Background: Addition of ribociclib to aromatase inhibitors significantly increased median progression-free survival in postmenopausal women in the MONALEESA-2 trial and premenopausal women in the MONALEESA-7 trial with hormone receptor–positive (HR+), human epidermal growth factor 2–negative (HER2−) advanced breast cancer (ABC). The global phase 3b CompLEEment-1 trial (Clinicaltrials.gov, NCT02941926) was designed to assess this treatment approach in a cohort of patients with HR+/HER2− ABC that was larger and more diverse than that of the MONALEESA program, particularly in the United States where underrepresented/underserved patient groups were targeted. Here we present the first interim safety analysis of the subset of US patients in the CompLEEment-1 trial.

Methods: Women (premenopausal and postmenopausal) and men with HR+/HER2− ABC, ≤1 line of prior chemotherapy, Eastern Cooperative Oncology Group performance status ≤2, and no prior endocrine therapy for ABC received open-label treatment with ribociclib (600 mg/d, 3 weeks on/1 week off) and letrozole (2.5 mg/d). Men and premenopausal women were required to use concomitant goserelin (3.6-mg subcutaneous implant every 28 days). Targeted enrollment in the overall study is ˜3000 patients. Patients with ≥56 days of follow-up at the data cutoff (October 3, 2017) were included in the first interim analysis (n=1008). The primary endpoint is safety and tolerability.

Results: In the first interim analysis, the US cohort of CompLEEment-1 included 128 patients, 94% of whom were continuing to receive treatment in the study. This cohort included 4 male patients (3%) and 18 patients not identified as white (14%); median age was 62.0 years (Table). The most common adverse events (AEs; >30%) were neutropenia (48%), nausea (45%), and fatigue (36%). The most common grade ≥3 AEs were neutropenia (30%) and leukopenia (6%); all other grade ≥3 AEs occurred in <5% of patients. Rates of AEs leading to discontinuation and dose interruption/adjustment were 5% and 52%, respectively. Four patients experienced at least 1 postbaseline QTcF >480 ms by local assessment. Grade ≥3 increases in alanine aminotransferase and aspartate aminotransferase levels occurred in 3 (2%) and 4 (3%) patients, respectively. There was 1 on-treatment death resulting from a serious AE, bradycardia, that was considered by the investigator to be treatment related.

Conclusions: The first interim safety data for ribociclib + letrozole from US patients in the CompLEEment-1 study, which included a broader population reflective of real-world clinical practice, are consistent with the global study population and previously reported safety profiles from the MONALEESA trials.

Table:

Baseline Characteristics

Demographics Patients, %a 
  (n=128) 
Age, median, y 62.0 
Female 96.9 
Postmenopausal 86.7 
Premenopausal 10.2 
Male 3.1 
Race   
White 82.8 
Black 5.5 
Asian 4.7 
Other 3.1 
Unknown 3.1 
Native American 0.8 
ECOG Performance Status 0/1/2 50.0/45.3/4.7 
Stage at study entry II/III/IV 2.3/3.1/94.5 
Current extent of disease   
Bone only 28.1 
Central nervous system 0.8 
Visceral 53.1 
Liver 20.3 
Lung 38.3 
Other 8.6 
Number of metastatic sites   
≤2 61.7 
3 or 4 24.2 
≥5 14.1 
Demographics Patients, %a 
  (n=128) 
Age, median, y 62.0 
Female 96.9 
Postmenopausal 86.7 
Premenopausal 10.2 
Male 3.1 
Race   
White 82.8 
Black 5.5 
Asian 4.7 
Other 3.1 
Unknown 3.1 
Native American 0.8 
ECOG Performance Status 0/1/2 50.0/45.3/4.7 
Stage at study entry II/III/IV 2.3/3.1/94.5 
Current extent of disease   
Bone only 28.1 
Central nervous system 0.8 
Visceral 53.1 
Liver 20.3 
Lung 38.3 
Other 8.6 
Number of metastatic sites   
≤2 61.7 
3 or 4 24.2 
≥5 14.1 

aUnless otherwise noted.

Citation Format: Lu J, Shtivelband MI, Mitri Z, Chap L, Purkayastha D, Sawhney AG, Beck JT. First-line treatment with ribociclib and letrozole in advanced breast cancer: First interim data from US patients enrolled in the phase 3b CompLEEment-1 clinical trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-25.