LBA15 - Biomarker analyses from the phase 3 PALOMA-2 trial of palbociclib (P) with letrozole (L) compared with placebo (PLB) plus L in postmenopausal women...

Date 08 October 2016
Event ESMO 2016 Congress
Session Breast cancer, metastatic
Topics Biomarkers
Breast Cancer, Metastatic
Presenter Richard Finn
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors R. Finn1, Y. Jiang2, H. Rugo3, S.L. Moulder4, S. Im5, K.A. Gelmon6, V. Dieras7, M. Martin8, A.A. Joy9, M. Toi10, E. Gauthier2, D.R. Lu11, C.H. Bartlett12, D. Slamon1
  • 1Medical Oncology, UCLA - School of Medicine, 90095 - Los Angeles/US
  • 2Oncology, Pfizer, Inc, La Jolla/US
  • 3Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 4Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 5Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 6Medical Oncology, BC Cancer Agency, V5Z4E6 - Vancouver/CA
  • 7Department Of Medical Oncology, Institut Curie, 75248 - Paris/FR
  • 8Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 9Medical Oncology, University of Alberta Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 10Breast Surgery, Kyoto University-Graduate school of medicine, Kyoto/JP
  • 11Biostatistics, Pfizer, La Jolla/US
  • 12Oncology, Pfizer, Inc, 10017 - New York/US



PAL, a cyclin-dependent kinase (CDK) 4 and 6 inhibitor, demonstrated synergy with hormonal blockade in endocrine therapy (tx)–naive and endocrine-resistant ER+ breast cancer models. Sensitive cell lines had elevated levels of retinoblastoma (Rb) and CCND1 (cyclin D1) and decreased levels of CDKN2A (p16) by gene expression. PALOMA-2 demonstrated a significant improvement in median progression-free survival (mPFS) with PAL + L vs P + L (24.8 vs 14.5 mo; hazard ratio [HR], 0.58; P < 0.001) in postmenopausal ER + /HER2– ABC patients (pts) not given prior systemic tx for their advanced disease. Overall survival follow-up for this study remains active. Based on preclinical observations, we performed biomarker analyses to identify potential markers of clinical response.


666 pts were randomized 2:1 to receive PAL + L or P + L. The primary endpoint was investigator-assessed PFS. Tumor tissues from the original diagnostic or metastatic specimen were required from all pts. We performed a central blinded analysis using immunohistochemistry (H-score ≥1 defined positivity) for ER, Rb, p16, cyclin D1, and Ki-67 (proliferative indices based on 15%, 20%, and 40% cutpoints).


568 pts (85%) had tumor tissue available and 566 samples were evaluable for ER. Central review confirmed 89% as ER + ; ER median [interquartile range] H-scores: PAL + L, 120 [45-170]; P + L, 110 [38-158]). By H-scores, PFS improvement with PAL + L was observed in all ER quartiles, Rb+ pts (>90% of intent-to-treat population; 24.2 vs 13.7 mo; HR, 0.53; P < 0.0001), and p16+ pts (85%; 24.8 vs 13.8 mo; HR, 0.52; P < 0.0001). A trend was noted toward a PAL + L benefit for the p16- pts (n = 59); Rb- pts (n = 29) were too few to draw conclusions. In cyclin D1+ pts' tumor samples (97%), the benefit did not vary with H-score. Ki-67 index values did not reveal a pt group with better or worse PFS with PAL + L.


ER+ pts benefit from the addition of a CDK 4/6 inhibitor. Biomarker analyses on cell cycle–related genes did not reveal additional markers with sensitivity to PAL + L beyond ER+.

Clinical trial identification


Legal entity responsible for the study

Pfizer, Inc


Pfizer, Inc


R. Finn: Consultant: Pfizer, Merck, Bayer, Novartis, Bristol Myers Squibb. Y. Jiang: Employee and stock ownership: Pfizer, Inc. H. Rugo: Dr. Rugo does not receive funding personally. Funding is provided to her institution for the conduct of clinical trials sponsored by Pfizer. S.L. Moulder: Genentech; Oncothyreon; Pfizer Research Funding Institution. S-A. Im: AstraZeneca Grant Self AstraZeneca, Novartis, Roche Advisory role Self. V. Dieras: Roche, Pfizer, Novartis Consultant/Advisory Role Self Roche, Pfizer, Novartis Speakers' Bureau Self. M. Martin: Amgen; Novartis Honoraria Self Celgene; Novartis; Pfizer; Roche Pharma AG Consultant/Advisory Role Self Novartis Research Funding Self. A.A. Joy: Pfizer Advisory Board Self. M. Toi: Pfizer Research funding Self (department). E. Gauthier: Employee and stockholder: Pfizer, Inc. D.R. Lu: Pfizer Employee and stockholder. C.H. Bartlett: Pfizer Employee and stockholder Self. D. Slamon: Pfizer Stock Ownership; Travel Accommodations or Expenses Self BioMarin Leadership; Stock Ownership; Travel Accommodations or Expenses Self . All other authors have declared no conflicts of interest.