3994 - Safety and efficacy of Ribociclib (RIBO) + letrozole (LET) in patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC): Interim results from the Italian cohort of the CompLEEment-1 (C-1) study.

Background

The phase IIIb international study C-1 (NCT02941926) aims to assess the safety and efficacy of RIBO + LET in men and women who have not received prior ET for HR+, HER2– ABC. Overall more than 3000 pts were enrolled. Here we present interim efficacy and safety results from the Italian cohort.

Methods

Pts with HR+, HER2– ABC, ≤1 line of prior chemotherapy, and no prior ET for ABC received RIBO (600 mg/day, 3 wk on/1 wk off) + LET (2.5 mg/day). Men and premenopausal women received concomitant goserelin. The primary endpoint was safety and tolerability. Secondary endpoints included time to progression (TTP), overall response rate (ORR) and clinical benefit rate (CBR).

Results

From April 2017, to December 2017, 554 pts were enrolled in the C-1 trial in Italy. Median age was 58 years (range 20–87); 1,1% (6) of pts were male, 29,1% were premenopausal women and 69.3% post-menopausal. 2,3%(13) of pts presented CNS metastases and 4,5% (25) skin involvement at study entry. At the cut-off date for this Analysis (August 8, 2018) 66,1% of the pts were still on treatment, 29,8% discontinued, mainly for progression (18,4%) or AEs (10,3 %). The most common all-grade any-cause AEs were neutropenia (69,7%), nausea (29,6%), and leukopenia (28,7%). Grade 3 or 4 elevations in ALT and AST levels were reported in 6,4% and 4,3%, respectively. Prolongation of the QTcF interval to more than 480 msec occurred in 3.1% of patients. 30,3% of patients required a dose reduction (24% one dose, 24,9% due to AEs). ORR was 20,4% (95% CI, 17,1%-24%) and CBR was 69,7% (95% CI, 65,7%-73,5%). TTP was not reached.

Conclusions

This interim analysis confirm the predictable and manageable safety profile of RIBO in combination with LET as first-line treatment for HR+, HER2– ABC. The Italian C-1 cohort is the largest hormono-sensitive Italian population ever published with a CDK 4/6 inhibitor, including 6 male patients and 13 patients with CNS metastases that could give valuable information on this patient’s subgroups that still represent an unmet need.

Clinical trial identification

EudraCT: 2016-003467-19, release date 2016-12-08 Protocol n. CLEE011A2404 NCT02941926.

Editorial acknowledgement

Legal entity responsible for the study

Novartis Pharma AG.

Funding

Novartis Pharma AG.

Disclosure

M. De Laurentiis: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: astrazeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen. M. Mazza: Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): istituto gentili; Honoraria (self): Celgene; Honoraria (self): astrazeneca. M. Mansutti: Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Celgene. R. Masetti: Honoraria (self), Advisory / Consultancy: genomic Health; Honoraria (self), Advisory / Consultancy: medtronic. Z. Ballatore: Honoraria (self), writing engagement and public speaking: Ipsen. R. Torrisi: Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD. A. Michelotti: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: astrazeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: teva; Advisory / Consultancy: Pfizer. A. Zambelli: Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: astrazeneca. D. Generali: Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): Pfizer; Honoraria (self): Roche. P. Vici: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. A. Fabi: Honoraria (self), Speaker Bureau / Expert testimony: Roche; Honoraria (self), Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Speaker Bureau / Expert testimony: astrazeneca; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer. P. Marchetti: Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: bms; Honoraria (self), Advisory / Consultancy: astrazeneca; Honoraria (self), Advisory / Consultancy: incyte; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: molteni; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD. S. Spazzapan: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Travel / Accommodation / Expenses: gentili; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), principal investigator of trials: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Speaker Bureau / Expert testimony: Pierre Fabre; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses, principal investigator of trials: Roche; Honoraria (self), Travel / Accommodation / Expenses: tesaro; Honoraria (self), Speaker Bureau / Expert testimony: astrazeneca; Research grant / Funding (institution), principal investigator of trials: abbvie. A. Frassoldati: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Speaker Bureau / Expert testimony, plus writing engagement: astrazeneca; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer. G. Sarobba: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: teva. D. Grasso: Full / Part-time employment: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: astrazeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Honoraria (self), Travel / Accommodation / Expenses: pierrefabre. C. Zamagni: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: astrazeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: teva; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: istituto gentili; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy: eliLilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: tesaro. All other authors have declared no conflicts of interest.