Abstract OT1-03-21: PALLAS: PAlbociclib Collaborative Adjuvant Study: A randomized phase 3 trial of palbociclib with adjuvant endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer

Background: Cell cycle inhibition is a target of interest for novel cancer therapeutics. Palbociclib (P) is an orally active inhibitor of CDK4/6 which arrests the cell cycle at the G1-S transition. P has demonstrated efficacy in phase II and III randomized trials for first-line and pre-treated hormone receptor positive/HER2 negative (HR+/HER2-) metastatic breast cancer (MBC), with hazard ratios 0.42-0.49 (Finn et al, Lancet Oncol 2015, Turner et al, NEJM 2015), and is approved in combination with letrozole as first-line therapy for HR+/HER2- MBC. Given confirmed benefits of P and endocrine therapy for MBC, the PALLAS study was designed to determine if the addition of P to adjuvant endocrine therapy (ET) improves outcomes over ET alone in HR+/HER2- early breast cancer. Trial Design: PALLAS is an international open label phase III trial randomizing patients to 2 years of P (125 mg daily, 21 days on 7 days off in a 28-day cycle) combined with at least 5 years of provider choice ET (AI, tamoxifen, +/- LHRH agonist), versus ET alone. The primary objective of the study is to compare invasive disease-free survival (iDFS) for the combination of P and ET versus ET alone. Secondary objectives include comparing iDFS excluding cancer of non-breast origin, DRFS, LRRFS, OS, as well as safety. The principal translational science objective is to determine the predictive or prognostic utility of defined genomic subgroups with respect to iDFS and OS. Additional translation objectives include evaluation of tissue and blood biomarkers predictive of benefit or resistance, cfDNA, pharmacogenomics, adherence, BMI, and patient-reported QOL. Eligible patients (pts) may be pre- or post-menopausal, have stage II-III breast cancer, HR+/HER2- by ASCO CAP guidelines, and have recovered from prior therapies. Pts may have already initiated ET, but randomization must occur within 12 months of diagnosis and 6 months of initiation of ET. An FFPE block must be received at the central sample repository for eligibility. Total planned accrual to the trial is 4600 pts, providing 85% power to detect a 25% risk reduction in iDFS from ET alone using a stratified logrank test with an overall one-sided alpha = 0.025. Pts will be randomized 1:1 stratified by stage, receipt of prior chemotherapy, age, and geographic location. Interim analyses for safety, futility/efficacy and sample size re-estimation are planned. PALLAS will open in 9/2015; current accrual will be updated at time of presentation. Citation Format: Mayer E, DeMichele A, Dubsky P, Barry W, Metzger O, Symmans WF, Burstein H, Miller K, Wolff A, Rastogi P, Loibl S, von Minckwitz G, Goulioti T, Zardavas D, Fesl C, Koehler M, Huang Bartlett C, Chen L, Piccart M, Winer E, Gnant M. PALLAS: PAlbociclib Collaborative Adjuvant Study: A randomized phase 3 trial of palbociclib with adjuvant endocrine therapy versus endocrine therapy alone for HR+/HER2- early breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-21.