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Attend this session at the
2019 ASCO Annual Meeting!

Session: Targeting Breast Cancer: Breaking the Code

Type: Clinical Science Symposium

Time: Saturday June 1, 3:00 PM to 4:30 PM

Location: Hall D1

Genomic markers of early progression on fulvestrant with or without palbociclib for ER+ advanced breast cancer in the PALOMA-3 trial.

Hormone Receptor-Positive

Breast Cancer—Metastatic

2019 ASCO Annual Meeting

Abstract No:

J Clin Oncol 37, 2019 (suppl; abstr 1010)

Author(s): Ben O'Leary, Ros Cutts, Xin Huang, Sarah Hrebien, Yuan Liu, Isaac Garcia-Murillas, Fabrice Andre, Sherene Loi, Sibylle Loibl, Massimo Cristofanilli, Cynthia Huang Bartlett, Nicholas C. Turner; Royal Marsden Hospital, The Institute of Cancer Research, London, United Kingdom; The Institute of Cancer Research, London, United Kingdom; Pfizer Inc., San Diego, CA; Pfizer Inc, San Diego, CA; Institut Gustave Roussy, Villejuif, France; Peter MacCallum Cancer Centre, Melbourne, Australia; German Breast Group (GBG) and Centre for Haematology and Oncology Bethanien, Frankfurt, Neu-Isenburg, Germany; Robert H. Lurie Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago, IL; Pfizer Inc, Collegeville, PA; Royal Marsden NHS Foundation Trust, London, United Kingdom

Abstract Disclosures


Background: Markers of early progression on endocrine therapy in combination with CDK4/6 inhibitors remain limited despite the key role of these combinations in treating of ER+ advanced breast cancer (ABC). We investigated genomic aberrations in patients treated with fulvestrant, with and without palbociclib, with a circulating tumor DNA analysis of baseline plasma in the PALOMA-3 trial. Methods: PALOMA-3 was a phase III trial that randomized 521 patients with ER+/HER2- ABC 2:1 to palbociclib plus fulvestrant (P+F) or placebo plus fulvestrant (F). Using baseline plasma samples, somatic mutations were assessed with a 17 gene panel. Copy number aberrations (CNA) were characterized with a 14 gene panel including ~800 SNPs in 8 commonly altered regions for estimation of tumor purity, the percentage of plasma DNA that was derived from tumor cells. Results for mutations and CNAs were available in 310 pts (203 P+F, 107 F) and were associated with clinical characteristics and progression free survival (PFS) using univariable and multivariable Cox proportional hazards models, including tumor purity and treatment as variables. Results: In the multivariable analysis of the whole cohort, higher baseline tumor purity in plasma was associated with worse PFS (HR 1.20, 95% CI 1.09 – 1.32, p = 0.0001, HR per 10% increase in purity). Baseline TP53 mutation was also associated with shorter PFS (HR 1.84, 95%CI 1.27 – 2.65, p = 0.0011), as was baseline FGFR1 amplification (HR 2.91, 95%CI 1.61 – 5.25, p = 0.0004). PIK3CA and ESR1 mutations had no significant association with PFS in the multivariable model. Palbociclib treatment effect was comparable with the overall trial result (HR 0.43, 95%CI 0.32 - 0.57, p < 0.0001). TP53 mutations were significantly associated with visceral (q = 0.046) and soft tissue/LN metastases (q = 0.042) and the number of disease sites (q = 0.0086) after correction for multiple testing. Conclusions:TP53 mutation, FGFR1 amplification, and tumor purity in plasma identified patients at risk of early progression In PALOMA-3. If validated these results could inform future clinical trials of CDK4/6 inhibitors combinations.

Other Abstracts in this Sub-Category:


1. Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 1004 First Author: Sara M. Tolaney
Category: Breast Cancer—Metastatic - Hormone Receptor-Positive


2. Capivasertib (AZD5363) plus fulvestrant versus placebo plus fulvestrant after relapse or progression on an aromatase inhibitor in metastatic ER-positive breast cancer (FAKTION): A randomized, double-blind, placebo-controlled, phase II trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: 1005 First Author: Robert Hugh Jones
Category: Breast Cancer—Metastatic - Hormone Receptor-Positive


3. A randomized phase II study of palbociclib plus exemestane with GNRH agonist versus capecitabine in premenopausal women with hormone receptor-positive metastatic breast cancer (KCSG-BR 15-10, NCT02592746).

Meeting: 2019 ASCO Annual Meeting Abstract No: 1007 First Author: Yeon Hee Park
Category: Breast Cancer—Metastatic - Hormone Receptor-Positive