Background

The MONALEESA-3 (NCT02422615) final protocol-specified OS analysis and an exploratory OS analysis with extended follow-up demonstrated significant OS benefit with RIB + FUL vs placebo (PBO) + FUL as 1L or second-line (2L) treatment (tx). At the time of these analyses, the median (m) OS was 53.7 vs 41.5 mo for RIB vs PBO in the intent-to-treat (ITT) population. Although the mOS was not reached in the RIB arm for 1L pts, the mOS in 2L pts was 39.7 vs 33.7 mo for RIB vs PBO. We report an exploratory analysis of OS with additional follow-up, allowing further characterization of long-term OS benefits of RIB in the 1L setting.

Methods

Postmenopausal pts with HR+/HER2− ABC were randomized 2:1 to receive RIB + FUL or PBO + FUL. Updated OS in the 1L setting (pts with de novo disease or relapse >12 mo from completion of [neo]adjuvant endocrine therapy) was assessed by Cox proportional hazards model and Kaplan-Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were also evaluated.

Results

At the data cutoff (January 12, 2022), the median follow-up for 1L pts was 70.8 mo; 16.5% and 8.6% of pts remained on tx in the RIB and PBO arms, respectively. An OS benefit was observed with 1L RIB vs PBO (mOS, 67.6 vs 51.8 mo; HR, 0.67; 95% CI, 0.50-0.90). The OS rate at 5 years was 56.5% vs 42.1% for RIB vs PBO, respectively. PFS2 (HR, 0.64) and CFS (HR, 0.62) favored RIB vs PBO. In pts who discontinued study tx, 81.8% and 89.7% received subsequent antineoplastic therapy, while 16.7% vs 35.0% received a subsequent cyclin-dependent kinase 4/6 inhibitor in the RIB vs PBO arms. Results in the ITT and 2L populations were generally consistent with the previous analysis.

Conclusions

This exploratory analysis of 1L RIB + FUL in MONALEESA-3 reports the longest mOS thus far (67.6 mo—a 15.8-mo improvement vs PBO and a relative reduction in risk of death of 33%) in a 1L population in a Phase III clinical trial in ABC. These impressive results in the 1L setting further support the use of RIB + ET in HR+/HER2− ABC.

Clinical trial identification

NCT02422615.

Editorial acknowledgement

Medical writing support was provided by Casey Nielsen at MediTech Media, funded by Novartis Pharmaceuticals Corporation.

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.

Funding

Novartis Pharmaceuticals Corporation.

Disclosure

P.A. Fasching: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Seagen, Roche, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Institutional, Funding, Institutional Funding: Biontech, Cepheid; Financial Interests, Personal, Research Grant: Pfizer. S. Chia: Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Hoffman La Roche, Eli Lilly; Financial Interests, Institutional, Funding, My institution received funds for participation in clinical trials by: Novartis, Pfizer, Hoffman La Roche, Eli Lilly. G. Jerusalem: Financial Interests, Personal, Other, Grants, Personal Fees & Non-Financial Support: Novartis, Roche, Pfizer; Financial Interests, Personal, Other, Personal Fees & Non-Financial Support: Lilly, Amgen, BMS, AstraZeneca; Financial Interests, Personal, Other, Personal Fees: AbbVie, Daiichi Sankyo, Seagen; Non-Financial Interests, Personal, Other, Non-Financial Support: Medimmune, Merck KGaA. M. De Laurentiis: Financial Interests, Personal, Speaker’s Bureau, Speaker's Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board Honoraria: Pfizer, Novartis, Roche, AstraZeneca, Eisai, Eli Lilly, MSD, Pierre Fabre. S. Im: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Pfizer, Novartis; Non-Financial Interests, Personal, Other, Travel support: Novartis; Financial Interests, Personal, Advisory Role, Participation in advisory meetings: Eisai, Amgen, Roche, Lilly, GSK, MSD; Financial Interests, Personal, Other: Daewoong Pharm. K. Petrakova: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Roche, Pfizer. G.V. Bianchi: Financial Interests, Personal, Advisory Role: Roche, Eli Lilly, Novartis, Seagen, AstraZeneca/Daichi Sankyo, MSD. M. Martin Jimenez: Financial Interests, Personal, Speaker’s Bureau, Speaker Honoraria: Lilly, Pfizer; Financial Interests, Personal, Advisory Board, Honoraria for Participation in Advisory Boards: Lilly, Pfizer, AstraZeneca, Novartis, Roche-Genentech, GlaxoSmithKline, PharmaMar, Taiho Oncology; Financial Interests, Personal, Research Grant: Novartis, Roche-Genentech. A. Nusch: Financial Interests, Personal, Advisory Role, Consulting/Advisory role: Novartis, Amgen; Financial Interests, Personal, Funding, Research Funding: Novartis; Other, Personal, Travel/Accommodation/Expenses: Novartis; G.S. Sonke: Financial Interests, Institutional, Other, Institutional Reimbursement for Patient Accrual: Novartis; Financial Interests, Institutional, Other, Institutional Reimbursement for Education and Steering Committee Activities: Novartis; Financial Interests, Institutional, Other, Institutional research support: Merck, AstraZeneca, Roche. J.T. Beck: Financial Interests, Institutional, Research Grant, Institutional funding for doing research: AbbVie, Alliance, Argenx, Ascentage Pharma Group, AstraZeneca, Biodesix, Bio-Thera, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech-Roche, Hutchison, Immunomedics, Gilead, MT Group Merck, Nektar, Pfizer, Polynoma, Seattle Genetics, Serono-EMD, Tesaro, TG Therapeutics, Daiichi Sankyo, Exact Sciences, Boehringer Ingelheim, Laekna, Novocure, Mirati Therapeutics, Tarveda Therapeutics, Sumitomo Dainippon Pharma Oncology (formerly Boston Bio), Elpiscience Biopharma, Takeda, Vaccinex, Vincerx Pharma, Ultimovacs, Mersana. J.P. Zarate, Y. Wang, A. Chakravartty, C. Wang: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. D. Slamon: Non-Financial Interests, Personal, Member of the Board of Directors: Biomarin; Non-Financial Interests, Personal, Other, Travel expenses: Biomarin, Pfizer, Novartis; Financial Interests, Personal, Stocks/Shares: Pfizer, Amgen, Seattle Genetics; Financial Interests, Personal, Other, Research funding: Pfizer, Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Consulting: Novartis, Eli Lilly. All other authors have declared no conflicts of interest.

