521P - Interim Safety Results from Steam: a Randomized Phase 2 Trial of Sequential and Concurrent Folfoxiri–Bevacizumab (Bev) Vs Folfox–Bev for the First-Line (1L) Treatment (Tx) of Patients (Pts) with Metastatic Colorectal Cancer (Mcrc)

Abstract

ABSTRACT Aim: Recent randomized trials of FOLFOXIRI–BEV in mCRC showed improved progression-free survival (PFS) and overall response rates (ORR) vs either FOLFIRI–BEV or FOLFOX–BEV. The efficacy and safety of FOLFOXIRI–BEV have yet to be investigated in the US. Methods: STEAM (NCT01765582) is a randomized, open-label, US-based, phase 2 trial. Pts are randomized 1:1:1 to FOLFOXIRI–BEV (arm A), sequential FOLFOXIRI–BEV (FOLFOX or FOLFIRI every 2 weeks [q2w] alternating every 2 cycles; arm B), and FOLFOX–BEV (arm C) q2w in previously untreated mCRC (BEV 5 mg/kg in each arm). After a 4- to 6-mo induction phase, pts receive 5-fluorouracil (5-FU)/leucovorin + BEV (5 mg/kg) q2w or capecitabine + BEV (7.5 mg/kg) q3w as maintenance tx until disease progression (PD). Pts receive second-line (2L) 5-FU–based chemotherapy (physician's choice) + BEV (2.5 mg/kg/qw) until 2L PD. Primary objectives are to evaluate 1L ORR (arm A vs arm C), 1L PFS (arms A + B vs arm C), and safety. Adverse events (AEs) were analyzed per a preplanned interim analysis. Results: At data cutoff (12/3/13), 94/280 pts were randomized, and 93 pts had received ≥1 dose of study tx. Pt characteristics were similar across tx arms. The overall AE profile was generally balanced across tx arms; more grade (gr) ≥3 AEs occurred in arm A than in arms B or C (Table). Five (15%) gr 4 neutropenia AEs occurred in arm A; all pts recovered within a week after temporary dose reduction and/or receiving growth factors, and they continued study tx per protocol. One pt in arm A died from unknown reasons; 2 pts died in arm B from PD. Conclusions: The overall AE profile of FOLFOXIRI–BEV in the STEAM trial is similar to previous trials of FOLFOXIRI–BEV. Rates of tx-emergent AEs in the sequential FOLFOXIRI–BEV arm appear similar to the FOLFOX–BEV arm. The trial is continuing with no changes in dosing or design. Adverse Event Category, n (%) Arm A (FOLFOXIRI–BEV) n = 33 Arm B (Sequential FOLFOXIRI–BEV) n = 30 Arm C (FOLFOX–BEV) n = 30 Any TEAE 32 (97) 30 (100) 29 (97) Any gr ≥3 TEAE 26 (79) 15 (50.0) 16 (53) Any gr 4 TEAE Neutropenia Diarrhea CO2 embolism during surgical procedure 6 (18) 5 (15) 1 (3) – ––– – 1 (3)–– 1 (3) Deaths 1 (3) 2 (7) – Any serious TEAE 10 (30) 6 (20.0) 8 (27) Any TEAE of special interest to BEV Bleeding/hemorrhage Hypertension Venous thromboembolic events Proteinuria Wound-healing complications Arterial thromboembolic events Gastrointestinal perforation Congestive heart failure Fistula/abscess Posterior reversible encephalopathy syndrome 15 (45) 8 (24) 6 (18) 1 (3) 2 (6) 2 (6)–1 (3)–– – 15 (50) 10 (33) 6 (20) 4 (13)–––––– – 12 (40) 6 (20) 3 (10) 3 (10) 3 (10) 2 (7) 1 (3)–––– Any gr ≥3 AESI to BEV 6 (18) 4 (13) 6 (20) Any TEAE to dose reduction, tx interruption, or tx discontinuation 26 (79) 12 (40) 18 (60) Any TEAE leading to withdrawal from study tx 8 (24) 1 (3) 4 (13) Any TEAE leading to premature study discontinuation 2 (6) – 1 (3) BEV, bevacizumab; CO2, carbon dioxide; gr, grade; TEAE, treatment-emergent adverse event; tx, treatment Disclosure: H. Hurwitz: Research support and compensated consultant: Genentech, Inc., F. Hoffmann-La Roche, Ltd., Pfizer, Sanofi, Regeneron, Bristo-Meyers Squibb, Eli Lilly, Merck KGA, Novartis, Incite, Threshold Also compensated consultant for GSK; B. Tan: Corporate-sponsored research: Genentech; H. Lenz: Advisory board: Genentech and Roche ad boards Corporate-sponsored research: Clinical trial support, Support through SWOG: Genentech; H. Hochster: Advisory board: Genentech; R. Laeufle: Stock ownership: Roche Other substantive relationships: Genentech employee; N. Sommer: Stock ownership: Roche Other substantive relationships: Genentech employee; J. Young: Stock ownership: Genentech, standard S-SARs Other substantive relationships: Employee, Genentech; M. Byrtek: Stock ownership: Roche Other substantive relationship: Employment at Genentech, a member of the Roche Group; All other authors have declared no conflicts of interest.