel, Accommodations, Expenses, Honoraria: Pfizer; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role, Travel, Accommodations, Expenses, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: MSD Oncology; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Gilead Sciences; Financial Interests, Personal, Other, Honoraria: Eisai Germany; Financial Interests, Personal, Other, Honoraria: Seattle Genetics; Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo/AstraZeneca; Financial Interests, Personal, Other, Honoraria: Exact Sciences; Financial Interests, Personal, Other, Honoraria: Molecular Health. T. Link: Financial Interests, Personal, Other, Personal Fees: Pfizer; Financial Interests, Personal, Other, Personal Fees: Roche; Financial Interests, Personal, Other, Personal Fees: Tesaro; Non-Financial Interests, Personal, Other, Personal Fees: MSD; Financial Interests, Personal, Other, Personal Fees: Amgen; Non-Financial Interests, Personal, Other, Personal Fees: Clovis; Non-Financial Interests, Institutional, Other: Celgene; Financial Interests, Personal, Other, Personal Fees: Novartis; Financial Interests, Personal, Other, Personal Fees: Lilly; Non-Financial Interests, Personal, Other, Personal Fees: GSK; Financial Interests, Personal, Other, Personal Fees: Myriad; Financial Interests, Personal, Other, Personal Fees: Eisai; Non-Financial Interests, Institutional, Other: Daiichi Sankyo; Financial Interests, Personal, Other, Personal Fees: Gilead. M. Untch: Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Amgen GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: AstraZeneca; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: BMS; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Celgene GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Daiichi Sankyo; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Eisai; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Lilly Deutschland; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Lilly Int.; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: MSD Merck; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Myriad Genetics; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Pfizer GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Roche Pharma AG; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Novartis; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Pierre Fabre; Non-Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Clovis Oncology; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Seatlle Genetics; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Seagen; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: GSK; Financial Interests, Personal and Institutional, Other, All fees to the institution/employer: Gilead. P.A. Fasching: Financial Interests, Personal, Invited Speaker, Advisory Board, Invited Speaker: Novartis; Financial Interests, Institutional, Funding, Grant, Institutional Funding: BioNTech; Financial Interests, Personal and Institutional, Research Grant, Advisory Board, Invited Speaker, Research Grant: Pfizer; Financial Interests, Personal, Invited Speaker, Advisory Board, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Advisory Board, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker, Advisory Board, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker, Advisory Board, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Institutional Funding: Cepheid; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board, Advisory Board: Hexal; Financial Interests, Personal, Advisory Board, Advisory Board: Agendia; Financial Interests, Personal, Advisory Board, Advisory Board: Sanofi Aventis; Financial Interests, Personal, Advisory Board, Advisory Board, Invited Speaker: Gilead. A. Schneeweiss: Financial Interests, Personal, Research Grant, Research Grant, Travel expenses, Honoraria: BMS; Financial Interests, Personal, Research Grant, Research Grant, Expert testimony, Travel expenses, Honoraria: Roche; Financial Interests, Institutional, Research Grant, Research Grant: AbbVie; Financial Interests, Institutional, Research Grant, Research Grant: Molecular Partner; Financial Interests, Personal, Expert Testimony, Expert testimony, Honoraria: AstraZeneca; Financial Interests, Personal, Other, Honoraria, Travel expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: MSD; Financial Interests, Personal, Other, Honoraria: Tesaro; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Gilead; Financial Interests, Personal, Other, Honoraria: Seagen. P. Wimberger: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Roche Pharma GmbH; Financial Interests, Institutional, Research Grant: GSK. S. Seiler: Financial Interests, Institutional, Research Grant, Grant: Amgen; Financial Interests, Institutional, Research Grant, Grant: BMS; Financial Interests, Personal, Other, Presentations: AbbVie. J. Huober: Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: Seagen; Financial Interests, Personal and Institutional, Research Grant, Grant: Lilly; Financial Interests, Personal and Institutional, Research Grant, Grant, Travel, Other: Novartis; Financial Interests, Personal, Other, Travel, Other: Pfizer; Financial Interests, Personal, Other, Travel, Other: Daiichi; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: AbbVie; Financial Interests, Personal, Other: Eisai; Financial