LBA1_PR - First-line ribociclib + letrozole in postmenopausal Asian women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-nega...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Presidential Symposium
Presenter Yoon-Sim Yap
Authors Y. Yap1, L. Tseng2, K.L. Blackwell3, D. Cameron4, S. Foo5, V. Sriuranpong6, C. Huang7, T. Chao8, T. Kim9, S. Chen10, K.H. Jung11, K.S. Lee12, J. Sohn13, J.H. Kim14, M. Hou15, Y. Han16, F. Souami17, S. Dhuria16, M. Miller16, S. Verma18
  • 1Department Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 2Department Of Surgery, Taipei Veterans General Hospital, 11217 - Taipei/TW
  • 3Department Of Medicine, Duke University Medical Center, Durham/US
  • 4Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh/GB
  • 5Medical Oncology, Victorian Breast and Oncology Care, Melbourne/AU
  • 6Medical Oncology, Department Of Medicine, Faculty Of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok/TH
  • 7Department Of Surgery, National Taiwan University Hospital, Taipei/TW
  • 8Graduate Institute Of Clinical Medicine, Taipei Medical University Shuang Ho Hospital, Taipei/TW
  • 9Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 10Division Of General Surgery And Breast Surgery, Chang Gung Memorial Hospital, Taipei/TW
  • 11Department Of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 138-736 - Seoul/KR
  • 12Research Institute And Hospital, National Cancer Center, Goyang-si/KR
  • 13Department Of Surgery, Severance Hospital of Yonsei University, 120-752 - Seoul/KR
  • 14Department Of Internal Medicine, Seoul National University Bundang Hospital, Seongnam/KR
  • 15Department Of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung/TW
  • 16Oncology, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 17Oncology, Novartis Pharma AG, Basel/CH
  • 18Department Of Oncology, Tom Baker Cancer Centre, Calgary/CA

Abstract

Background

23% of breast cancer cases worldwide are diagnosed in Asia. Endocrine therapy resistance eventually occurs in most patients (pts) with HR+ ABC. In MONALEESA-2 (NCT01958021), at the planned interim analysis, the selective cyclin-dependent kinase inhibitor ribociclib (LEE011) + letrozole significantly improved progression-free survival (PFS) vs placebo + letrozole in pts with HR+, HER2– ABC (hazard ratio [HR] 0.556; 95% confidence interval [CI] 0.429–0.720; P=0.00000329). Here we present results from pts treated in Asia.

Methods

Postmenopausal women (N=668) with HR+, HER2– ABC with no prior systemic therapy for ABC were randomized 1:1 to receive ribociclib (600 mg/day; 3-weeks-on/1-week-off) + letrozole (2.5 mg/day; continuous) or placebo + letrozole. The primary endpoint was locally assessed PFS, with a predefined subgroup analysis in pts treated in Asia.

Results

MONALEESA-2 enrolled 68 pts (10%) in Asia (35 vs 33 pts; ribociclib vs placebo arm) and 600 pts (90%) outside Asia (299 vs 301 pts). At data cut-off (January 29, 2016), 9 (26%) vs 21 (64%) pts (ribociclib vs placebo arm) in Asia had discontinued treatment, most commonly due to progressive disease (7 [20%] vs 20 [61%] pts); 1 (3%) pt in the ribociclib arm discontinued due to an adverse event (AE; liver enzyme elevation). Grade 3/4 AEs (≥5% pts) were neutropenia (71% vs 0%; ribociclib vs placebo arm), leukopenia (14% vs 0%), and hypertension (3% vs 6%) in pts treated in Asia; and neutropenia (58% vs 1%), leukopenia (22% vs 1%), hypertension (11% vs 11%), liver enzyme elevations (10% vs 3%), and lymphopenia (8% vs 1%) in pts outside Asia. PFS was significantly prolonged with ribociclib + letrozole in pts treated in Asia (HR 0.298; 95% CI 0.134–0.662) and outside Asia (HR 0.602; 95% CI 0.457–0.792).

Conclusions

First-line ribociclib + letrozole significantly prolonged PFS vs placebo + letrozole with an acceptable safety profile in postmenopausal women with HR+, HER2– ABC treated in Asia.

Clinical trial indentification

NCT01958021