Palbociclib (P) added to endocrine therapy (ET) improves progression-free survival in hormone receptor positive (HR+)/HER-2 negative (HER2-) metastatic breast cancer. The global PALLAS trial (NCT02513394) was designed to determine if the addition of two years of P to adjuvant ET improves invasive disease-free survival (iDFS) over ET alone in patients (pts) with HR+/HER2- early-stage breast cancer.
In this phase III open-label trial, pts with stage II-III HR+/HER2- breast cancer were randomized to receive either 2 years of P with adjuvant ET, or ET alone. Eligible pts were within 12 months of diagnosis and 6 months of initiating adjuvant ET. The primary objective was to compare invasive disease-free survival (iDFS) between arms; secondary objectives include other recurrence endpoints and safety, as well as quality of life, adherence, and translational science. The study had 85% power to detect a 25% improvement in iDFS (0.75 hazard ratio [HR]). Interim analyses (IA) were predefined in the protocol; IA2 was triggered when 67% of events were observed.
5,760 pts (median age 52 years) were randomized and included in the analysis; 1,013 (17.6%) had stage IIA disease and 4,729 (82.1%) stages IIB/III. 4,754 (82.5%) had received prior chemotherapy. At IA2, after a median follow-up of 23.7 months (351 events), iDFS was similar between the two arms, with 3-year iDFS of 88.2% for P and ET, and 88.5% for ET alone (HR 0.93, 95% confidence interval 0.76-1.15), crossing a pre-specified futility boundary. No benefit from P was observed within clinicopathologic subgroups. Grade 3 or 4 neutropenia was more common with P (61.3% vs 0.4%) but febrile neutropenia was uncommon (1.0%). Other all-grade toxicities occurring more often with P included leukopenia, fatigue, thrombocytopenia, anemia, upper respiratory tract infection, and alopecia. 42.2% of pts discontinued P prior to the planned 2 year duration, primarily due to adverse events.
Within the PALLAS trial, at IA2, two years of adjuvant palbociclib with ET did not improve iDFS compared to ET alone. Ongoing long-term follow-up and additional clinical and translational analyses will explore the effect of P in this patient population.
NCT02513394.
Alliance Foundation Trials, LLC; Austrian Breast and Colorectal Cancer Study Group (ABCSG).
Pfizer, Inc.
E.L. Mayer: Advisory/Consultancy, Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Myriad; Research grant/Funding (institution): Roche/Genentech. M.I. Gnant: Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Lilly; Travel/Accommodation/Expenses: Invectys; Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Puma; Travel/Accommodation/Expenses: NanoString; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Medison; Travel/Accommodation/Expenses: Lifebrain; Spouse/Financial dependant: Sandoz. A. DeMichele: Honoraria (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Menarini; Advisory/Consultancy: Context Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Calithera. M. Martin: Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Puma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Amgen; Advisory/Consultancy: Taiho Oncology; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Daiichi-Sankyo; Honoraria (self), Advisory/Consultancy: Pfizer. A. Prat: Honoraria (self), Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (self): BMS; Honoraria (self), Research grant/Funding (institution): Daiichi-Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Research grant/Funding (institution): Nanostring Technologies; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Sysmex Europa GmbH; Research grant/Funding (institution): Medica Scientia Inno Research; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Astellas Pharma. G. Rubovszky: Honoraria (self), Advisory/Consultancy: Pfizer. G. Pfeiler: Advisory/Consultancy: Amgen; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD. E.P. Winer: Advisory/Consultancy: Carrick; Advisory/Consultancy: Jounce; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Roche/Genentech; Advisory/Consultancy: GSK; Advisory/Consultancy, Officer/Board of Directors: Leap; Advisory/Consultancy: InfiniteMD; Advisory/Consultancy: Gi Theraputics; Advisory/Consultancy: Genomic Health; Advisory/Consultancy: Novartis; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Syros. Z. Nowecki: Honoraria (self): Samsung; Honoraria (self): Roche. S. Loibl: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Celgene; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Seattle Genetics; Honoraria (institution): PriME/Medscape; Honoraria (self): Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Advisory/Consultancy: Lilly; Advisory/Consultancy: Samsung; Advisory/Consultancy: Eirgenix; Advisory/Consultancy: BMS; Advisory/Consultancy: Puma; Honoraria (institution): MSD; Honoraria (institution): Immunomedics; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca. O. Metzger: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Breast Cancer Research Foundation; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Komen for the Cure; Advisory/Consultancy: G1 Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: Group Oncoclinicas. D. Fumagalli: Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche/Genentech; Research grant/Funding (institution): Servier; Research grant/Funding (institution): Tesaro. K. Puyana Theall: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. All other authors have declared no conflicts of interest.