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Breast cancer, metastatic

3504 - Biomarker analyses from the phase 3 PALOMA-2 trial of palbociclib (P) with letrozole (L) compared with placebo (PLB) plus L in postmenopausal women with ER + /HER2– advanced breast cancer (ABC)


08 Oct 2016


Breast cancer, metastatic


Richard Finn


Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435


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

Author affiliations

  • 1 Medical Oncology, UCLA - School of Medicine, 90095 - Los Angeles/US
  • 2 Oncology, Pfizer, Inc, La Jolla/US
  • 3 Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, 94115 - San Francisco/US
  • 4 Medical Oncology, MD Anderson Cancer Center, 77030 - Houston/US
  • 5 Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 6 Medical Oncology, BC Cancer Agency, V5Z4E6 - Vancouver/CA
  • 7 Department Of Medical Oncology, Institut Curie, 75248 - Paris/FR
  • 8 Medical Oncology, Hospital General Universitario Gregorio Marañon, Madrid/ES
  • 9 Medical Oncology, University of Alberta Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 10 Breast Surgery, Kyoto University-Graduate school of medicine, Kyoto/JP
  • 11 Biostatistics, Pfizer, La Jolla/US
  • 12 Oncology, Pfizer, Inc, 10017 - New York/US


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Abstract 3504


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.

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