Suzette Delaloge (Villejuif, France)

Institut Gustave Roussy

Author Of 7 Presentations

Welcome to the ESMO Breast Cancer 2022 and 2022 Award lecture (ID 24)

Welcome to the ESMO Breast Cancer 2022 (ID 479)

Risk based prevention and screening in breast cancer (ID 31)

MyPeBS study (ID 443)

Lecture Time
13:45 - 13:45
Room
Frankfurt Hall
Date
Tue, 03.05.2022
Time
13:45 - 15:15
Poster Display session (ID 9)

135P - Real time genotyping-based breast cancer risk assessment in MyPeBS, an International randomized trial in the general population comparing risk-stratified to standard breast cancer screening (BCS) (ID 148)

Abstract

Background

Risk-stratified BCS, integrating personal, familial variables and a polygenic risk score (PRS) is a promising strategy that may improve current BCS outcomes. Real-time risk assessment and field implementation are some of the main challenges for such an approach.

Methods

MyPeBS is an ongoing EU-funded international randomized trial running in 6 countries. Eligible women (wn) aged 40-70 are randomized 1:1 between continuing standard organized BCS as recommended in their participating country/region and switching to risk-stratified BCS, in which BCS schedule and modalities are adapted to the individual predicted 5-year risk of invasive BC (IBC). Primary endpoint is 4-year incidence of stage 2 and higher BC. Secondary endpoints include PROs. 5-year IBC risk is estimated using the Mammorisk® BCSC-derived or the Tyrer Cuzick risk score and the centrally-determined PRS313 obtained from a saliva sample and calibrated for national BC incidence and age. We aim to describe 1) the feasibility of real-time assessment of BC risk and 2) the characteristics and risk profiles of the participants.

Results

As of Sept. 7, 2021, 16,550 wn had been randomized. 29% were aged <50 (median age 54 (range 40-70), 13% had a previous benign breast biopsy, 40% a mammographic breast density C or D, 19% a 1st degree family history of breast or ovarian cancer; 72% had tertiary education. 36% were estimated at low risk (<1% risk of IBC at 5 years), 29% at average risk, and 35% at high (34%) or very high risk (1%) (>1.67% and >6% risk, respectively). Only 2.5% of DNA extractions were not usable for genotyping, due to DNA concentration or quality; and 98.8% of the eligible DNA samples were successfully genotyped. Median turnover time from saliva sampling to risk result available was 11 weeks despite the COVID pandemic (currently 7 weeks).

Conclusions

Real-time BC risk assessment based on a large set of polymorphisms, family, screening and hormonal history, and breast density is feasible within organized screening programmes. Participants are so far representative of different categories with some over-representation of highly educated participants.

Clinical trial identification

NCT03672331.

Legal entity responsible for the study

Unicancer.

Funding

European Commission and French National Cancer Institute.

Disclosure

S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. D. Keatley: Financial Interests, Personal, Advisory Board: Public Advisory Board of Heealth Data UK. E. Gauthier: Financial Interests, Personal, Stocks/Shares: Predilife; Financial Interests, Personal, Full or part-time Employment: Predilife. S. Michiels: Financial Interests, Personal, Advisory Role: IDDI; Financial Interests, Personal, Advisory Role: Amaris; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sensorion; Financial Interests, Personal, Advisory Role: Biophytis; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Yuhan. All other authors have declared no conflicts of interest.

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Proffered Paper session 2 (ID 8)

161O - VIOLETTE: Randomised Phase 2 Study of Olaparib (ola) + Ceralasertib (cer) or Adavosertib (ada) vs Ola Alone in Patients (pts) With Metastatic Triple-Negative Breast Cancer (mTNBC) (ID 278)

Abstract

Background

Combining DNA damage response (DDR) inhibitors to inhibit multiple DDR pathways may enhance tumour cell death. Preclinical models show synergistic antitumour effects of ola (PARP1 inhibitor) + cer (ATR inhibitor) or ada (WEE1 inhibitor). VIOLETTE (NCT03330847), a phase 2 open-label study, evaluated ola ± cer or ada as 2nd–3rd line in pts with mTNBC.

Methods

Randomisation was stratified within each arm by mutation status (BRCAm, non-BRCAm homologous recombination repair pathway mutations [HRRm], or no HRRm [non-HRRm]) based on a prospective central tumour test and prior platinum therapy. Pts received ola 300 mg BID, 28-d cycle; cer 160 mg d 1–7 + ola 300 mg BID (cer+ola), 28-d cycle; or ada 150 mg BID d 1–3, 8–10 + ola 200 mg BID (ada+ola), 21-d cycle. Primary study endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), safety, and tolerability. Ada+ola was discontinued early due to higher than expected grade ≥3 haematologic toxicity, which limited its interpretation. We focus on cer+ola vs ola. The sponsor stopped VIOLETTE after reviewing BRCAm stratum efficacy data.

