Authors: Antonio Llombart-Cussac, José Manuel Pérez-García, Meritxell Bellet, Florence Dalenc, Miguel J. Gil Gil, Manuel Ruiz Borrego, Joaquín Gavilá, Miguel Sampayo-Cordero, Elena Aguirre, Peter Schmid, Frederik Marmé, Serena Di Cosimo, Joseph Gligorov, Andreas Schneeweiss, Joan Albanell, Pilar Zamora, Duncan Wheatley, Eduardo Martínez-De Dueñas, Kepa Amillano, Javier Cortes; Hospital Arnau de Vilanova, Universidad Catolica, Medica Scientia Innovation Research (MedSIR), Valencia, Spain; IOB, Institute of Oncology, QuironSalud Group, Madrid and Barcelona, Medica Scientia Innovation Research (MedSIR) Barcelona, Spain and Ridgewood, New Jersey, Barcelona, Spain; Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Department of Medical Oncology, Institut Claudius Regaud, IUCT-Oncopole, CRCT, Inserm, Toulouse, France; Breast Cancer Unit & Medical Oncology Department, Institut Català d’Oncologia, IDIBELL, Barcelona, Spain; Hospital Universitario Virgen del Rocío, Seville, Spain; Medical Oncology Department, Fundación Instituto Valenciano de Oncología, Valencia, Spain; Medica Scientia Innovation Research (MedSIR), Barcelona and Ridgewood, Barcelona, Spain; Barts ECMC, Barts Cancer Institute, Queen Mary University of London, and Barts Hospital NHS Trust, London, United Kingdom; Leitung Sektion Translationale Gynäkologische Onkologie Nationales Centrum für Tumorerkrankungen und Universitätsfrauenklinik Heidelberg, Heidelberg, Germany; Biomarker Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Institut Universitaire de Cancérologie AP-HP, Sorbonne Université, Medical Oncology Department Tenon Hospital, Paris, France; University Hospital Heidelberg, Heidelberg, Germany; Medical Oncology, Hospital del Mar, Barcelona, Spain; Hospital Universitario La Paz, Medical Oncology Department, Madrid, Spain; Royal Cornwall Hospitals NHS Trust, Truro, United Kingdom; Hospital Provincial Castellón, Servicio de Oncología, Castelló De La Plana, Spain; Hospital Universitari Sant Joan de Reus, Reus, Spain; IOB Institute of Oncology, Quironsalud Group, Madrid and Barcelona, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Medica Scientia Innovation Research (MedSIR), Barcelona and Ridgewood, Barcelona, Spain
Research Funding: Pfizer
Background: The CDK4/6 inhibitor palbociclib (P) in combination with letrozole (L) has become a standard first-line treatment for patients (pts) with luminal metastatic breast cancer (MBC) (PALOMA-1 & 2 trials). Meanwhile, the anti-estrogen fulvestrant (F) showed to be superior to anastrozole in the same population (FALCON trial). We aimed to identify the best endocrine agent to combine with P in this first-line scenario.
Methods: A total of 486 pts with ER[+]/HER2[-] MBC with no prior therapy in the advanced setting and endocrine sensitive criteria (relapse > 12 months [mo] after the end of adjuvant endocrine therapy or diagnosed with “de novo” metastatic disease) were randomly assigned (1:1 ratio) to receive P (oral 125 mg/day [d]; 3 wks on/1 wk off) plus F 500 mg/d (I.M Days 0, 14, 28, and then every 28 d) or PL (oral 2.5 mg/d). Pts were stratified by visceral involvement and type of disease presentation (“de novo”/recurrent). Primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and safety. 254 events were needed with 80% power to detect a hazard ratio (HR) ≤0.7 in favor of PF (2-sided α = 0.05).
Results: By March 9th, 2020, 256 PFS events occurred. Pts characteristics were well balanced. Median age was 62 years (range: 25–90), 56.6% were ECOG 0, 40.7% had “de novo” metastatic disease, 48% had visceral disease, and 43.6% with ≥3 organ sites involved. At median follow-up of 32 mo, median PFS was 27.9 mo (95% confidence interval [CI], 24.2-33.1) with PF and 32.8 mo (95% CI, 25.8-35.9) with PL (HR: 1.1; 95% CI, 0.9-1.5; P = 0.321). No differences were observed for pts with or without visceral involvement (HR: 1.3 and HR: 0.97 respectively, interaction P = 0.275), and for “de novo” or recurrent metastatic disease (HR: 1.1 and HR: 1.1 respectively, P = 0.979). The 4-year OS rate was 67.6% in PF and 67.5% in PL arm (HR: 1; 95% CI, 0.7-1.5; P = 0.986). No differences were observed in ORR or CBR between arms. Grade ≥3 adverse events were similar in both arms, being neutropenia and leukopenia the most frequent. No treatment-related deaths were reported.
Conclusions: This study was not able to identify an improvement in PFS for PF over PL in patients with endocrine-sensitive ER[+]/HER2[-] MBC. As both arms demonstrated comparable 4 years-OS, PF is a reasonable alternative to PL in this setting. Clinical trial information: NCT02491983.