STEAM—Sequential versus Concurrent FOLFOXIRI/Bevacizumab in Metastatic Colorectal Cancer

5-fluorouracil/leucovorin/oxaliplatin plus bevacizumab (FOLFOX-BEV) is the most commonly used first-line treatment option for metastatic colorectal cancer (mCRC). Moreover, 3-drug concomitant chemotherapy (CT) + bevacizumab (BEV) (cFOLFOXIRI-BEV) significantly improved efficacy versus FOLFIRI-BEV for first-line treatment of mCRC, but the safety and impact of subsequent fluoropyrimidine-BEV maintenance therapy require further definition.1 Bendell and colleagues presented results from the randomized, open-label, phase 2 STEAM trial that assessed efficacy of first-line cFOLFOXIRI-BEV versus FOLFOX-BEV, and the safety of alternating 2-drug CT (FOLFOX and FOLFIRI) + BEV treatment monthly in a sequential (sFOLFOXIRI-BEV) regimen.2 Patients with unresectable, previously untreated mCRC were randomized 1:1:1 to BEV-containing (5-mg/kg) arms (cFOLFOXIRI, sFOLFOXIRI [alternating FOLFOX and FOLFIRI every 4 weeks], or FOLFOX every 3 weeks) in a 4- to 6-month induction phase, followed by BEV-containing maintenance therapy. Stratification factors included extent of metastatic disease and tumor location. Primary objectives of the study included first-line objective response rate (ORR), progression-free survival (PFS), and safety. Secondary objectives included resection and conversion to resectable disease rates, time to second-line PFS, and overall survival.

Among 280 enrolled patients, 186 remained in the study on July 1, 2015. Efficacy and safety data are shown in the Table. The authors concluded that while not statistically significant, there was a trend of increased ORR, PFS, and metastatic resection rates with cFOLFOXIRI-BEV versus sFOLFOX-BEV as first-line therapy of mCRC. All 3 regimens were well-tolerated. These interim results from STEAM support the role of FOLFOXIRI-BEV as a first-line treatment option in selected patients with mCRC. Biomarker assessment, additional subgroup analyses, and outcomes in the second-line treatment phase are in progress.

(n = 93)
(n = 92)
(n = 95)
ORR in first-line, % 60 62 47
Preliminary median PFS in first-line, months (90% confidence interval) 11.7 (9.9-16.6) 10.7 (8.7-12.7) 9.3 (7.7-10.4)
Liver resection required, % 15 10 7
Grade ≥3 treatment-emergent adverse events (TEAEs), % 90 87 82
TEAEs leading to withdrawal, % 41 33 38
Fatal TEAEs, % 3 4 3

  1. Bazarbashi S, et al. Cancer Med. 2015;4:1505-1513.
  2. Bendell JC, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract 492.