Results

Of 273 pts (450 planned; median age: 53 y), 114 received ola, 112 cer+ola, and 47 ada+ola. Primary analyses showed no statistically significant difference in PFS for cer+ola vs ola (BRCAm: n=83; HR 1.02 [90% CI 0.63–1.66, P=0.94], HRRm: n=40; 0.54 [0.28–1.03, 0.13], non-HRRm: n=103; 0.76 [0.50–1.14, 0.30]). No statistically significant difference in ORR was seen for cer+ola vs ola in BRCAm (50% vs 44%) or HRRm (20% vs 15%). ORR was higher in non-HRRm for cer+ola (15%, n=8) vs ola (4%, n=2) (odds ratio 4.45; 90% CI 1.30–21.20, P=0.04). In all pts, nausea and anaemia were the most common adverse events (AEs). Grade ≥3 AEs: 36% ola, 47% cer+ola, 78% ada+ola. Details of exploratory and subgroup analyses will be presented.

Conclusions

Cer+ola did not improve PFS vs ola as 2nd–3rd line for mTNBC. Clinical significance of higher ORR with cer+ola in non-HRRm pts is unclear. Cer+ola had a manageable safety profile consistent with known profiles of each. Further analyses may identify pts likely to benefit from each treatment.

Clinical trial identification

NCT03330847.

Editorial acknowledgement

Medical writing assistance, funded by AstraZeneca, was provided by Anna Frangou, PhD, and Stephan Lindsey, PhD, of Peloton Advantage, LLC, an OPEN Health company, under the direction of the authors.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

A. Tutt: Financial Interests, Personal, Advisory Board, Personal fees /Advisory Board related to targeted therapies in DNA repair deficient: Pfizer; Financial Interests, Personal, Advisory Board, Personal fees from /Advisory Board related to targeted therapies in DNA repair deficient: Vertex; Financial Interests, Personal, Advisory Board, Personal fees/Advisory Board related to targeted therapies in DNA repair deficient: Artios; Financial Interests, Personal, Advisory Board, Personal fees/Advisory Board related to targeted therapies in DNA repair deficient: prIME Oncology; Financial Interests, Personal, Advisory Board, Personal Fees/Moon Shot Breast Cancer Scientific Advisory Board Honoraria: MD Anderson; Financial Interests, Personal, Advisory Board, Personal fees/Scientific Ad Board function and stock options: Inbiomotion; Financial Interests, Personal, Invited Speaker, Speaking role at mini symposium: SABCS 2020; Financial Interests, Personal, Advisory Board, Personal fees relating to advisory board: Gilead 21.05.21; Financial Interests, Institutional, Expert Testimony, CRUK expert panel monies going to my research account at the Institute of Cancer Research/Honoraria associated with Deputy Chair also going into research account: CRUK; Financial Interests, Institutional, Invited Speaker, Paid into research account at the Institute of Cancer Research: AZ Symposium ESMO 2021; Financial Interests, Personal, Advisory Board, Personal fees from Advisory Boards: MERCK Serano; Financial Interests, Institutional, Expert Testimony, Paid into research institute account: GE Healthcare 17.06.21; Financial Interests, Personal, Expert Testimony, Personal fees paid for expert testimony: EM Partners 16.06.21; Financial Interests, Institutional, Invited Speaker, Speaker at round table and monies went into research account: VJ Oncology 11.06.21; Financial Interests, Personal, Expert Testimony, Personal fees for an educational video: Medscape Education; Financial Interests, Personal, Advisory Board, Personal and institution fees for Ad Board: Gilead; Financial Interests, Personal, Full or part-time Employment, Head of Division for Breast Research, Director Breast Cancer Now Research Centre, Honorary Consultant Clinical Oncologist, Royal Marsden Hospital, joint leadership appointment with KCL that is processed through ICR payroll: Institute of Cancer Research; Financial Interests, Personal, Full or part-time Employment, Director of Breast Cancer Now Research Unit, King's College London, Honorary Consultant Clinical Oncologist, Breast Unit, Guy’s and St Thomas’ NHS Foundation Trust, joint leadership appointment with ICR that is processed through ICR payroll: King's College London; Financial Interests, Personal, Stocks/Shares: Inbiomotion; Financial Interests, Personal, Royalties, AstraZeneca with royalties paid to The Institute of Cancer Research (ICr) for the use of PARP inhibitors in DNA deficient cancers, licensee - AstraZeneca. ICR rewards to inventor's payments paid to Andrew Tutt's research accounts at The Institute of Cancer Research and to personal accounts: AstraZeneca; Financial Interests, Institutional, Research Grant, Received research support for TNT trial: Myriad genetics; Financial Interests, Personal and Institutional, Invited Speaker, Financial support to my academic and hospital institutions for costs associated with global academic study chair and local site costs for OlympiA trial/Travel expenses related to any trial related travel. Payments through Breast International Group for trial conduct in Olympic trial and through CRO's for commercial PARP inhibitor trial: AstraZeneca; Financial Interests, Institutional, Research Grant, Local site trial associated with clinical trial DNA: MERCK KGAA; Financial