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 Anticancer agents
Colon and Rectal Cancer
Therapy
Biological Therapy
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

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.