Interests, Institutional, Research Grant, Grant: Hexal; Financial Interests, Institutional, Research Grant, Grant, Travel, Other: BMS. M. Thill: Non-Financial Interests, Personal, Other, Personal Fees: Amgen; Financial Interests, Personal, Other, Personal Fees: AstraZeneca; Non-Financial Interests, Personal, Other, Personal Fees: BMS; Financial Interests, Personal, Other, Personal Fees: Daiichi Sankyo; Financial Interests, Personal, Other, Personal Fees: Eisai; Non-Financial Interests, Personal and Institutional, Research Grant, Trial funding, Grant, Personal Fees: Exact Sciences; Financial Interests, Personal, Other, Personal Fees: Lilly; Financial Interests, Personal, Other, Personal Fees: MSD; Financial Interests, Personal, Other, Personal Fees: Hexal; Financial Interests, Personal, Other, Personal Fees: Novartis; Financial Interests, Personal, Other, Personal Fees: Pfizer; Non-Financial Interests, Personal, Other, Manuscript support, Other: PFM Medical; Non-Financial Interests, Personal, Other, Personal Fees: Roche; Financial Interests, Personal, Other, Personal Fees: Tesaro; Financial Interests, Personal, Other, Manuscript support, Other: Clovis; Financial Interests, Personal, Other, Personal Fees: Seagen; Financial Interests, Institutional, Research Grant, Grant, Trial funding: Endomagnetics; Financial Interests, Personal, Other, Personal Fees: Norgine; Non-Financial Interests, Institutional, Other: RTI Surgical; Non-Financial Interests, Institutional, Other, Manuscript support, Other: Clearcut; Financial Interests, Personal, Other, Personal Fees: Becton and Dickinson; Financial Interests, Personal, Other, Manuscript support, Other: Servier; Financial Interests, Personal, Other, Personal Fees: Gilead Sciences; Financial Interests, Personal, Other, Personal Fees: Sysmex; Non-Financial Interests, Personal, Other, Personal Fees: Neodynamics; Financial Interests, Personal, Other, Personal Fees: GSK; Financial Interests, Personal, Other, Personal Fees: Vifor; Financial Interests, Personal, Other, Personal Fees: Organon; Financial Interests, Personal, Other, Personal Fees: Viatris; Financial Interests, Personal, Other, Manuscript support, Other: Vifor. C. Jackisch: Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Celgene; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Exact Sciences; Financial Interests, Institutional, Other: Seagen. K. Rhiem: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Amgen. C. Hanusch: Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: AstraZeneca. C. Denkert: Financial Interests, Personal, Ownership Interest, Stock and Other Ownership Interests: Sividon Diagnostics; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: MSD Oncology; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Molecular Health; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Merck; Financial Interests, Personal and Institutional, Advisory Role, Consulting or Advisory Role, Research Funding: Roche; Financial Interests, Personal, Advisory Role, Consulting or Advisory Role: Lilly; Financial Interests, Institutional, Funding, Research Funding: Myriad Genetics; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: VMScope digital pathology software; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2015114146A1; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2010076322A1; Other, Personal, Royalties, Patents, Royalties, Other Intellectual Property: WO2020109570A1. S. Loibl: Financial Interests, Institutional, Advisory Board, Grant, Other: AbbVie; Financial Interests, Institutional, Advisory Board, Other: Amgen; Financial Interests, Institutional, Advisory Board, Grant, Other: AstraZeneca; Financial Interests, Institutional, Advisory Board, Other: Bayer; Financial Interests, Institutional, Advisory Board, Other: BMS; Financial Interests, Institutional, Advisory Board, Grant, Other: Celgene; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board, Other: Eirgenix; Financial Interests, Institutional, Advisory Board, Other: GSK; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Immunomedics/Gilead; Financial Interests, Institutional, Advisory Board, Other: Lilly; Financial Interests, Institutional, Advisory Board, Other: Merck; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Novartis; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Pfizer; Financial Interests, Institutional, Advisory Board, Other: Pierre Fabre; Financial Interests, Institutional, Advisory Board, Other: prIME/Medscape; Non-Financial Interests, Institutional, Advisory Board, Medical Writing, Other: Puma; Financial Interests, Institutional, Other, honorarium for Lecture: Samsung; Non-Financial Interests, Institutional, Advisory Board, honorarium for Ad Boards, Medical Writing: Seagen; Non-Financial Interests, Institutional, Research Grant, Grant, Medical Writing, Other: Roche; Other, Institutional, Other, Patent Pending, Immunsignature in TNBC: EP14153692.0; Other, Institutional, Other, Patent Pending, Signature for CDK 4/6 Inhibitor: EP21152186.9; Other, Institutional, Other, Patent Issued, Predicting response to an Anti-HER2 containing therapy: EP15702464.7; Other, Institutional, Other, Patent Pending, GeparNuevo: EP19808852.8; Other, Institutional, Royalties, Patent Issued, Royalties, VM Scope GmbH: Digital Ki67 Evaluator. All other authors have declared no conflicts of interest.