Interests, Institutional, Research Grant, Financial support for research at ICR: Medivation; Non-Financial Interests, Other, Member of Strategy Group: NCRI Strategy Group; Non-Financial Interests, Other, Member of the Committee: ESMO Guidelines Committee; Non-Financial Interests, Officer, Committee Member: ESMO 2023 Scientific Committee; Non-Financial Interests, Institutional, Product Samples, Responsible for care of patients receiving Olaparib on named patient programme in Breast Cancer @ Guy's London: Guy's Hospital; Other, Grant funded to study homologous recombination deficient breast and other cancers, BCN receive payments through AstraZeneca related to PARP inhibitor patents: Breast Cancer Now; Other, Grant funded to study homologous recombination deficient breast and other cancers, CRUK receive payments through AstraZeneca related to PARP inhibitor patents: CRUK. Z. Nowecki: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Sanofi Aventis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Other, Traveler Grant: Roche. R. Szoszkiewicz: Financial Interests, Personal, Principal Investigator: Centrum Medyczne Pratia Poznan. S. Im: Non-Financial Interests, Personal, Advisory Role: AstraZeneca; Non-Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Role: Eisai; Non-Financial Interests, Personal, Advisory Role: GSK; Non-Financial Interests, Personal, Advisory Role: Hanmi; Non-Financial Interests, Personal, Advisory Role: Idience; Non-Financial Interests, Personal, Advisory Role: Lilly; Non-Financial Interests, Personal, Advisory Role: MSD; Non-Financial Interests, Personal, Advisory Role: Pfizer; Non-Financial Interests, Personal, Advisory Role: Novartis; Non-Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Daewoong Pharm; Financial Interests, Institutional, Research Grant: Boryung Pharm; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Roche. H. Arkenau: Financial Interests, Personal, Invited Speaker: Servier; Financial Interests, Personal, Invited Speaker: Guardant; Financial Interests, Personal, Advisory Board: iOnctura; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Institutional, Invited Speaker: multiple small and large Pharma/Biotechs. A. Armstrong: Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Conference Fees: Gilead; Financial Interests, Personal, Other, Conference Fees: MSD; Financial Interests, Institutional, Other, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Spousal Shares: AstraZeneca. W. Jacot: Financial Interests, Institutional, Other, Research Funding: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Other, Personal, Other, Congress Travel Support: AstraZeneca; Other, Personal, Other, Congress Travel Support: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly France; Other, Personal, Other, Congress Travel Support: Lilly France; Financial Interests, Personal, Advisory Board: Eisai; Other, Personal, Invited Speaker, Congress Travel Support: Eisai; Financial Interests, Personal, Advisory Board: BMS; Other, Personal, Other, Congress Travel Support: Chugai Pharma; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Other, Personal, Other, Congress Travel Support: Glaxo Smith Kline; Financial Interests, Personal, Advisory Board: Novartis; Other, Personal, Other, Congress Travel Support: Novartis; Financial Interests, Personal, Advisory Board: MSD; Other, Personal, Other, Congress Travel Support: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Other, Personal, Other, Congress Travel Support: Roche; Financial Interests, Personal, Advisory Board: Rain Pharmaceuticals; Other, Personal, Other, Congress Travel Support: Sanofi Aventis; Financial Interests, Personal, Advisory Board: Seagen. J.H. Kim: Financial Interests, Institutional, Other, Research Funding: Ono Pharma Korea Co., Ltd. M. Webster: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Knight; Financial Interests, Personal, Advisory Role: Gilead; Financial Interests, Personal, Advisory Role: Genomic Health. J. Balmana: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. N. Lukashchuk: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. R. Odegbami, A.B. Loembe, M.W. Drachsler: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. E. Casson: Financial Interests, Personal, Full or part-time Employment, Independent contractor: AstraZeneca. E.J. Dean: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. K. Punie: Financial Interests, Personal, Other, Travel Support: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Institutional, Advisory Board: Gilead Sciences; Financial Interests, Institutional, Invited Speaker: Medscape; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Institutional, Invited Speaker: MundiPharma; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Personal, Other, Travel Support: Pfizer; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Advisory Role: Pierre Fabre; Financial Interests, Personal, Other, Travel Support: Roche; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Advisory Role: Teva; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Advisory Role: Vifor Pharma; Financial Interests, Personal, Other, Travel Support: PharmaMar.

