116O - Palbociclib (PAL) plus letrozole (L) as first-line (1L) therapy (tx) in postmenopausal Asian women with estrogen receptor–positive (ER+)/human epid...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Breast cancer
Topics Anticancer agents
Biomarkers
Breast Cancer, Metastatic
Presenter Seock-Ah Im
Citation Annals of Oncology (2016) 27 (suppl_9): ix35-ix41. 10.1093/annonc/mdw577
Authors S. Im1, H. Mukai2, I.H. Park3, N. Masuda4, C. Shimizu5, S.B. Kim6, Y. Im7, S. Ohtani8, C.H. Bartlett9, D.R. Lu10, A. Mori11, E. Gauthier12, R.S. Finn13, M. Toi14
  • 1Department Of Internal Medicine, Seoul National University Hospital, Cancer Research Institute Seoul National University College of Medicine, 03080 - Seoul/KR
  • 2Department Of Breast And Medical Oncology, National Cancer Center Hospital East, 277-8577 - Chiba/JP
  • 3Center For Breast Cancer, National Cancer Center, 10408 - Goyangsi/KR
  • 4Department Of Surgery, Breast Oncology, NHO Osaka National Hospital, 5400006 - Osaka/JP
  • 5Department Of Breast And Medical Oncology, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 6Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 138-736 - Seoul/KR
  • 7Department Of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 8Department Of Breast Surgery, Hiroshima City Hospital, 730-8518 - Hiroshima/JP
  • 9Clinical Oncology, Pfizer Inc, 10017 - New York/US
  • 10Oncology Clinical Statistics, Pfizer, 92121 - La Jolla/US
  • 11Clinical Oncology, Pfizer S.r.l., 20152 - Milan/IT
  • 12Clinical Oncology, Pfizer, 92121 - La Jolla/US
  • 13Division Of Hematology/oncology, David Geffen School of Medicine, 90404 - Los Angeles/US
  • 14Department Of Breast Surgery, Kyoto University Graduate School of Medicine, 606-8507 - Kyoto/JP

Abstract

Background

Hormone tx (HT) is a mainstay 1L tx for ER+ mBC. PAL is a selective inhibitor of cyclin-dependent kinases (CDK) 4/6. In the PALOMA2 trial, PAL+L as 1L mBC tx prolonged progression-free survival (PFS) v placebo (P)+L in patients (pts) with ER+ mBC. Median PFS (mPFS) (primary analysis) was 24.8 v 14.5 m, respectively (HR 0.58; P

Methods

666 postmenopausal pts not given systemic tx for their ER+/HER2– mBC were randomized 2:1 to PAL (125 mg/d oral [3 wk on, 1 wk off]) + L (2.5 mg daily) or P+L. Primary endpoint was investigator-assessed PFS. Other key endpoints were response rate (RECIST 1.1) and safety. Tumor evaluations were every 12 wk. Safety and blood count assessments were at screening, biweekly during cycles 1–2, and on D1 of later cycles.

Results

95 Asian pts (65 PAL+L; 30 P+L) enrolled. Median age was 60 (range, 43–88) yr. Baseline characteristics: distant relapse (78%), de novo disease (20%), or local/locoregional recurrence (2%); prior (neo)adjuvant HT (66%), measurable disease (83%); ≥2 organs involved (73%); disease sites mostly involved bone (66%), lymph node (54%), and lung (39%); ECOG performance status (PS) 0–1/2 (94%/6%), for PS 2, 6/65 pts were from the PAL+L arm. Investigator-assessed mPFS was 25.7 m (95% CI 19.2–NE) for PAL+L v 13.9 m (7.4–22.0) for P+L (HR 0.48 [0.27–0.87], 1-sided P=.007; independent radiologic assessment: HR 0.44 [0.23–0.84]; 1-sided P=.005). All causality treatment-emergent adverse events (AEs) for all grades (Gr) occurred in 100%/97% of pts (PAL+L/P+L). The most common AEs (all Gr; Gr 3–4) by treatment arms were for the clustered preferred terms of neutropenia (95%/13%; 89%/3%), infections (66%/50%; 5%/0%), and stomatitis (49%/20%; 0%/0%). Due to AEs, 57%/3% of pts had ≥1 dose level reduction of PAL/P and 8%/0% of pts discontinued PAL/P.

Conclusions

In Asian pts with ER+ mBC, PAL+L improved PFS v P+L. Treatment was mostly tolerable; neutropenia was generally manageable with dose modifications. PAL+L should be considered as 1L HT for Asian women with mBC.

Clinical trial indentification

NCT01740427

Legal entity responsible for the study

Pfizer, Inc

Funding

Pfizer, Inc

Disclosure

S-A. Im: Received research funding from AstraZeneca, advisory role for AstraZeneca, Roche, Novartis, and Hanmi. H. Mukai: honoraria from AstraZeneca, Eisai, Novartis Pharma and Taiho Pharmaceutical; research funding from Chugai Pharmaceutical, Nippon Kayaku, Novartis Pharma, Pfizer Japan, and Sanofi. N. Masuda: honoraria from Chugai, AstraZeneca, and Kyowa-Hakko Kirin; research funding from Chugai, Novartis, Pfizer, AstraZeneca, Lilly, MSD, and Kyowa-Kirin. C. Shimizu: research funding from Pfizer, Eli-Lily, Chugai, and the Ministry of Health, Labor and Welfare. C.H. Bartlett: Pfizer employee and a Pfizer stockholder. D.R. Lu, A. Mori, E. Gauthier: Employee of Pfizer and Pfizer stockholder. R.S. Finn: Consultant advisory role with Pfizer, Bayer, Novartis, Bristol Myers-Squibb; research funding from Pfizer. All other authors have declared no conflicts of interest.