Background

Up to 30% of metastatic breast cancer (BC) patients (pts) develop brain metastases (BM). Prognosis of pts with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities.

Methods

A total of 2889 out of 3234 pts of the BMBC registry were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the survival curve resulting in a cut-off of 15 months. 887 patients were categorized as long-term survivors.

Results

Long-term survivors compared to other pts were younger at BC and BM diagnosis (median 48 vs 54 years and 53 vs 59 years), had more often HER2+ tumors (59.1% vs 36.3%), less frequently luminal-like (29.1% vs 35.7%) or TNBC (11.9% vs 28.1%), showed better ECOG at time of BM diagnosis (ECOG 0-1 76.9% vs 51.0%), higher pCR rate (21.6% vs 13.7%) and lower number of BM (n=1 BM 40.9% vs 25.4%; n=2-3 BM 26.5% vs 26.7%; n≥4 BM 32.6% vs 47.9%) (p<0.001). Long-term survivors had less leptomeningeal metastases (10.4% vs 17.5%) and extracranial metastases (ECM, 73.6% vs 82.5%), and more often asymptomatic BM at time of BM diagnosis (26.5% vs 20.1, p<0.001). Median OS in long-term survivors was 30.9 months (95% CI 28.8-32.6) overall, 33.9 (95% CI 31.5-37.9) in HER2+, 26.9 (95% CI 25.0-30.9) in luminal-like and 26.5 (95% CI 22.7-31.2) in TNBC pts. Factors significantly associated with a categorization of long-term survivors are presented in the table below. Table: 170P

Multivariate logistic regression in long-term vs short-term survivors

Conclusions

Our analysis identified factors associated with long-term survival of BC pts with BM and characterized clinical features of this patient cohort. Pts with better ECOG status, younger age, lower number of BM, less extended visceral metastases are more likely to show a long-term survival and therefore are more eligible for extended local and systemic treatment.

Legal entity responsible for the study

GBG Forschung.

Funding

Partial Funding Daiichi Sankyo Europe.