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Mini Oral session 2 (ID 2)

167MO - Association between ER, PR and HER2 levels and outcome under palbociclib (Pal) + aromatase inhibitors (AIs) as first-line therapy for ER+ HER2- metastatic breast cancer (MBC): An exploratory analysis of the PADA-1 trial (ID 15)

Abstract

Background

In 1st-line trials, the relative Progression Free Survival (PFS) benefit of adding CDK4/6 inhibitors to AI was consistent across all subgroups of patients (pts), including those with lower ER expression. However, little is known about the absolute PFS obtained under CDK4/6i and AI in pts with low ER expression and whether PR and HER2 expression impact PFS in this setting.

Methods

PADA-1 is a phase III trial (NCT03079011) testing the clinical utility of ESR1mut detection in blood in ER ≥ 10% HER2- MBC pts receiving 1st- line Pal + AI. We investigated the association of locally-assessed ER (%), PR (%) and HER2 (0,1+,2+) IHC expression on the most recent tumor sample with PFS under Pal + AI.

Results

Of 1017 pts, 12 (1.2%), 34 (3.5%), 181 (18.5%) & 751 (76.8%) had an ER% expression of [10-20%], [21-50%], [51-80%] & [81-100%], respectively. N=249 pts (29.2%), 148 (17.3%), 186 (21.8%) & 270 (31.6%) had a PR% of [0-20%], [21-50%], [51-80%] & [81-100%], respectively (Allred scores will be presented). Available HER2 IHC scores were 0 & 1+/2+ in 357 (54.6%) & 296 (45.4%) pts, respectively. In univariate analysis, after a mFU of 28.1 months and 527 PFS events (51.8%) under Pal + AI, mPFS in pts with [10-50%], [51-80%] & [81-100%] ER IHC were 14.1, 21.6 & 30.1 months, respectively. mPFS in pts with [0-50%], [51-80%] & [81-100%] PR IHC were 20.6, 27.1 and 42.6 months, respectively. Longer PFS were observed in HER2(1/2+) vs (0) MBC (HR=0.79 [0.64;0.98]). In multivariate analysis, aside standard prognostic factors (PS, age, visceral disease, number of metastatic site, DMFI), both ER% and PR% had an independent prognostic impact: each +10% gain in ER% was associated with a reduced 10% risk of PFS event under Pal + AI (HR=0.90, 95%CI [0.84;0.96], p=0.002); each +10% gain in PR% was associated with a reduced 8% risk of PFS event under Pal + AI (HR=0.92, 95%CI [0.90;0.95], p<0.001).

Conclusions

ER and PR IHC % have significant, independent and similar impact on PFS achieved under 1st line by Pal + AI. The 14.1 months absolute mPFS obtained among pts with ER IHC <50% suggests that CDK4/6i + AI remains a good treatment option in this patient population.

Clinical trial identification

NCT03079011.

Legal entity responsible for the study

Unicancer & Arcagy-Gineco.

Funding

Pfizer.

Disclosure

T. De La Motte Rouge: Financial Interests, Personal, Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Personal, Financial Interests, Advisory Board: Clovis Oncology; Financial Interests, Personal, Financial Interests, Advisory Board: GSK; Financial Interests, Institutional, Financial Interests, Advisory Board: MSD; Financial Interests, Personal, Financial Interests, Advisory Board: Mylan; Financial Interests, Personal, Financial Interests, Advisory Board: Pfizer; Financial Interests, Personal, Financial Interests, Advisory Board: Roche; Financial Interests, Personal, Financial Interests, Advisory Board: Tesaro; Financial Interests, Institutional, Financial Interests, Local PI: AstraZeneca; Financial Interests, Institutional, Financial Interests, Local PI: GSK; Financial Interests, Institutional, Financial Interests, Research Grant,: MSD; Financial Interests, Institutional, Financial Interests, Local PI: MSD; Financial Interests, Institutional, Financial Interests, Local PI: Netris Pharma; Financial Interests, Institutional, Financial Interests, Research Grant: Novartis; Financial Interests, Institutional, Financial Interests, Research Grant: Pfizer; Non-Financial Interests, Institutional, Non-Financial Interests, Local PI: Pfizer; Financial Interests, Institutional, Financial Interests, Local PI: Roche; Non-Financial Interests, Institutional, Non-Financial Interests, Principal Investigator: Arcagy; Non-Financial Interests, Non-Financial Interests, Advisory Role: French National Cancer Institute; Non-Financial Interests, Non-Financial Interests, Advisory Role: Unicancer. J. Frenel: Financial Interests, Personal, Other, Consulting fees: Novartis; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Pfizer; Financial Interests, Personal, Other, Consulting fees: Lilly; Financial Interests, Personal, Other, Consulting fees: Clovis Oncology; Financial Interests, Personal, Other, Consulting fees: GSK; Financial Interests, Personal, Other, Consulting fees: Gilead; Financial Interests, Personal, Other, Consulting fees: Daiichi Sankyo; Financial Interests, Personal, Other, Consulting fees: Seagen; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Novartis; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: AstraZeneca; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Pfizer; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Lilly; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Clovis Oncology; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: GSK; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Gilead; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Daiichi Sankyo; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Seagen. A. Hardy-Bessard: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Clovis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Seagen; Financial Interests, Personal, Advisory Role: GSK; Non-Financial Interests, Personal, Advisory Role, Travel/Accommodation/Expenses: Roche. T. Bachelot: Non-Financial Interests, Personal, Non-Financial Interests, Advisory board, travel: Roche; Non-Financial Interests, Personal, Non-Financial Interests, Advisory board, travel: AstraZeneca; Non-Financial Interests, Personal, Non-Financial Interests, Advisory board, travel: Pfizer; Non-Financial Interests, Personal, Financial Interests, Advisory board: Seattle Genetics; Non-Financial Interests, Personal, Non-Financial Interests, Advisory board, travel: Novartis. B. Pistilli: Financial Interests, Personal, Advisory Role: Puma Biotechnology; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Myriad Genetics; Financial Interests, Personal, Advisory Role: Pierre Fabre; Financial Interests, Institutional, Funding: Daiichi; Financial Interests, Institutional, Funding: Puma Biotechnology; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Merus; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Sanofi. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Isis/servier; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Advisory Board: Pierre fabre; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Other, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Other, Steering Committee Member: BMS; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Other, Local PI: Orion; Financial Interests, Institutional, Other, Steering Committee Member: Pfizer; Financial Interests, Institutional, Other, Steering Committee Member: Puma; Financial Interests, Institutional, Other, Steering Committee Member: Roche; Financial Interests, Institutional, Other, Steering Committee Member: Sanofi; Financial Interests, Institutional, Other, Coordinating PI: Taiho; Financial Interests, Institutional, Member of the Board of Directors: SFSPM. L. Deiana: Financial Interests, Personal, Other, board and travel: AstraZeneca; Financial Interests, Personal, Other, board and travel: Pfizer; Financial Interests, Personal, Other, board and travel: Lilly; Financial Interests, Personal, Other, board and travel: Novartis. F. Del Piano: Financial Interests, Institutional, Other: Novartis; Financial Interests, Institutional, Other: Daiichi Sankyo. D. Genet: Personal, Other: Pfizer. C.B. Levache: Financial Interests, Institutional, Other, Material disposal: Amgen. F.C. Bidard: Financial Interests, Personal and Institutional, Invited Speaker, and advisory board, research grant, principal investigator: AstraZeneca; Financial Interests, Personal, Advisory Board: BioNTech; Financial Interests, Personal, Invited Speaker, and advisory board: Lilly; Financial Interests, Personal, Advisory Board, and advisory board, research grant, principal investigator: Menarini; Financial Interests, Personal and Institutional, Invited Speaker: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, advisory board, research grant, principal investigator: Pfizer; Non-Financial Interests, Institutional, Advisory Board, and principal investigator: Prolynx; Financial Interests, Personal, Advisory Board, and principal investigator: Radius; Financial Interests, Personal and Institutional, Invited Speaker, and advisory board, research grant: Roche; Financial Interests, Institutional, Invited Speaker, and principal investigator: Sanofi. All other authors have declared no conflicts of interest.

