1569PFinal results of randomized phase II trial of metronomic vs weekly oral vinorelbine (OV) as first-line chemotherapy (CT) in advanced NSCLC patients unfit to platinum-based CT (P-CT): Tempo-Lung

Abstract Background Metronomic chemotherapy (CT) is a therapeutic strategy based on a regular, short interval, fixed-dose schedule developed to improve disease control and reduce toxicity. Metronomic oral vinorelbine (m-OV) showed promising results. The trial randomly compared single agent m-OV vs OV standard schedule as first-line treatment in advanced NSCLC patients (pts) unfit for platinum-based CT (P-CT). Methods CT naive pts with advanced NSCLC unfit for P-CT (Creatinine clearance G2; medical conditions impairing P-CT according to physician’s opinion) were 1:1 randomly allocated to arm A: m-OV 50mg x3/week (wk) or arm B: OV 60 mg/m²/wk cycle 1, then 80 mg/m²/wk. Primary objective: progression-free survival without grade 4 toxicity (G4PFS). Secondary objectives: disease control rate (DCR), PFS, overall survival (OS), safety, quality of life. Stratification factors: stage (IIIB vs IV), age (  70 yrs) and ECOG PS (0-1 vs 2). Results Intention-to-treat (ITT) population included 165 pts: 83 pts (A) / 82 (B). Pt characteristics were well balanced (A vs B): mean age 76.1 vs 75.9 yrs; ECOG PS 0-1: 66% vs 62%; Stage IV: 87% vs 94% pts. Median relative dose intensity was 85% vs 69%. Primary endpoint was reached (A vs B) with median G4PFS [95%CI]: 4.0 [2.6-4.3] vs 2.2 [1.5-2.9] months (mo) (p = 0.0068), HR [95%CI] = 0.63 [0.45-0.88]. Secondary efficacy end-points were as follows (A vs B): DCR 63.9% vs 63.4%; median PFS 4.3 vs 3.9 mo; median OS: 7.1 vs 7.6 mo. Treatment related AEs (r-AEs) A vs B were: all grade 61.4% vs 84%; total hematological AEs: 27.7% vs 55.6%. Most common (≥ 5%) grade 3-4 r-AEs (A vs B) were: febrile neutropenia 3.6% vs 6.2%; neutropenia 11% vs 52%; asthenia 4.8% vs 8.6%. One grade 5 AE occurred in each arm (febrile neutropenia, neutropenic sepsis). Conclusions Positive results of first randomized prospective trial: m-OV significantly improved G4PFS as first-line CT in advanced unfit NSCLC pts, with reduced toxicity. Treatment efficacy was similar in both arms. m-OV is a suitable, safe option for first-line therapy of NSCLC pts unfit to P-CT. Clinical trial identification EudraCT: 2014-003859-61. Legal entity responsible for the study Institut de Recherche Pierre Fabre- Pierre Fabre Medicament. Funding Institut de Recherche Pierre Fabre- Pierre Fabre Medicament. Disclosure A. Morabito: Speaker Bureau / Expert testimony, Speaker Bureau: Pfizer; Speaker Bureau / Expert testimony, Speaker Bureau: BMS; Speaker Bureau / Expert testimony, Speaker Bureau: Boehringer Ingelheim; Speaker Bureau / Expert testimony, Speaker Bureau: MSD; Speaker Bureau / Expert testimony, Speaker Bureau: Roche; Speaker Bureau / Expert testimony, Speaker Bureau: AstraZeneca. F. Grossi: Honoraria (self): Ely Lilly; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pierre Fabre; Honoraria (self): BMS; Honoraria (self): Amgen; Honoraria (self): MSD; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): MSD; Advisory / Consultancy: Ely Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: BMS; Honoraria (self): Celgene. R. Ramlau: Advisory / Consultancy: Roche; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis. T. Ciuleanu: Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Servier; Advisory / Consultancy, Travel / Accommodation / Expenses: A et D Pharma; Travel / Accommodation / Expenses: Ipsen. G.L. Ceresoli: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Astellas; Advisory / Consultancy: Boehringer Ingelheim. J. Bosch Barrera: Honoraria (self): Pierre Fabre; Honoraria (self): Roche; Honoraria (self): BMS; Advisory / Consultancy: Boehringer Ingelheim. P. Landreau: Full / Part-time employment: Pierre Fabre. S. Gautier: Full / Part-time employment: Pierre Fabre. C. Ta Thanh Minh: Full / Part-time employment: Pierre Fabre. A. Camerini: Speaker Bureau / Expert testimony, expert testimony: Pierre Fabre; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.