Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3. (November 2018)

• Record Type: Journal Article
• Authors: Cristofanilli, Massimo; DeMichele, Angela; Giorgetti, Carla; Turner, Nicholas C.; Slamon, Dennis J.; Im, Seock-Ah; Masuda, Norikazu; Verma, Shailendra; Loi, Sherene; Colleoni, Marco; Theall, Kathy Puyana; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang
• Is Part Of: European journal of cancer. Volume 104(2018)
• Page Start: 21
• Page End: 31
• Publication Date: 2018-11
• Subjects: Palbociclib -- Fulvestrant -- Advanced breast cancer -- HR+/HER2– -- Long-term response; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.08.011
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. Methods: Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months). Results: By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated <18 months, such as having one disease site (40% vs 29% on palbociclib-fulvestrant and 69% vs 29% on placebo-fulvestrant), bone-only disease (32% vs 22% and 46% vs 17%) and were less heavily pretreated (69% vs 56% and 73% vs 60% had ≤2 prior therapies). Baseline tumour ESR1 and PIK3CA mutation rates were lower among long-term responders in both arms; median oestrogen receptor H-scores were similar, whereas progesterone receptor H-scores were higher among long-term responders. Conclusions: This exploratory analysis demonstrates that some patients with endocrine-resistant MBC derive significant and prolonged benefit when treated with palbociclib-fulvestrant, with fewer patients experiencing similar efficacy with placebo-fulvestrant. The current analysis did not identify specific molecular or clinical factors prognostic of long-term benefit with palbociclib-fulvestrant (ClinicalTrials.gov, NCT01942135 ). Highlights: PALOMA-3 extended follow-up confirms progression-free survival improvement with palbociclib-fulvestrant. With palbociclib-fulvestrant, 29% of patients had a benefit for ≥18 months. Only 15% of patients receiving placebo-fulvestrant had prolonged clinical benefit. Long-term responders in both arms had less disease burden and fewer prior therapies. No prognostic factors of prolonged benefit were identified for the palbociclib arm.