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Poster Display session (ID 9)

174P - Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real world setting: Phase 3b LUCY final analysis (ID 182)

Abstract

Background

LUCY interim findings confirmed the clinical effectiveness of olaparib 300 mg twice daily in patients with metastatic breast cancer (mBC) in a real world setting. Findings were consistent with the OlympiAD trial of olaparib vs chemotherapy of physician’s choice. We report results of the final planned analysis.

Methods

Eligible adults had germline (g) or somatic (s) BRCA1- and/or BRCA2-mutated (BRCAm), HER2-negative mBC and had received taxane and/or anthracycline in early or metastatic settings and ≤2 previous lines of chemotherapy for mBC. Pts with hormone receptor-positive (HR+) mBC had previously completed ≥1 line of endocrine therapy (ET) in any setting or were unsuitable for further ET. Primary endpoint: investigator-assessed progression-free survival (PFS; gBRCAm cohort). Overall survival (OS) and safety were secondary endpoints. Final analysis was planned at 130 OS events (gBRCAm). Results are in all pts (gBRCAm and sBRCAm). Prespecified subgroups (gBRCAm only): HR status (HR+ vs triple-negative breast cancer [TNBC]); line of therapy (1st line vs 2nd line+).

Results

During 2018, 255 pts were enrolled (252 gBRCAm, 3 sBRCAm; median [m] age: 45.0 [range 22–75] years; 98.4% female). mPFS: 8.2 months (95% CI 7.0–9.2; 208 events, 81.6%). mOS: 24.9 months (95% CI 21.1–27.9; 142 events, 55.7%). OS rate at 30 months: 41.7% (95% CI 35.2–48.1). Treatment-related adverse events (AEs, >10% pts): nausea (47.8%), anaemia (34.5%), asthenia (20.8%), fatigue (18.0%), vomiting (17.6%), neutropenia (15.3%) and diarrhoea (11.0%). Grade ≥3 AEs (17.6% pts) included anaemia (11.8%). Few pts (4.3%) discontinued treatment due to an AE. Post study therapies will be reported.

Conclusions

The benefit of olaparib was similar across HR status and treatment lines. mOS was longer than reported in OlympiAD. No new safety signals were observed. These results strongly support olaparib as a chemotherapy-free alternative for gBRCAm, HER2-negative mBC.

Subgroup analyses (full analysis set)

HR status Line of therapy
HER2-negative HER2-negative 1st line 2nd line+
HR+ TNBC
n 134 118 136 116
PFS
Events, n (%) 113 (84.3) 94 (79.7) 107 (78.7) 100 (86.2)
Median 8.38 6.87 8.38 7.59
95% CI 7.92, 10.55 5.52, 9.17 7.20, 10.28 5.88, 9.07
OS
Events, n (%) 73 (54.5) 67 (56.8) 71 (52.2) 69 (59.5)
Median 27.43 21.06 27.43 22.74
95% CI 22.74, 33.45 17.05, 27.30 21.36, 37.42 18.04, 27.20

Editorial acknowledgement

Medical writing assistance was provided by Elizabeth Gandhi, PhD of PharmaGenesis Cambridge, Cambridge, UK, with funding from AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Legal entity responsible for the study

AstraZeneca.

