521P - Interim safety results from STEAM: A randomized phase 2 trial of sequential and concurrent FOLFOXIRI-bevacizumab (BEV) vs FOLFOX-BEV for the first-...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Herbert Hurwitz
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors H. Hurwitz1, B. Tan2, J. Reeves3, H. Xiong4, H. Lenz5, H. Hochster6, R. Laeufle7, N. Sommer7, J. Young8, M. Byrtek7, J. Bendell9
  • 1Division Of Hematology And Oncology, Duke University Medical Center, 27710 - Durham/US
  • 2Department Of Medicine, Washington University School of Medicine, Saint Louis/US
  • 3N/a, Florida Cancer Specialists–South Region, Fort Myers/US
  • 4N/a, The Center for Cancer and Blood Disorders, Fort Worth/US
  • 5Department Of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles/US
  • 6Medical Oncology, Yale Cancer Center, New Haven/US
  • 7Medical Affairs, Genentech, Inc., South San Francisco/US
  • 8Medical Affairs: Evidence Generation, Genentech, Inc., South San Francisco/US
  • 9Drug Development Unit, Sarah Cannon Research Institute, 37203 - Nashville/US



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.


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.


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.


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


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.