229MO Overall survival (OS) of palbociclib (P) plus endocrine therapy (ET) versus capecitabine (CAP) in hormone-receptor+/HER2- metastatic breast cancer (MBC) that progressed on aromatase inhibitors (AIs): Final results of the PEARL study

Background: PEARL study did not show superiority in progression-free survival (PFS) with P+ET versus (vs) CAP in patients (pts) with AI-resistant MBC, but P+ET was better tolerated and showed a significant delay in quality of life deterioration. Final OS data are reported here. Methods: PEARL had two consecutive cohorts: cohort 1 (C1) with 296 pts randomized to P+exemestane vs CAP, and cohort 2 (C2) with 305 pts randomized to P+fulvestrant (F) vs CAP. Secondary endpoints included OS in C2 and in wild-type (wt) ESR1 (measured in ctDNA at baseline) pts (C1+C2). OS analysis was planned when 152 deaths occurred in C2, in order to have an 80% power to detect an increase of 50% in OS from 22 months (m) with CAP to 33 m with P+F or P+ET in wtESR1 pts. Adjusted hazard ratio (aHR) was calculated using a stratified Cox proportional hazard model with treatment arm, stratification factors and number of involved sites as covariates. Results: At data cut-off (11Jan2021), the median follow-up of C2 and wtESR1 pts were 28.0 m and 30.3 m, respectively. Median OS in C2 was 31.1 m with P+F vs 32.8 m with CAP (aHR 1.10, 95% CI, 0.81–1.50; p=0.550). Median OS in wtESR1 pts was 37.2 m with P+ET vs 34.8 m with CAP (aHR 1.06, 95% CI, 0.81-1.37; p=0.683). None of the subgroup analyses showed superiority in OS for P+ET vs CAP. Subsequent therapy was given to 79.8% and 82.9% of pts with P+ET and CAP, respectively. The median number of subsequent lines was 3 (1-10) in the P+ET arm and 3 (1-9) in the CAP arm. First subsequent therapy was CDK4/6 inhibitor+ET in 26.1% of pts in the CAP arm and CAP in 36.1% of pts in the P+ET arm. The median PFS2 defined as time from randomization to the end of first subsequent therapy or death, was similar in both arms either in C2, 18.3 m with P+F vs 17.7 m with CAP (aHR 0.95, 95% CI, 0.73-1.25; p=0.728), and in wtESR1 pts, 18.3 m with P+ET vs 18.2 m with CAP (aHR 1.04, 95% CI, 0.83-1.31; p=0.717). PFS and response did not change in this final analysis. No new safety findings were observed with longer follow-up. Conclusions: Palbociclib + endocrine therapy did not show a statistically superior OS compared to CAP in MBC pts progressing to AIs. Clinical trial identification: NCT02028507. Legal entity responsible for the study: GEICAM Spanish Breast Cancer Group. Funding: Pfizer and AstraZeneca. Disclosure: M. Martin Jimenez: Financial Interests, Personal, Advisory Role: AstraZeneca. Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, and Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. Amgen, Roche/Genentech, Novartis, Daiichi Sankyo, and Pfizer; contracted research fees from Roche, Novartis, and PUMA; Financial Interests, Institutional, Research Grant: Roche. Novartis. PUMA. C. Zielinski: Financial Interests, Personal, Advisory Role: Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier, Shire, Eli Lilly, and Athenex; Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier, Shire, Eli Lilly, and Athenex; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, AstraZeneca, and Merck KGaA. M. Ruiz-Borrego: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, and Lilly; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, and Lilly. E. Carrasco: Financial Interests, Personal, Ownership Interest: Lilly; Financial Interests, Personal, Other, Travel, accommodation support: Roche; Other, Institutional, Research Grant: Roche/Genentech, Bristol Myers Squibb, Novartis, Pfizer, Celgene, AstraZeneca, Merck Sharp & Dohme, Pierre Fabre, and Takeda; Financial Interests, Personal, Advisory Board, Her husband: Bristol Myers Squibb, Novartis, Celgene, Roche Pharma, Janssen, Amgen, Incyte, AbbVie, and Pfizer; Financial Interests, Personal, Research Grant, Her husband's institution: from Celgene, Janssen, Bristol Myers Squibb, Novartis, Celgene, Roche/Genentech, Amgen, Pfizer, and AbbVie. E.M. Ciruelos: Financial Interests, Personal, Advisory Board: Lilly, Novartis, MSD, AstraZeneca, Pfizer and Roche; Financial Interests, Personal, Speaker’s Bureau: Roche, Lilly and Pfizer; Financial Interests, Personal, Other, Travel and congress assistance support: Pfizer and Roche. M. Muñoz: Financial Interests, Personal, Other, Travel and Congress assistance support: Roche, Novartis, Pfizer and Eisai. B. Bermejo: Financial Interests, Personal, Advisory Board: Roche, Novartis and MSD; Financial Interests, Personal, Speaker’s Bureau: Roche, Novartis, MSD, Pfizer and Pierre Fabre; Financial Interests, Personal, Other, Travel and Congress assistance support: Pfizer. M. Margeli: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, and Eisai; Financial Interests, Institutional, Funding: Roche, Pfizer, Novartis, Lilly, AstraZeneca, Eisai, and Kern; Financial Interests, Personal, Other, Travel and Congress assistance support: Roche. A. Anton: Financial Interests, Personal, Advisory Board: Bayer. N. Turner: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Lilly, Merck Sharpe & Dohme, Novartis, Pfizer, Roche/Genentech, Bicycle Therapeutics, Taiho, Zeno pharmaceuticals, Repare therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Merck Sharpe & Dohme, and Guardant Health. E. Alba: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Lilly, Bristol Myers Squibb, Genomic Health, and Nanostring; Financial Interests, Personal, Other, Travel Support: Celgene; Financial Interests, Institutional, Research Grant: Roche, Pfizer, Sysmex, Merck Sharp & Dohme, and Nanostring. J. De La Haba: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Novartis and Lilly. M. Ramos: Financial Interests, Personal, Speaker’s Bureau: Novartis, Roche, and Pfizer. M. Corsaro: Financial Interests, Personal, Stocks/Shares, Employed: Pfizer. Z. Kahan: Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, AstraZeneca and Novartis; Other, Personal, Funding, Travel Support: Pfizer, Roche, AstraZeneca and Novartis; Financial Interests, Personal, Advisory Board: Pfizer, Roche, AstraZeneca and Novartis. M. Gil-Gil: Financial Interests, Personal, Funding: Pfizer, Ferrer International and Esteve Pharma. All other authors have declared no conflicts of interest.