PALOMA3: A double-blind, phase III trial of fulvestrant with or without palbociclib in pre- and post-menopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer that progressed on prior endocrine therapy.

Breast Cancer—HER2/ER
Session Type and Session Title: 
Oral Abstract Session, Breast Cancer—HER2/ER
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr LBA502)
Nicholas C. Turner, Jungsil Ro, Fabrice Andre, Sherene Loi, Sunil Verma, Hiroji Iwata, Nadia Harbeck, Sibylle Loibl, Cynthia Huang Bartlett, Ke Zhang, Carla Giorgetti, Sophia Randolph, Maria Koehler, Massimo Cristofanilli; Royal Marsden, London & Surrey, United Kingdom; Natl Cancer Ctr, Goyang-si, Korea South; Institut Gustave Roussy, Villejuif, France; Peter MacCallum Cancer Centre, East Melbourne, Australia; Sunnybrook Odette Cancer Centre, Toronto, ON, Canada; Aichi Cancer Center Hospital, Nagoya, Japan; University of Munich, Otterfing, Germany; German Breast Group, Neu-Isenburg, Germany; Pfizer Oncology, New York, NY; Pfizer Inc, San Diego, CA; Pfizer, Milan, Italy; Pfizer Oncology, La Jolla, CA; Pfizer Oncology, Narberth, PA; Thomas Jefferson University, Philadelphia, PA

Abstract Disclosures


Background: The growth of hormone receptor (HR) positive breast cancer (BC) is dependent on the cyclin dependent kinases CDK4/6, that promote G1-S phase cell cycle progression. Resistance to endocrine treatment remains a major clinical problem for patients with hormone receptor positive breast cancer. The PALOMA3 study assessed the efficacy of palbociclib and fulvestrant in endocrine-resistant advanced breast cancer. Methods: In this double-blind phase 3 study women with HR positive/HER2 negative advanced metastatic BC whose cancer had relapsed or progressed on prior endocrine therapy, were randomized 2:1 to palbociclib (Palbo, 125 mg/d orally for 3 wk followed by 1 wk off) and fulvestrant (F, 500 mg per standard of care) or placebo (PLB) and F. Pre- and peri-menopausal women also received goserelin. One previous line of chemotherapy for metastatic disease was permitted. The primary endpoint was investigator assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), response assessment, patient-reported outcomes, and safety and tolerability. A pre-planned interim analysis was performed after 195 PFS events by an independent data monitoring committee. Results: 521 pts were randomized, 347 to receive Palbo+F and 174 to PLB+F. Baseline characteristics were well balanced. The median age was 57 and 56 years, 79% were post-menopausal, 60% had visceral disease, and 79% were sensitive to prior endocrine therapy. Prior therapy included chemotherapy for advanced disease in 33% of pts. At the time of the interim analysis the study met the primary endpoint, median PFS was 9.2 months for Palbo+F and 3.8 months for PLB+F (HR 0.422, 95% CI 0.318 to 0.560, P<0.000001). Consistent benefit from Palbo was seen in pre- and post-menopausal women. The most common adverse effects Palbo+F versus PLB+F were neutropenia (78.8% vs. 3.5%), leucopenia (45.5% vs. 4.1%), and fatigue (38.0% vs. 26.7%). Febrile neutropenia was reported in 0.6% pts on Palbo+F and 0.6% pts on PLB+F. The discontinuation rate due to adverse events was 2.0% on Palbo and 1.7% on PLB. Conclusions: Palbociclib combined with fulvestrant improved progression free survival in hormone receptor positive advanced breast cancer that had progressed on prior endocrine therapy, and can be considered as a treatment option for these patients. Clinical trial information: NCT01942135