Background

Brain metastases (BM) are a frequent and devastating complication of HER2-positive breast cancer (BC). T-DXd is an antibody-drug conjugate with high activity in pretreated pts but information regarding activity in active BM is limited. Therefore, the prospective, single-arm, phase II TUXEDO-1 trial investigated T-DXd in HER2-positive BC pts with active BM.

Methods

TUXEDO-1 included adult pts with HER2-positive BC and newly diagnosed untreated BM or BM progressing after local therapy, prior exposure to trastuzumab and pertuzumab, and no indication for immediate local therapy. The primary endpoint was intracranial response rate (RR) centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria. Secondary endpoints consisted of extracranial RR, progression-free survival (PFS), overall survival, safety, and quality-of-life. Based on a Simon’s two-stage design (RR under alternative hypothesis >60%; RR under null hypothesis <26%), a total number of 15 pts were enrolled. The null hypothesis was to be rejected with a type I error rate of 5% and a power of 80% if at least 7 responses were observed.

Results

As of December 29^th, 2021, all 15 pts had received at least one dose of T-DXd (60% progressive BM, 70% prior T-DM1). One patient initially assessed as having parenchymal BM was found to have dural metastasis upon restaging and was excluded from efficacy analyses. In the intention-to-treat population, intracranial RR was 73.3% (11/15) (per protocol population: 78.6% [11/14]). At 11 months median follow-up, PFS was 14 months (95% CI 8.48-19.52); two pts died from disease progression. Main non-haematological toxicities consisted of grade 1/2 fatigue (86.7%), nausea (46.7%), and diarrhoea (26.7%). Dose reductions were required in 9 pts; 4 pts had serious adverse events. Grade 2 interstitial lung disease and a symptomatic drop of left-ventricular ejection fraction were observed in one patient each.

Conclusions

In the TUXEDO-1 study, T-DXd yielded high intracranial response rates. Data suggest that T-DXd achieves significant therapeutic effects in the central nervous system and should thus be further explored in this context.

Clinical trial identification

NCT04752059.

Legal entity responsible for the study

Medical University of Vienna, Department of Medicine 1.

Funding

Daiichi Sankyo.