Disclosure

M. Schmidt: Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Pantarhei; Financial Interests, Personal, Other: BioNTech; Financial Interests, Personal, Other: Genentech; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: MSD. J. Puppe: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Synlab; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Novartis. K. Lübbe: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Eisei; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche. M. Thill: Financial Interests, Personal, Advisory Board: Sysmex; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: RTI Surgical; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: pfm Medical; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Onkowissen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Neodynamics; Financial Interests, Personal, Advisory Board: Norgine; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Gilead Science; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Clovis; Financial Interests, Personal, Advisory Board: ClearCut; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Biom‘Up; Financial Interests, Personal, Advisory Board: Becton/Dickinson; Financial Interests, Personal, Advisory Board: Aurikamed; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Funding: Endomag; Financial Interests, Personal, Funding: Exact Sciences; Financial Interests, Personal, Invited Speaker: Viatris; Financial Interests, Personal, Invited Speaker: Vifor; Financial Interests, Personal, Invited Speaker: Sysmex; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: RTI Surgical; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: pfm Medical; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Omniamed; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Medtronic; Financial Interests, Personal, Invited Speaker: MCI; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Jörg Eickeler; Financial Interests, Personal, Invited Speaker: I-Med-Institute; Financial Interests, Personal, Invited Speaker: Hexal; Financial Interests, Personal, Invited Speaker: Gilead Science; Financial Interests, Personal, Invited Speaker: Exact Sciences; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Connect Medica; Financial Interests, Personal, Invited Speaker: Clovis; Financial Interests, Personal, Invited Speaker: Celgene; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Art Tempi; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other: Clear Cut. C. Denkert: Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Molecular Health; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Ownership Interest, Cofounder and shareholder of Sividon Diagnostics until 2016: Sividon Diagnostic; Financial Interests, Personal, Invited Speaker: VmScope digital pathology software; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Research Grant: Myriad. S. Loibl: Financial Interests, Institutional, Advisory Board, Member: AbbVie; Financial Interests, Institutional, Advisory Board, Member: Amgen; Financial Interests, Institutional, Advisory Board, Member: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board, Member: Bayer; Financial Interests, Institutional, Advisory Board, Member: BMS; Financial Interests, Institutional, Advisory Board, Member: Celgene; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Institutional, Advisory Board: DSI; Financial Interests, Institutional, Invited Speaker: DSI; Financial Interests, Institutional, Advisory Board, Member: EirGenix; Financial Interests, Institutional, Advisory Board, Member: GSK; Financial Interests, Institutional, Invited Speaker: Ipsen; Financial Interests, Institutional, Advisory Board, Member: Lilly; Financial Interests, Institutional, Advisory Board: Merck KG; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board, Member: Novartis; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board, Member: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: prIME/Medscape; Financial Interests, Institutional, Advisory Board, Member: prIME/Medscape; Financial Interests, Institutional, Advisory Board, Member: Puma; Financial Interests, Institutional, Advisory Board, Member: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: Samsung; Financial Interests, Institutional, Advisory Board, Member: Seagen; Financial Interests, Personal, Full or part-time Employment, CEO: GBG Forschungs GmbH; Financial Interests, Institutional, Invited Speaker, Ki67: VM Scope GmbH; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: AbbVie; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, PIPenelope/Padma: Pfizer; Financial Interests, Personal, Other, SC PALOMA3: Pfizer; Financial Interests, Personal, Other, SC SOLAR1: Novartis; Financial Interests, Personal, Other, SC ASCENT: Immunomedics; Financial Interests, Personal, Other, SC HERCLIMB: Seagen; Financial Interests, Personal, Other, SC Katherine: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Funding: Cepheid; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Non-Financial Interests, Principal Investigator, After publication of primary endpoint: PI Aphinity; Non-Financial Interests, Invited Speaker, Executive Board: BIG; Non-Financial Interests, Other, Medical Writing: Amgen; Non-Financial Interests, Other, Medical Writing: AstraZeneca; Non-Financial Interests, Other, Medical Writing: BMS; Non-Financial Interests, Other, Medical Writing: Celgene; Non-Financial Interests, Other, Medical Writing: Daiichi Sankyo; Non-Financial Interests, Other, Medical Writing: Novartis; Non-Financial Interests, Other, Medical Writing: Pfizer; Non-Financial Interests, Other, Medical Writing: Roche; Non-Financial Interests, Member, German Gynaecological Oncology society: AGO; Non-Financial Interests, Member, German Cancer Society: DKG; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member, Chair ESMO Breast; SC: ESMO; Other, EP18209672.7No financial interest, Institutional: Patent; Other, EP21152186.9No financial interest, institutional: Patent; Other, EP15702464.7No financial interest, institutional: Patent. V. Müller: Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: Teva; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Other: Gilead; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: ClinSol; Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Other: Pierre Fabre; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Hexal; Financial Interests, Personal, Other: Genomic Health; Financial Interests, Institutional, Research Grant: Seagen; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis. I. Witzel: Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca. All other authors have declared no conflicts of interest.