M Martin1, C Zielinski2, M Ruiz-Borrego3, E Carrasco4, N Turner5, E M Ciruelos6, M Muñoz7, B Bermejo8, M Margeli9, A Anton10, Z Kahan11, T Csöszi12, M I Casas4, L Murillo13, S Morales14, E Alba15, E Gal-Yam16, A Guerrero-Zotano17, L Calvo18, J de la Haba-Rodriguez19, M Ramos20, I Alvarez21, A Garcia-Palomo22, C Huang Bartlett23, M Koehler24, R Caballero4, M Corsaro25, X Huang23, J A Garcia-Sáenz26, J I Chacón27, C Swift28, C Thallinger29, M Gil-Gil30. 1. Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón, Medicine Department, Universidad Complutense, Madrid, Spain; Oncology Biomedical Research National Network (CIBERONC-ISCIII), Madrid, Spain; GEICAM Spanish Breast Cancer Group, Madrid, Spain. Electronic address: mmartin@geicam.org. 2. Medical Oncology, Central European Cancer Center, Wiener Privatklinik Hospital, Vienna, Austria; CECOG Central European Cooperative Oncology Group, Vienna, Austria. 3. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla, Spain. 4. GEICAM Spanish Breast Cancer Group, Madrid, Spain. 5. Institute of Cancer Research and Royal Marsden, London, UK. 6. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain; Medical Oncology, HM Hospitales Madrid, Madrid, Spain; SOLTI Group on Breast Cancer Research, Barcelona, Spain. 7. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Clinic de Barcelona, Barcelona, Spain; Translational Genomics and Targeted Therapeutics in Solid Tumors (IDIBAPS), Barcelona, Spain. 8. Oncology Biomedical Research National Network (CIBERONC-ISCIII), Madrid, Spain; GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Clínico Universitario de Valencia, Valencia, Spain; Biomedical Research Institute INCLIVA, Valencia, Spain. 9. GEICAM Spanish Breast Cancer Group, Madrid, Spain; B-ARGO Group, Catalan Institute of Oncology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. 10. Oncology Biomedical Research National Network (CIBERONC-ISCIII), Madrid, Spain; GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain. 11. Department of Oncotherapy, University of Szeged, Szeged, Hungary. 12. Department of Oncology, Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelőintezet, Szolnok, Hungary. 13. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Clínico de Zaragoza Lozano Blesa, Zaragoza, Spain. 14. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Universitario Arnau de Vilanova, Lleida, Spain. 15. Oncology Biomedical Research National Network (CIBERONC-ISCIII), Madrid, Spain; GEICAM Spanish Breast Cancer Group, Madrid, Spain; UGCI Medical Oncology, Hospitales Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. 16. Department of Oncology, Institute of Oncology, Sheba Medical Center, Tel-Hashomer, Israel. 17. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Instituto Valenciano de Oncología, Valencia, Spain. 18. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Complejo Hospitalario A Coruña, Coruña, Spain. 19. Oncology Biomedical Research National Network (CIBERONC-ISCIII), Madrid, Spain; GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Universitario Reina Sofia, Córdoba; Instituto Maimonides de Investigación Biomédica (IMIBIC); Universidad de Córdoba, Córdoba, Spain. 20. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Centro Oncológico de Galicia, A Coruña, Coruña, Spain. 21. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Universitario Donostia-Biodonostia, San Sebastián, Spain. 22. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital de León, León, Spain. 23. Pfizer, USA. 24. Pfizer, USA; Repare Therapeutics, Cambridge, USA. 25. Pfizer, Italy. 26. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Clínico Universitario San Carlos, Madrid, Spain. 27. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Medical Oncology, Hospital Virgen de la Salud, Toledo, Spain. 28. Ralph Lauren Centre for Breast Cancer Research, Royal Marsden, London, UK. 29. CECOG Central European Cooperative Oncology Group, Vienna, Austria; Department of Oncology, Medical University of Vienna, Department of Oncology, Vienna, Austria. 30. GEICAM Spanish Breast Cancer Group, Madrid, Spain; Institut Català d'Oncologia (ICO) & IDIBELL, L'Hospitalet, Barcelona, Spain.
Abstract
BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.
BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.
Authors: Diana Lüftner; Peter A Fasching; Renate Haidinger; Nadia Harbeck; Christian Jackisch; Volkmar Müller; Eva Schumacher-Wulf; Christoph Thomssen; Michael Untch; Rachel Würstlein Journal: Breast Care (Basel) Date: 2022-01-20 Impact factor: 2.860
Authors: Tobias Engler; Peter A Fasching; Diana Lüftner; Andreas D Hartkopf; Volkmar Müller; Hans-Christian Kolberg; Peyman Hadji; Hans Tesch; Lothar Häberle; Johannes Ettl; Markus Wallwiener; Matthias W Beckmann; Alexander Hein; Erik Belleville; Sabrina Uhrig; Pauline Wimberger; Carsten Hielscher; Christian M Kurbacher; Rachel Wuerstlein; Michael Untch; Florin-Andrei Taran; Hans-Martin Enzinger; Petra Krabisch; Manfred Welslau; Michael Maasberg; Dirk Hempel; Michael P Lux; Laura L Michel; Wolfgang Janni; Diethelm Wallwiener; Sara Y Brucker; Tanja N Fehm; Andreas Schneeweiss Journal: Geburtshilfe Frauenheilkd Date: 2022-07-12 Impact factor: 2.754
Authors: Michael Untch; Peter A Fasching; Renate Haidinger; Nadia Harbeck; Christian Jackisch; Diana Lüftner; Volkmar Müller; Eva Schumacher-Wulf; Rachel Würstlein; Christoph Thomssen Journal: Geburtshilfe Frauenheilkd Date: 2022-09-30 Impact factor: 2.754