First Canadian interim analysis from the phase IIIb CompLEEment-1 ribociclib + letrozole HR+ HER2- advanced breast cancer trial

Abstract

Abstract 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\xa0line 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\xa0=\xa03255pts) 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\xa0=\xa0251) 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 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. 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.