Funding

This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J. Balmana: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MedSir. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Hecal; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BioNTech; Financial Interests, Institutional, Invited Speaker: Cepheid; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: Arbeitsgemeinschaft für Gynäkologische Onkologie e.V.; Non-Financial Interests, Member: Translational Research in Oncology; Non-Financial Interests, Member: Deutsche Gesellschaft für Senologie e.v. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/Servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Other, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Other, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Research Grant: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Other, Research Grant: MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Pfizer; Non-Financial Interests, Principal Investigator: Novartis; Non-Financial Interests, Principal Investigator: MSD; Non-Financial Interests, Principal Investigator: Lilly; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Principal Investigator: Daiichi Sankyo. J. Sohn: Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim. S. Aksoy: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Merck, Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche. C.V. Timcheva: Financial Interests, Personal, Invited Speaker, Presentation during national scientific conference: Roche Bulgaria; Financial Interests, Personal, Advisory Board, Discussion on the place of CDK4/6 inhibitors in the treatment of metastatic breast cancer: Eli Lilly; Financial Interests, Personal, Advisory Board, The role of PARP inhibitors in the treatment of breast and ovarian cancer: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, PI for several clinical trials performing in the hospital: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, PI for several clinical trials performing in the hospital: Parexel; Financial Interests, Personal and Institutional, Invited Speaker, Pi for several clinical trials perforing in the hospital: Roche; Financial Interests, Personal and Institutional, Invited Speaker, PI for some clinical trials performing in the hospital: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, PI for the clinical trial performing in the hospital: I3Research; Non-Financial Interests, Principal Investigator, Investigator initiated trial on metastatic CRC: Merck; Non-Financial Interests, Member, Created in 2012, Head of BAMO until 2020: Bulgarian Association for Medical Oncology (BAMO). T. Park-Simon: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pizer; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis. E. John: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca. K. Baria: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G. Walker: Financial Interests, Institutional, Other, I work as a consultant to the company: AstraZeneca. K.A. Gelmon: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Ayala; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: BMS. All other authors have declared no conflicts of interest.

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Poster Display session (ID 9)

225P - Impact of potential drug-drug interactions (PDDI) on adherence to endocrine therapy (ET) among patients with breast cancer (BC) in the Health Improvement Network (THIN) (ID 235)

Abstract

Background

ET represents a cornerstone in the treatment of early and late hormone receptors-positive (HR+) BC. However, adherence to ET is a major issue that can substantially impact survival outcomes. We explored whether PDDI with ET impact adherence.

Methods

We scanned the French version of the THIN™ database for women who had a reported diagnosis of BC and received ET (tamoxifen [tam] or aromatase inhibitor [AI]) between 1994 and 2021. Adherence was measured annually and defined by a medication possession ratio (MPR) ≥ 80% over 1-year prescription period. PDDI was classified using the Claude Bernard Drug Database into absent, minor (combination to take into account), moderate (combination requiring precautions for use), major (combination not recommended) and contraindicated. We used repeated-measure regression models to estimate odds ratios (OR) for the correlation between MPR ≥ 80% and age, baseline comorbidities, PDDI, and MPR during the previous year. Among patients with multiple PDDI, the worse PDDI category by patient was retained and included in the multivariable model.

Results

Among the 10,863 eligible pts, polypharmacy ≥ 5 drugs was reported in 33.7% and 47.8% of the tam and AI cohorts. PDDI occurrence is summarized in the table. PDDI were mostly moderate in the tam (60.4-80.6%) and AI (94.7%-99.3%) cohorts; contraindicated combinations were below 1%. In the tam cohort, annual MPR ≥ 80% was 79.3% (n = 2,824) at year 1 and 89.5% (n = 426) at year 5. The association between MPR ≥ 80% and presence of PDDI was not statistically significant neither in the tam (OR 0.991, 95% CI 0.0.914-1.075) nor AI (OR 1.046, 95% CI 0.954-1.147) cohorts.

Prevalence of PDDI with ET at baseline and during follow up

Tam AI
PDDI at baseline 13.5% 8.0%
PDDI at year 1 42.4% 31.8%
PDDI at year 2 40.9% 31.4%
PDDI at year 3 40.9% 32.8%
PDDI at year 4 35.5% 32.8%
PDDI at year 5 33.9% 32.5%

Conclusions

Adherence to ET was not associated with PDDI in patients with HR+ BC treated with tam or AI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A. Bardet: Financial Interests, Personal, Other: Roche SAS. O. Bougacha, L. Gantzer, B. Lekens: Financial Interests, Full or part-time Employment: Cegedim R&D. I.V. Luis: Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: Pfizer/Edimark; Financial Interests, Institutional, Invited Speaker: AstraZeneca. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Pierre Fabre, Orion, Sanofi, Rappta, Cellectis, Isis/Servier; Financial Interests, Institutional, Invited Speaker: Exact Sciences, Pfizer, Seagen, Lilly, AstraZeneca, MSD, Roche Genentech, BMS, Puma, Orion, Sanofi; Financial Interests, Institutional, Advisory Board, Ad Board: Besins Healthcare; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker, Clinical Research Funding to my Institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. F. André: Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi; Other, Founder: Pegacsy. S. Michiels: Financial Interests, Personal, Other, Statistical advice: IDDI, Amaris, Roche; Financial Interests, Personal, Other, DSMB member: Sensorion, Servier, Biophytis, Yuhan. B. Pistilli: Financial Interests, Institutional, Advisory Role: AstraZeneca, Pfizer, Novartis, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Myriad, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Novartis, Puma; Financial Interests, Personal, Sponsor/Funding: AstraZeneca, Pierre Fabre, MSD. All other authors have declared no conflicts of interest.

