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
2672 - Changes in clinico-pathological characteristics of vulvar cancer in Japan: increasing oldest-old, stage-shifting, and decreasing cohort-level survival
Presenter: Shin Nishio
Session: Poster Display session 2
Resources:
Abstract
4306 - Tumor Treating Fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase 3 INNOVATE-3/ENGOT-ov50 study
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
5136 - Randomized, phase 1b/2 study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Presenter: Susana Banerjee
Session: Poster Display session 2
Resources:
Abstract
2296 - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION
Presenter: Jung-Yun Lee
Session: Poster Display session 2
Resources:
Abstract
2732 - A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer
Presenter: Ana Oaknin
Session: Poster Display session 2
Resources:
Abstract
4404 - ENGOT-EN9/LEAP-001: a phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer
Presenter: Christian Marth
Session: Poster Display session 2
Resources:
Abstract
4564 - Phase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
4933 - Updated data of Epitopes-HPV02 trial and external validation of efficacy of DCF in prospective Epitopes-HPV01 study in advanced anal squamous cell carcinoma. Pooled analysis of 115 patients
Presenter: Stefano Kim
Session: Poster Display session 2
Resources:
Abstract
2301 - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)
Presenter: Alexandra Gilbert
Session: Poster Display session 2
Resources:
Abstract
5773 - A prospective study of diffusion-weighted magnetic resonance imaging for predicting outcome following chemoradiotherapy, in squamous cell carcinomas of the anus.
Presenter: Rebecca Muirhead
Session: Poster Display session 2
Resources:
Abstract