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

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

The surgical staging procedure of the axilla in patients who convert from clinically positive (cN+) to clinically negative node status (ycN0) through neoadjuvant chemotherapy is still controversial. Different techniques such as Axillary Lymph Node Dissection (ALND), Targeted Axillary Dissection (TAD), Target Lymph Node Biopsy (TLNB) and Sentinel Lymph Node Biopsy (SLNB) are recommended by the national and international guidelines. In case of TAD and TLNB, the target lymph node can be marked using such markers as clip/coil, carbon ink, magnetic or radioactive seed, or a radar or radiofrequency marker. The AXSANA study is aiming to compare outcomes and morbidity rates between different techniques and will hopefully contribute to defining the optimal axillary staging procedure resulting in high oncological safety and improved quality of life.

Methods

AXSANA is an international prospective, non-interventional cohort study including patients clinically node-positive and scheduled to receive neoadjuvant chemotherapy. The surgical staging procedure is performed according to the standard at their treating institution.

Results

So far, 1,524 patients from 19 countries were recruited and 68% converted to ycN0 status after NACT. In 53% of patients, the planned surgical staging procedure was TAD, followed by ALND (30%), SLNB (15%) and TLNB (2%). In 55% of enrolled patients, at least one node was marked before NACT, mostly using clips/coils (81%), carbon ink (10%), magnetic seeds (8%) and radar markers (1%).

Conclusions

The preliminary data show a strong heterogeneity regarding axillary staging among participating countries. After only 20 months of recruitment, over half of the target accrual (3,000 patients) has been reached. TAD is a widely used technique, but ALND and SLNB are also common. The results of the AXSANA study will clarify whether de-escalation of axillary surgery is a safe option for patients converting from cN+ to ycN0 through neoadjuvant chemotherapy.

Clinical trial identification

NCT04373655.

Editorial acknowledgement

Dr. Rosa Dr Micco; San Raffaele Hospital Milan, Milan, Italy Ellen Schlichting, MD, PhD; Department for Breast and Endocrine Surgery, Oslo University Hospital, Oslo, Norway Dr. Lia Pamela Rebaza, Unit of Basic and Transnational Reseach, Oncosalud-AUNA Clinic, Lima, Perus Dr. Petr V. Krivorotko, Department of Breast Surgical Oncology, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia David Pinto, MD; Breast Unit, Champalimaud Clinical Center, Campalimaud Foundation, Lisbon, Portugal Prof. Florentia Peintinger, Medical University of Graz, Graz. Austria Dr. Maria Luisa Gasparri, Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale, Ospedale Regionale di Lugano, Lugano, Switzerland and University of the Italian Switzerland (USI), Faculty of Biomedicine, Lugano, Switzerland Dr. Hagigat Valiyeva; Oncology Clinc of Azerbaijan Medical University, Baku, Azerbaijan Lukas Dostalek, MD Gynecologic Oncology Center, Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic Dr. Helidon Nina; University Medical Center \"Mother Teresa\", Tirana, Albania Dr. Semra Gunay; Ministry of Health Istanbul Provincal Health Directorate Prof. Dr. Cemil Tascioglu City Hospital, Turkey Dr. Meryem Gunay Gurleyik, Ministry of Health Istanbul Provincial Helath Directorate Istanbul Haydarpasa Numune Research and Training Hospita, Turkey Dr. Elisabeth Thiemann, Brustzentrum Osnabrück, Niels-Stensen-Kliniken, Osnabrück, Germany Dr. Gabriele Kaltenecker, Department of Obstetrics and Gynecology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany.

Legal entity responsible for the study

EUBREAST.

Funding

AGO-B, AWOgyn e.V., Claudia von Schilling Foundation for Breast Cancer Research, Ehmann-Stiftung, Endomag, Merit Medical and Mammotome.

Disclosure

M. Thill: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Aurikamed; Financial Interests, Institutional, Advisory Board: Becton/Dickinson; Financial Interests, Institutional, Advisory Board: Biom'Up; Financial Interests, Institutional, Advisory Board: Celgene; Financial Interests, Institutional, Advisory Board: ClearCut; Financial Interests, Institutional, Advisory Board: Clovis; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Eisai; Financial Interests, Institutional, Advisory Board: Exact Sciences; Financial Interests, Institutional, Advisory Board: Gilead Science; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Norgine; Financial Interests, Institutional, Advisory Board: Neodynamics; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Onkowissen; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: pff Medical; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: RTI Surgical; Financial Interests, Institutional, Advisory Board: Seagen; Financial Interests, Institutional, Advisory Board: Sysmex; Financial Interests, Institutional, Writing Engagements: Servier; Financial Interests, Personal and Institutional, Invited Speaker: Art Tempi; Financial Interests, Personal and Institutional, Invited Speaker: Connect Medica; Financial Interests, Personal and Institutional, Invited Speaker: Hexal; Financial Interests, Personal and Institutional, Invited Speaker: I-Med-Institute; Financial Interests, Personal and Institutional, Invited Speaker: Medtronic; Financial Interests, Personal and Institutional, Invited Speaker: Omniamed; Financial Interests, Institutional, Funding: Endomag; Financial Interests, Institutional, Funding: Exact Science. M.P. Lux: Financial Interests, Institutional, Advisory Board: SamanTree; Financial Interests, Institutional, Advisory Board: PFM; Financial Interests, Institutional, Advisory Board: Sysmex/Endomag. M. Banys- Paluchowski: Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: pfm; Financial Interests, Institutional, Advisory Board: Gilead; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: Seagen. All other authors have declared no conflicts of interest.