Disclosure

R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. M. Marhold: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: MEDmedia; Financial Interests, Personal and Institutional, Other: Amgen; Financial Interests, Personal and Institutional, Other: Novartis; Financial Interests, Personal and Institutional, Other: Pierre Fabre; Financial Interests, Personal and Institutional, Other: Daiichi; Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Personal and Institutional, Other: Eisai. Z.A. Bago-Horvath: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal and Institutional, Other: Daiichi. T. Fuereder: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Accord; Financial Interests, Personal, Invited Speaker: Merck Darmstadt; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Darmstadt. C.F. Singer: Financial Interests, Personal, Other, consultancy: Amgen; Financial Interests, Personal, Advisory Board, ADVISORY FUNCTION: NOVARTIS; Financial Interests, Personal, Advisory Board, ADVISORY ROLE: ROCHE; Financial Interests, Personal, Other, STUDY SUPPORT: PFITZER; Financial Interests, Personal, Advisory Board, ADVISORY, SPEAKER HONORARIES, STUDY SUPPORT: ASTRAZENECA; Financial Interests, Personal, Invited Speaker, STUDY COORDINATOR: AMGEN; Non-Financial Interests, Principal Investigator, STUDY: AMGEN; Non-Financial Interests, Principal Investigator, STUDY: ASTRAZENECA; Non-Financial Interests, Project Lead, REGISTER: PFITZER. M. Preusser: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: GLG; Financial Interests, Personal, Invited Speaker: CMC contrast; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Mundipharma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other: BMJ journals; Financial Interests, Personal, Writing Engagements: MedMedia; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MEDahead; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Tocagen; Financial Interests, Personal, Invited Speaker: Adastra; Financial Interests, Personal, Invited Speaker: Gan & Lee Pharmaceuticals. All other authors have declared no conflicts of interest.

Background

Patients (pts) with a/mTNBC have limited treatment options and poor prognosis. Combining checkpoint inhibitors with 1L chemotherapy improves outcomes but only in PD-L1+ve a/mTNBC, emphasizing a critical need. Dato-DXd, a TROP2 antibody-drug conjugate (ADC) with potent topoisomerase (TOPO) I inhibitor payload, elicited a 34% objective response rate (ORR) in heavily pretreated a/mTNBC and 52% ORR in a subset naïve to TOPO I-based ADCs. In BEGONIA, an ongoing 2-part, open-label platform study, D (an anti-PD-L1 antibody) combined with other therapies, including ADCs, is being evaluated in 1L a/mTNBC (NCT03742102). Here, we report preliminary results of Dato-DXd + D.

Methods

Unresectable a/mTNBC pts eligible for 1L treatment, regardless of PD-L1/TROP2 status, received intravenous Dato-DXd 6 mg/kg + D 1120 mg every 3 weeks until progression or unacceptable toxicity. Primary endpoints are safety and tolerability. Secondary endpoints include investigator-assessed ORR (RECIST v1.1) and response duration. Data cutoff was Nov 2021.

Results

29 pts received Dato-DXd + D (24 ongoing), 27 had the opportunity to have 2 postbaseline scans. Median (range) follow-up was 3.9 (2–6) months. Confirmed ORR was 20/27 (74%; 95% CI, 54–89); 2 (7%) pts had complete and 18 (67%) had partial responses, all were in response at data cutoff. No dose-limiting toxicities were observed. 4 pts (14%) underwent 1 Dato-DXd dose reduction due to stomatitis, 4 (14%) had 1 Dato-DXd dose delay, and 4 (14%) had 1 D dose delay. No dose modifications were required due to diarrhea. Table: 166MO

Summary of adverse events (AEs), n (%)

Conclusions

Combination of Dato-DXd + D in 1L a/mTNBC demonstrated robust response rates with a manageable safety profile in this preliminary analysis, warranting further investigation. Additional enrollment and analysis of translational data is ongoing. Funding: AstraZeneca/Daiichi Sankyo.

Clinical trial identification

NCT03742102.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Nicole Seneca, PhD, of Parexel (Hackensack, NJ) and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca/Daiichi Sankyo.

Funding

AstraZeneca/Daiichi Sankyo.

