Abstract 3994
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.
Resources from the same session
2037 - Updated survival analysis of the randomized phase III trial comparing S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer (SALTO) by the Dutch Colorectal Cancer Group.
Presenter: Johannes Kwakman
Session: Poster Display session 2
Resources:
Abstract
3053 - JFMC51-1702-C7: Phase II study investigating efficacy and safety of trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) in patients (pts) with metastatic colorectal cancer (mCRC) refractory or intolerant to standard chemotherapies.
Presenter: Keisuke Kazama
Session: Poster Display session 2
Resources:
Abstract
3183 - Bevacizumab plus trifluridine/tipiracil in elderly patients with previously untreated metastatic colorectal cancer (KSCC 1602): A single-arm, Phase 2 study
Presenter: Akitaka Makiyama
Session: Poster Display session 2
Resources:
Abstract
3233 - Biweekly TAS-102 and Bevacizumab as a Third-Line Chemotherapy for metastatic colorectal cancer: A Phase II Multicenter Clinical Trial (TAS-CC4 study)
Presenter: Yoichiro Yoshida
Session: Poster Display session 2
Resources:
Abstract
5907 - Liquid biopsy concordance based on clonality and timing of testing in patients with metastatic colorectal cancer
Presenter: Pashtoon Kasi
Session: Poster Display session 2
Resources:
Abstract
1866 - Plasma clearance of RAS mutation under therapeutic pressure is a rare event in metastatic colorectal cancer
Presenter: Emilie Moati
Session: Poster Display session 2
Resources:
Abstract
2312 - High Circulating miR-1247 is a marker for poor prognosis in patients with metastatic colorectal cancer treated with chemotherapy and cetuximab
Presenter: Jakob Schou
Session: Poster Display session 2
Resources:
Abstract
5602 - Clinical relevance of circulating tumor (ct)DNA genotyping for first line cetuximab-based treatment monitoring in metastatic colorectal cancer (mCRC): a prospective multicentric study
Presenter: JOANA Vidal Barrull
Session: Poster Display session 2
Resources:
Abstract
3182 - Clonal hematopoiesis mutations in plasma cfDNA RAS/BRAF genotyping of metastatic colorectal cancer
Presenter: Beili Wang
Session: Poster Display session 2
Resources:
Abstract
5205 - Immune status of patients with different stages of colorectal cancer with and without circulating tumor cells
Presenter: Anastasia Sitkovskaya
Session: Poster Display session 2
Resources:
Abstract