RIBOB: A study on the efficacy and safety of ribociclib in combination with letrozole in older women (≥70 years) with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (aBC) with no prior systemic therapy for advanced disease

Abstract

Abstract Background Ribociclib in combination with endocrine therapy (ET) is the current standard of care in first-line for HR+/HER2- aBC. An increasing proportion of patients who are candidates for ribociclib are older (≥70 years of age). The number of older patients who have participated thus far in ribocicib trials is, however, small, and little data is available on the tolerability of ribociclib in this population, particularly among frail older patients. Previous trials, moreover, do not usually include older patient-specific methods of evaluation (comprehensive geriatric assessment). RIBOB addresses the issue of efficacy and tolerability of ribociclib in older patients, including frail patients and patients with multiple comorbidities as is frequent in clinical practice. Trial design Ribob is a prospective, open lable, single arm trial which will evaluate the clinical efficacy, overall safety and tolerability of ribociclib in combination with letrozole in older women (≥70 years) with HR+/HER2- aBC and no prior hormonal treatment for advanced disease (as per approved indication). Frail patients, patients with comorbidities and patients with altered laboratory tests for whom treatment is deemed adequate and safe by the local investigator are eligible. Exclusion criteria include patients with uncontrolled brain lesions and QTc interval prolongation. A total of 150 patients will be enrolled for treatment with Letrozole (2.5\xa0mg once daily) + ribociclib 600\xa0mg (day 1 to 21 in a 28\xa0day cycle) until progression, intolerable toxicity or patient/physician decision to withdraw. Study end-points include PFS, OS, safety and functionality, which will be evaluated through EORTC QLQ-C30 (modified) and EORTC IL15 questionnaires as well comprehensive geriatric assessment at baseline, 3 months and 1 year. Translational research will include the collection of plasma samples which will be obtained to evaluate aging biomarkers and thymidine kinase and their impact on efficacy and toxicity. Recruitment is open since January/2019. Legal entity responsible for the study UZ Leuven. Funding Novartis. Disclosure N.F. Ponde: Research grant / Funding (self), Travel Grant: Novartis. L. Decoster: Research grant / Funding (self): Boehringer-Ingelheim; Research grant / Funding (self): Roche; Research grant / Funding (self): BMS. E. de Azambuja: Speaker Bureau / Expert testimony, Research grant / Funding (self): Roche; Research grant / Funding (self): GSK. G. Jerusalem: Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): Amgen; Honoraria (self), Research grant / Funding (self): BMS; Honoraria (self): Pfizer; Honoraria (self): Puma; Honoraria (self): Daiichi-Sankyo; Honoraria (self): AZ; Honoraria (self): Lilly; Honoraria (self): Celgene; Research grant / Funding (self): MSD. P. Vuylsteke: Research grant / Funding (self): Roche. H. Wildiers: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy: Celldex; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): PUMA. All other authors have declared no conflicts of interest.