Abstract 1109
Background
CDK4/6 inhibitor Ribociclib (RIBO) was approved by Health Canada in combination with letrozole (LET) for the treatment of HR+, HER2– advanced breast cancer (ABC) in postmenopausal women with no prior therapy for advanced disease. This was based on the significantly prolonged PFS versus placebo + LET observed in the phase 3 MONALEESA-2 trial. (NCT01958021) Here, we report the interim results for the Canadian patients (pts) enrolled in CompLEEment-1 (C-1), an open-label, phase 3b trial evaluating RIBO+LET as first-line therapy in an expanded patient population including pre-menopausal women as well as men.
Methods
Canadian pts with HR+, HER2- ABC, allowed to have received ≤1 line of prior chemotherapy and no prior endocrine therapy (ET) for ABC received RIBO+LET. Treatment regimen and study endpoints have been previously reported (De Laurentiis et al. ASCO 2018. Poster 1056).
Results
Overall, 251 Canadian pts enrolled in C-1 (N = 3255pts) were evaluated in this interim analysis (cut-off date, August 8, 2018). Median duration of exposure was 8.1 months (min; 0.0; max, 22.4). At the time of cut-off 63.3% of patients were still on treatment with the main reason for discontinuation progressive disease. Summary of demographic and baseline characteristics as well as interim efficacy and safety results are shown in Table. Most common grade ≥3 AEs were neutropenia (37.5 %), diarrhoea (2.8%) and fatigue (1.2%). Further details on the clinical impact of adverse events on treatment (i.e. action taken such as dose reductions, interruptions, etc) will be compared to the overall patient population and presented.Table:
337P (N = 251)
Patients treated, n (%) Treated Treatment ongoing Discontinued | N/A 251 (100) 159 (63.3) 92 (36.7) |
Main reasons for d/c PD Treatment related AE Other | N/A 41 (16.3) 23 (9.2) 22 (8.8) |
Median age, y | 58.0 |
Age category <70 y %; ≥ 70 y, n (%) | 200 (79.7); 51 (20.3) |
Postmenopausal, %; Pre/peri-menopausal, n (%) | 189 (75.3):62 (24.7) |
ECOG PS 0/1/2, n (%) | 125 (49.8)/115 (45.8)/11 (4.4) |
Disease History | |
Extent of metastatic disease, n (%) Bone Bone only CNS Visceral Lung Liver Other | N/A 190 (75.7) 53 (21.1) 4 (1.6) 167 (66.5) 118 (47.0) 65 (25.9) 41 (16.3) |
Number of metastatic sites, % 0-2 3-5+ Disease free interval, n (%) De novo Non de novo ≤12 months; >12 months | N/A 131 (52.2) 120 (47.8) N/A 58 (23.1) 192 (76.5) 34 (13.5); 158 (63) |
Best overall response, n (%) | |
CR PR Non-CR/Non-PD SD PD | 1 (0.4) 52 (20.7) 89 (35.5) 63 (25.1) 12 (4.8) |
ORR, n (%); CBR, n (%) | 53 (21.1); 166 (66.1) |
Clinical impact of AEs | |
Dose reduced due to: Neutropenia Alanine aminotransferase increased Aspartate aminotransferase increased | N/A 34 (13.5) 6 (2.4) 2 (0.8) |
Treatment related SAE, % | 12 (4.8) |
Treatment related AE leading to d/c, % | 23 (9.2) |
Conclusions
Canadian pts represent a diverse population. Interim safety and efficacy results are generally consistent with the overall study: response rate - 21.1% for Canada v.s. 20.5% overall; clinical benefit rate - 66.1% Canada v.s 66.1% Overall, safety results were consistent with those observed in RIBO pivotal studies and no new safety signals were observed.
Clinical trial identification
NCT02941926.
Editorial acknowledgement
Legal entity responsible for the study
Novartis.
Funding
Novartis.
Disclosure
C. Ferrario: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Bayer; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck; Honoraria (self): Astellas Pharma; Advisory / Consultancy: Genomic Health; Research grant / Funding (self): Amgen; Research grant / Funding (institution): Casadian therapeutics; Research grant / Funding (institution): Lilly; Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): Janssen Oncology; Research grant / Funding (institution): Zymeworks. A.A. Joy: Advisory / Consultancy: Novartis; Advisory / Consultancy: Roche; Advisory / Consultancy: Teva; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Genomic health; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS. S.F. Dent: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
4616 - Alpelisib (ALP) + Endocrine Therapy (ET) by Last Prior Therapy in Patients (pts) With PIK3CA-Mutated Hormone-Receptor Positive (HR+) Human Epidermal Growth Factor Receptor-2-Negative (HER2–) Advanced Breast Cancer (ABC): Additional Study Cohort in BYLieve
Presenter: Eva Ciruelos
Session: Poster Display session 2
Resources:
Abstract
3592 - PRECYCLE: Impact of CANKADO-based eHealth-support on quality of life in metastatic breast cancer patients treated with palbociclib and endocrine therapy.
Presenter: Tom Degenhardt
Session: Poster Display session 2
Resources:
Abstract
4168 - Efficacy and safety of oral poly (ADP-ribose) polymerase inhibitor fluzoparib in patients with BRCA1/2 mutations and platinum sensitive recurrent ovarian cancer
Presenter: Ning Li
Session: Poster Display session 2
Resources:
Abstract
2785 - Effect of response to last platinum-based chemotherapy in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma in the phase 3 study ARIEL3 of rucaparib maintenance treatment
Presenter: Jonathan Ledermann
Session: Poster Display session 2
Resources:
Abstract
3496 - Integrated safety analysis of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with ovarian cancer in the treatment and maintenance settings
Presenter: Rebecca Kristeleit
Session: Poster Display session 2
Resources:
Abstract
2844 - Clinical factors associated with prolonged response and survival under olaparib as maintenance therapy in BRCA mutated ovarian cancers
Presenter: S.Intidhar Labidi-Galy
Session: Poster Display session 2
Resources:
Abstract
1955 - A Prospective Evaluation of Tolerability of Niraparib Dosing Based on Baseline Body Weight (BW) and Platelet (plt) Count: Blinded Pooled Interim Safety Data from the NORA Study
Presenter: Xiaohua Wu
Session: Poster Display session 2
Resources:
Abstract
2539 - Evaluation of Niraparib 200 mg/d as Maintenance Therapy in Recurrent Ovarian Cancer and Associated Thrombocytopenia in a Real-World US Setting
Presenter: Premal Thaker
Session: Poster Display session 2
Resources:
Abstract
1290 - Niraparib initial dose and its’ management in patients with recurrent high-grade serous ovarian cancer.
Presenter: Jacek Grabowski
Session: Poster Display session 2
Resources:
Abstract
3353 - Results of the 3rd interim analysis of C-Patrol: A non-interventional study on olaparib in German routine clinical practice
Presenter: Jalid Sehouli
Session: Poster Display session 2
Resources:
Abstract