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

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.