Disclosure

P. Schmid: Financial Interests, Personal and Institutional, Other, Employment, consulting or advisory role and research funding: Genentech; Financial Interests, Personal and Institutional, Other, Employment, Honoraria, consulting or advisory role and research funding: Roche; Financial Interests, Personal and Institutional, Other, Honoraria, consulting or advisory role and research funding: AstraZeneca; Financial Interests, Personal and Institutional, Other, Honoraria, consulting or advisory role and research funding: Novartis; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: Pfizer; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Bayer; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Celgene; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Eisai; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Merck; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Puma Biotechnology; Financial Interests, Institutional, Funding, Research Funding: Astellas Pharma; Financial Interests, Institutional, Funding, Research funding: OncoGenex. K.H. Jung: Financial Interests, Personal, Advisory Role, Consulting or advisory role: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Celgene; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Eisai; Financial Interests, Personal, Advisory Role, Consulting or advisory role: MSD; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Novartis; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Roche; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Takeda. P.J. Wysocki: Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: AstraZeneca; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: Astellas; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: Amgen; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: BMS; Financial Interests, Institutional, Other, Honoraria: Gilead; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: IPSEN; Financial Interests, Personal and Institutional, Other, Honoraria, consulting or advisory role and research funding: Immunicom; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: Janssen; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: MSD; Financial Interests, Personal and Institutional, Other, Honoraria, consulting or advisory role and research funding: Merck; Financial Interests, Personal and Institutional, Other, Honoraria, consulting or advisory role and research funding: Pierre Fabre; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: Pfizer; Financial Interests, Personal and Institutional, Other, Honoraria, consulting or advisory role and research funding: Roche; Financial Interests, Personal and Institutional, Other, Honoraria and consulting or advisory role: Sanofi. J. Jassem: Financial Interests, Personal, Other, Personal fees: AstraZeneca; Financial Interests, Personal, Other, Personal fees: Pfizer; Financial Interests, Personal, Other, Personal fees: Roche; Financial Interests, Personal, Advisory Role, Consulting or Advisory role: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting or Advisory role: Pfizer; Financial Interests, Personal, Advisory Role, Consulting or Advisory role: Exact Sciences; Financial Interests, Personal, Other, Conference registration fee: Boehringer Ingelheim. C.X. Ma: Financial Interests, Personal and Institutional, Funding, Funding: Puma; Financial Interests, Personal and Institutional, Funding, Funding: Pfizer; Financial Interests, Personal, Advisory Role, Consulting Fees: Gilead; Financial Interests, Personal, Advisory Role, Consulting Fees: AstraZeneca; Financial Interests, Personal, Advisory Role, Consulting Fees: Athenex; Financial Interests, Personal, Advisory Role, Consulting Fees: Jacobio; Financial Interests, Personal, Advisory Role, Consulting Fees: Natera; Financial Interests, Personal, Advisory Role, Consulting Fees: Bayer Healthcare; Financial Interests, Personal, Advisory Role, Consulting Fees: Biovica; Financial Interests, Personal, Advisory Role, Consulting Fees: Eisai; Financial Interests, Personal, Advisory Role, Consulting Fees: Eli Lilly; Financial Interests, Personal, Advisory Role, Consulting Fees: Novartis; Financial Interests, Personal, Advisory Role, Consulting Fees: Phillips Electronics; Financial Interests, Personal, Advisory Role, Consulting Fees: Sanofi; Financial Interests, Personal, Advisory Role, Consulting Fees: Seattle Genetics; Financial Interests, Personal, Advisory Role, Consulting Fees: Pfizer. R. Fernandes: Financial Interests, Personal, Advisory Role, Consulting fees: Canadian Agency for Drugs and Technologies in Health (CADTH); Financial Interests, Institutional, Other, Honoraria: Bayer; Financial Interests, Institutional, Other, Honoraria: Pfizer; Financial Interests, Institutional, Other, Honoraria: Ipsen; Financial Interests, Institutional, Other, Honoraria: BMS; Financial Interests, Institutional, Other, Honoraria: Merck; Financial Interests, Institutional, Other, Honoraria: Novartis; Financial Interests, Institutional, Other, Honoraria: Janssen. R. Huisden: Financial Interests, Personal, Full or part-time Employment, Personal fees from AstraZeneca during the conduct of the study and outside the submitted work: AstraZeneca. R. Stewart: Financial Interests, Personal, Full or part-time Employment, Personal fees from AstraZeneca, during the conduct of the study and outside the submitted work: AstraZeneca; Financial Interests, Personal, Other, Personal fees from Pfizer, outside the submitted work: Pfizer. P. Vukovic: Financial Interests, Personal, Full or part-time Employment, Personal fees from AstraZeneca during the conduct of the study and outside the submitted work: AstraZeneca. A. Tablante Nunes: Financial Interests, Personal, Full or part-time Employment, Personal fees from AstraZeneca during the conduct of the study and outside the submitted work: AstraZeneca. Z. Nowecki: Financial Interests, Institutional, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Other, Honoraria: Sanofi Aventis; Financial Interests, Institutional, Other, Honoraria: MSD; Financial Interests, Institutional, Other, Honoraria: Roche.

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 ESR1_mut 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 1^st 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.