Abstract 1495P
Background
Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven 2nd-line option for advanced gastroesophageal adenocarcinoma (GEA). More patients (pts) are pretreated with docetaxel in the perioperative or 1st-line setting. These pts may benefit from a non-cross resistant chemotherapy backbone regimen.
Methods
This is a multicenter, randomized, investigator initiated, phase II trial. Pts with GEA who have progressed after treatment with a fluoropyrimidine/platinum-containing regimen were randomized 2:1 to either FOLFIRI plus Ram q2w (Arm A) or paclitaxel (d 1, 8, 15 q28d) plus Ram q2w (Arm B). Major endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and safety. Efficacy was assessed in the intention-to-treat (ITT) population and safety in all patients who received at least one dose of treatment.
Results
111 pts (median age 61 years, 65% of pts had prior docetaxel therapy) were enrolled and 110 analyzed within ITT (Arm A, 72; Arm B, 38). There was no significant difference in median OS (A, 6.8 vs. B, 7.6 mos) and median PFS (A, 3.9 vs. B, 3.7 mos). For pts with prior docetaxel (72/110), median PFS was A, 4.6 vs. B, 2.1 mos, HR 0.49, p=0.007 and median OS was A, 7.5 vs. B, 6.6 mos. In the ITT, ORR and DCR was 22% and 61% in Arm A and 11% and 53% in Arm B. In docetaxel pre-treated pts, ORR was 25% in Arm A and 8% in Arm B. DCR was 65% and 37% for Arm A and B respectively. Combination of Ram and FOLFIRI was not associated with more grade 3-5 adverse events in Arm A vs. B (75% vs. 68% of safety population N=106). In the overall population, the most common >= grade 3 adverse events in arm A included neutropenia (12 [17%], leukopenia (10 [14%]), diarrhea (7 [9%]) and stomatitis (7 [10%]; in arm B, they were neutropenia (4 [9%], hypertension (3 [9%]). 57% of the pts in Arm A and 53% in arm B had at least one serious adverse event.
Conclusions
The RAMIRIS trial demonstrated feasibility of the combination of FOLFIRI and Ram. Docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram, providing a rationale for a phase III trial, which is currently ongoing.
Clinical trial identification
NCT03081143; EudraCT-Nr. 2015-005171-24.
Editorial acknowledgement
Legal entity responsible for the study
Institut für Klinische Krebsforschung IKF GmbH.
Funding
Lilly Deutschland GmbH.
Disclosure
P.C. Thuss-Patience: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Merck-Serono; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Servier. S-E. Al-Batran: Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Lilly; Advisory/Consultancy: Bristol-Myers Squibb ; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Bioscience; Advisory/Consultancy: Merck Sharp & Dohme ; Speaker Bureau/Expert testimony: AIO gGmbH ; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung ; Speaker Bureau/Expert testimony: MCI group ; Research grant/Funding (self): Medac; Research grant/Funding (self): Hospira; Research grant/Funding (self): Sanofi; Research grant/Funding (self): German Cancer Aid ; Research grant/Funding (self): German Research Foundation ; Research grant/Funding (self): Federal Ministry of Education and Research ; Research grant/Funding (self): Vifor. E. Goekkurt: Advisory/Consultancy: MSD; Advisory/Consultancy: Servier; Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi. T.J. Ettrich: Advisory/Consultancy: Merck Serono ; Advisory/Consultancy: Sanofi; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Eisai; Advisory/Consultancy: MSD; Travel/Accommodation/Expenses: Ipsen; Research grant/Funding (self): Baxalta/Shire . F. Lordick: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Amgen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Astra Zeneca; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Biontech; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Eli Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Elsevier; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Imedex; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Infomedica; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Iomedico; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Medscape; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MedUpdate; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Serono; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Oncovis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Promedicis; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Springer Nature; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: StreamedUp!; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Zymeworks; Leadership role: Secretary of the German Cancer Society; Leadership role: Chairman of the EORTC Gastrointestinal Tract Cancer Group; Leadership role: President of the International Gastric Cancer Association; Leadership role: Education Director of the European Society for Medical Oncology. M. Stahl: Honoraria (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self): Celgene; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Travel/Accommodation/Expenses: Merck-Serono; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Honoraria (self): Servier; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: Shire. P. Reichardt: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Clinigen Group ; Honoraria (self), Advisory/Consultancy: Lilly; Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Bayer; Advisory/Consultancy: Deciphera ; Honoraria (self): Amgen. D. Pink: Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Clinigen Group; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): PharmaMar. T.O. Götze: Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: MSD Oncology ; Advisory/Consultancy: Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: Roche; Research grant/Funding (self): Deutsche Forschungsgemeinschaft ; Research grant/Funding (self): Gemeinsamer Bundesausschuss . All other authors have declared no conflicts of interest.