Massimo Cristofanilli1, Angela DeMichele2, Carla Giorgetti3, Nicholas C Turner4, Dennis J Slamon5, Seock-Ah Im6, Norikazu Masuda7, Shailendra Verma8, Sherene Loi9, Marco Colleoni10, Kathy Puyana Theall11, Xin Huang12, Yuan Liu13, Cynthia Huang Bartlett14. 1. Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, 710 N Fairbanks Ct, Ste 8-250A, Chicago, IL 60611, USA. Electronic address: Massimo.cristofanilli@nm.org. 2. University of Pennsylvania Abramson Cancer Center, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USA. Electronic address: Angela.DeMichele@uphs.upenn.edu. 3. Pfizer Italia, Via Anna Maria Mozzoni, 12, 20152 Milano, MI, Italy. Electronic address: carla.giorgetti@pfizer.com. 4. Royal Marsden Hospital and Institute of Cancer Research, Fulham Road, London SW3 6JJ, UK. Electronic address: nick.turner@icr.ac.uk. 5. David Geffen School of Medicine, 2020 Santa Monica Blvd, Ste 600, Santa Monica, CA 90404, USA. Electronic address: dslamon@mednet.ucla.edu. 6. Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongro-gu, Seoul 03080, Republic of Korea. Electronic address: moisa@snu.ac.kr. 7. Breast Oncology, NHO Osaka National Hospital, 2 Chome-1-14 Hoenzaka, Chuo, Osaka, Osaka Prefecture 540-0006, Japan. Electronic address: nmasuda@alpha.ocn.ne.jp. 8. Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa, ON, Canada. Electronic address: sverma@toh.ca. 9. Peter MacCallum Cancer Centre, 305 Grattan St., Melbourne, Victoria 3000, Australia. Electronic address: sherene.loi@petermac.org. 10. European Institute of Oncology, Via Ripamonti, 435, 20141, Milan, Italy. Electronic address: marco.colleoni@ieo.it. 11. Pfizer Inc, 300 Technology Square, Cambridge, MA 02139, USA. Electronic address: Kathy.Theall@pfizer.com. 12. Pfizer Oncology, 10555 Science Center Drive, San Diego, CA 92121, USA. Electronic address: xin.huang@pfizer.com. 13. Pfizer Oncology, 10555 Science Center Drive, San Diego, CA 92121, USA. Electronic address: Yuan.Liu@pfizer.com. 14. Pfizer Oncology, 500 Arcola Rd, Collegeville, PA 19426, USA. Electronic address: cynthia.huang@pfizer.com.
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 PIK3CAmutation 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).
RCT Entities:
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).
Authors: Richard S Finn; Hope S Rugo; Karen A Gelmon; Massimo Cristofanilli; Marco Colleoni; Sherene Loi; Patrick Schnell; Dongrui R Lu; Kathy Puyana Theall; Ave Mori; Eric Gauthier; Eustratios Bananis; Nicholas C Turner; Véronique Diéras Journal: Oncologist Date: 2021-03-10
Authors: Lorenzo Gerratana; Jean-Yves Pierga; James M Reuben; Andrew A Davis; Firas H Wehbe; Luc Dirix; Tanja Fehm; Franco Nolé; Rafael Gisbert-Criado; Dimitrios Mavroudis; Salvatore Grisanti; Jose A Garcia-Saenz; Justin Stebbing; Carlos Caldas; Paola Gazzaniga; Luis Manso; Rita Zamarchi; Marta Bonotto; Angela Fernandez de Lascoiti; Leticia De Mattos-Arruda; Michail Ignatiadis; Maria-Teresa Sandri; Daniele Generali; Carmine De Angelis; Sarah-Jane Dawson; Wolfgang Janni; Vicente Carañana; Sabine Riethdorf; Erich-Franz Solomayer; Fabio Puglisi; Mario Giuliano; Klaus Pantel; François-Clément Bidard; Massimo Cristofanilli Journal: Oncologist Date: 2022-07-05 Impact factor: 5.837
Authors: Courtney T van Geelen; Peter Savas; Zhi Ling Teo; Stephen J Luen; Chen-Fang Weng; Yi-An Ko; Keilly S Kuykhoven; Franco Caramia; Roberto Salgado; Prudence A Francis; Sarah-Jane Dawson; Stephen B Fox; Andrew Fellowes; Sherene Loi Journal: Breast Cancer Res Date: 2020-08-18 Impact factor: 8.408