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

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.