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Presenter Of 3 Presentations

Risk based prevention and screening in breast cancer (ID 31)

MyPeBS study (ID 443)

Lecture Time
13:45 - 13:45
Room
Frankfurt Hall
Date
Tue, 03.05.2022
Time
13:45 - 15:15
Poster Display session (ID 9)

135P - Real time genotyping-based breast cancer risk assessment in MyPeBS, an International randomized trial in the general population comparing risk-stratified to standard breast cancer screening (BCS) (ID 148)

Abstract

Background

Risk-stratified BCS, integrating personal, familial variables and a polygenic risk score (PRS) is a promising strategy that may improve current BCS outcomes. Real-time risk assessment and field implementation are some of the main challenges for such an approach.

Methods

MyPeBS is an ongoing EU-funded international randomized trial running in 6 countries. Eligible women (wn) aged 40-70 are randomized 1:1 between continuing standard organized BCS as recommended in their participating country/region and switching to risk-stratified BCS, in which BCS schedule and modalities are adapted to the individual predicted 5-year risk of invasive BC (IBC). Primary endpoint is 4-year incidence of stage 2 and higher BC. Secondary endpoints include PROs. 5-year IBC risk is estimated using the Mammorisk® BCSC-derived or the Tyrer Cuzick risk score and the centrally-determined PRS313 obtained from a saliva sample and calibrated for national BC incidence and age. We aim to describe 1) the feasibility of real-time assessment of BC risk and 2) the characteristics and risk profiles of the participants.

Results

As of Sept. 7, 2021, 16,550 wn had been randomized. 29% were aged <50 (median age 54 (range 40-70), 13% had a previous benign breast biopsy, 40% a mammographic breast density C or D, 19% a 1st degree family history of breast or ovarian cancer; 72% had tertiary education. 36% were estimated at low risk (<1% risk of IBC at 5 years), 29% at average risk, and 35% at high (34%) or very high risk (1%) (>1.67% and >6% risk, respectively). Only 2.5% of DNA extractions were not usable for genotyping, due to DNA concentration or quality; and 98.8% of the eligible DNA samples were successfully genotyped. Median turnover time from saliva sampling to risk result available was 11 weeks despite the COVID pandemic (currently 7 weeks).

Conclusions

Real-time BC risk assessment based on a large set of polymorphisms, family, screening and hormonal history, and breast density is feasible within organized screening programmes. Participants are so far representative of different categories with some over-representation of highly educated participants.

Clinical trial identification

NCT03672331.

Legal entity responsible for the study

Unicancer.

Funding

European Commission and French National Cancer Institute.

Disclosure

S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. D. Keatley: Financial Interests, Personal, Advisory Board: Public Advisory Board of Heealth Data UK. E. Gauthier: Financial Interests, Personal, Stocks/Shares: Predilife; Financial Interests, Personal, Full or part-time Employment: Predilife. S. Michiels: Financial Interests, Personal, Advisory Role: IDDI; Financial Interests, Personal, Advisory Role: Amaris; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Sensorion; Financial Interests, Personal, Advisory Role: Biophytis; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Advisory Role: Yuhan. All other authors have declared no conflicts of interest.

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Poster Display session (ID 9)

174P - Clinical effectiveness and safety of olaparib in BRCA-mutated, HER2-negative metastatic breast cancer in a real world setting: Phase 3b LUCY final analysis (ID 182)

Abstract

Background

LUCY interim findings confirmed the clinical effectiveness of olaparib 300 mg twice daily in patients with metastatic breast cancer (mBC) in a real world setting. Findings were consistent with the OlympiAD trial of olaparib vs chemotherapy of physician’s choice. We report results of the final planned analysis.

Methods

Eligible adults had germline (g) or somatic (s) BRCA1- and/or BRCA2-mutated (BRCAm), HER2-negative mBC and had received taxane and/or anthracycline in early or metastatic settings and ≤2 previous lines of chemotherapy for mBC. Pts with hormone receptor-positive (HR+) mBC had previously completed ≥1 line of endocrine therapy (ET) in any setting or were unsuitable for further ET. Primary endpoint: investigator-assessed progression-free survival (PFS; gBRCAm cohort). Overall survival (OS) and safety were secondary endpoints. Final analysis was planned at 130 OS events (gBRCAm). Results are in all pts (gBRCAm and sBRCAm). Prespecified subgroups (gBRCAm only): HR status (HR+ vs triple-negative breast cancer [TNBC]); line of therapy (1st line vs 2nd line+).

Results

During 2018, 255 pts were enrolled (252 gBRCAm, 3 sBRCAm; median [m] age: 45.0 [range 22–75] years; 98.4% female). mPFS: 8.2 months (95% CI 7.0–9.2; 208 events, 81.6%). mOS: 24.9 months (95% CI 21.1–27.9; 142 events, 55.7%). OS rate at 30 months: 41.7% (95% CI 35.2–48.1). Treatment-related adverse events (AEs, >10% pts): nausea (47.8%), anaemia (34.5%), asthenia (20.8%), fatigue (18.0%), vomiting (17.6%), neutropenia (15.3%) and diarrhoea (11.0%). Grade ≥3 AEs (17.6% pts) included anaemia (11.8%). Few pts (4.3%) discontinued treatment due to an AE. Post study therapies will be reported.

