Ribociclib plus letrozole in subgroups of special clinical interest with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Subgroup analysis of the phase IIIb CompLEEment-1 trial.

Paul Cottu,Lakshmi Menon-Singh,Hikmat Abdel-Razeq,Jiwen Wu,Michelino De Laurentiis,Miguel Martín,Paolo Marchetti,Fatima Cardoso,Alistair Ring,Javier Salvador Bofill

doi:10.1016/j.breast.2022.01.016

Abstract

BackgroundThe phase IIIb CompLEEment-1 study evaluated ribociclib plus letrozole in patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC). Outcomes were investigated in the following subgroups: central nervous system (CNS) metastases, prior chemotherapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, and visceral metastases plus prior chemotherapy for advanced disease or ECOG PS 2.Patients and methodsPatients with HR+, HER2– ABC without prior hormonal treatment for advanced disease received oral ribociclib (600 mg once daily, 3 weeks on/1 week off) plus letrozole (2.5 mg once daily, continuous). Primary endpoint was safety/tolerability, assessed via occurrence of adverse events (AEs); key secondary endpoints included time to progression (TTP), overall response rate, and clinical benefit rate.Results51 patients had CNS metastases, 194 received prior chemotherapy for advanced disease, 112 had ECOG PS 2, 146 had visceral metastases plus prior chemotherapy, and 77 had visceral metastases plus ECOG PS 2. Safety results were consistent with those in the overall CompLEEment-1 population; no new safety concerns were identified. The AE profile was manageable with low rates of discontinuations due to AEs. TTP in patients with CNS metastases was consistent with the overall study population and shorter for other patient subgroups. Each patient subgroup achieved meaningful clinical benefit from treatment, consistent with the overall population.ConclusionThese findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials.

Highlights

Endocrine therapy (ET) is the treatment of choice for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) [1]; how ever, resistance remains a barrier to long-term clinical benefit, which has led to the development of therapies that reverse or delay this resistance [2]
Patients with central nervous system (CNS) metastases or with visceral metastases plus Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 tended to have a greater number of meta static sites (31.4% and 29.9%, respectively, had ≥5 sites) compared with the overall study population (11.9% had ≥5 sites)
A patient with multiple severity grades for an adverse events (AEs) was only counted under the maximum grade

Summary

Introduction

Endocrine therapy (ET) is the treatment of choice for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) [1]; how ever, resistance remains a barrier to long-term clinical benefit, which has led to the development of therapies that reverse or delay this resistance [2].Ribociclib is an oral, selective, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved for use in combination with ET for the treatment of patients with HR+, HER2– ABC [3,4]. Endocrine therapy (ET) is the treatment of choice for patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC) [1]; how ever, resistance remains a barrier to long-term clinical benefit, which has led to the development of therapies that reverse or delay this resistance [2]. Certain subgroups of patients with HR+ ABC have poorer prognoses compared with other populations, including patients with central ner vous system (CNS) metastases [8,9], patients who have received mul tiple lines of prior chemotherapy [10], patients with visceral metastases ( liver metastases) [11,12], or patients with poor perfor mance status (PS) [13]. The phase IIIb CompLEEment-1 study evaluated ribociclib plus letrozole in patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC). Conclusion: These findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials

Methods

Results

Conclusion