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

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.