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
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract
2674 - Multicenter Phase I Trial of Trastuzumab Emtansine (T-DM1) in Combination with Non-Pegylated Liposomal Doxorubicin (NPLD) in HER2[+] Metastatic Breast Cancer (MBC). THELMA Study
Presenter: Elena López-Miranda
Session: Poster Display session 2
Resources:
Abstract