Conclusions

The benefit of olaparib was similar across HR status and treatment lines. mOS was longer than reported in OlympiAD. No new safety signals were observed. These results strongly support olaparib as a chemotherapy-free alternative for gBRCAm, HER2-negative mBC.

Subgroup analyses (full analysis set)

HR status Line of therapy
HER2-negative HER2-negative 1st line 2nd line+
HR+ TNBC
n 134 118 136 116
PFS
Events, n (%) 113 (84.3) 94 (79.7) 107 (78.7) 100 (86.2)
Median 8.38 6.87 8.38 7.59
95% CI 7.92, 10.55 5.52, 9.17 7.20, 10.28 5.88, 9.07
OS
Events, n (%) 73 (54.5) 67 (56.8) 71 (52.2) 69 (59.5)
Median 27.43 21.06 27.43 22.74
95% CI 22.74, 33.45 17.05, 27.30 21.36, 37.42 18.04, 27.20

Editorial acknowledgement

Medical writing assistance was provided by Elizabeth Gandhi, PhD of PharmaGenesis Cambridge, Cambridge, UK, with funding from AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Legal entity responsible for the study

AstraZeneca.

Funding

This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

J. Balmana: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MedSir. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Hecal; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Agendia; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Invited Speaker: BioNTech; Financial Interests, Institutional, Invited Speaker: Cepheid; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Member: Arbeitsgemeinschaft für Gynäkologische Onkologie e.V.; Non-Financial Interests, Member: Translational Research in Oncology; Non-Financial Interests, Member: Deutsche Gesellschaft für Senologie e.v. S. Delaloge: Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Exact Sciences; Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Advisory Board: Rappta; Financial Interests, Institutional, Advisory Board: Cellectis; Financial Interests, Institutional, Advisory Board: Isis/Servier; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Seagen; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board, ad board: Besins Healthcare; Financial Interests, Institutional, Invited Speaker: Roche Genentech; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Invited Speaker: Puma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Orion; Financial Interests, Institutional, Invited Speaker: Sanofi; Financial Interests, Institutional, Funding: GE; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker, clinical research funding to my institution: Taiho; Non-Financial Interests, Invited Speaker, Société Française de Sénologie et Pathologie Mammaire: SFSPM. Y.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Other, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Other, Research Grant: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Research Grant: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Institutional, Other, Research Grant: MSD; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Non-Financial Interests, Principal Investigator: AstraZeneca; Non-Financial Interests, Principal Investigator: Pfizer; Non-Financial Interests, Principal Investigator: Novartis; Non-Financial Interests, Principal Investigator: MSD; Non-Financial Interests, Principal Investigator: Lilly; Non-Financial Interests, Principal Investigator: Roche; Non-Financial Interests, Principal Investigator: Daiichi Sankyo. J. Sohn: Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim. S. Aksoy: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Merck, Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche. C.V. Timcheva: Financial Interests, Personal, Invited Speaker, Presentation during national scientific conference: Roche Bulgaria; Financial Interests, Personal, Advisory Board, Discussion on the place of CDK4/6 inhibitors in the treatment of metastatic breast cancer: Eli Lilly; Financial Interests, Personal, Advisory Board, The role of PARP inhibitors in the treatment of breast and ovarian cancer: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, PI for several clinical trials performing in the hospital: AstraZeneca; Financial Interests, Personal and Institutional, Invited Speaker, PI for several clinical trials performing in the hospital: Parexel; Financial Interests, Personal and Institutional, Invited Speaker, Pi for several clinical trials perforing in the hospital: Roche; Financial Interests, Personal and Institutional, Invited Speaker, PI for some clinical trials performing in the hospital: Novartis; Financial Interests, Personal and Institutional, Invited Speaker, PI for the clinical trial performing in the hospital: I3Research; Non-Financial Interests, Principal Investigator, Investigator initiated trial on metastatic CRC: Merck; Non-Financial Interests, Member, Created in 2012, Head of BAMO until 2020: Bulgarian Association for Medical Oncology (BAMO). T. Park-Simon: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pizer; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Advisory Board: Exact Sciences; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis. E. John: Financial Interests, Institutional, Full or part-time Employment: AstraZeneca. K. Baria: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G. Walker: Financial Interests, Institutional, Other, I work as a consultant to the company: AstraZeneca. K.A. Gelmon: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Advisory Board: Ayala; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: BMS. All other authors have declared no conflicts of interest.

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Moderator Of 4 Sessions

Berlin Hall Opening and Award lecture
Cologne Hall Special session
Date
Wed, 04.05.2022
Time
11:35 - 12:20
Room
Cologne Hall
Session Type
Special session
Berlin Hall Proffered Paper session
Date
Wed, 04.05.2022
Time
16:45 - 18:15
Room
Berlin Hall
Session Type
Proffered Paper session