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ABSTRACT: Background
Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.Methods
The intent-to-treat population included 593 patients with KRAS exon 2 wild-type mCRC. Further testing identified 400 patients with extended RAS wild-type disease; of these, 352 (88%) who received ?3 cycles of therapy and had ?1 post-baseline scan were evaluable for response and constituted the per-protocol population (169 cetuximab and 183 bevacizumab). Patients received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) with either weekly cetuximab or biweekly bevacizumab given on day 1 of each 14-day cycle until response, progression or toxicity occurred. The primary endpoint was the objective response rate (ORR) in the per-protocol population. Secondary endpoints included overall survival (OS) and progression-free survival (PFS). The effect of primary tumour location was evaluated.Results
Median OS in the RAS wild-type population was 31 vs 26 months in the cetuximab and bevacizumab groups, respectively (HR 0.76, P?=?0.012). In the per-protocol population, outcomes favoured cetuximab for ORR (77% vs 65%, P?=?0.014) and median OS (33 vs 26 months, HR 0.75, P?=?0.011), while PFS was comparable between groups. The advantage of cetuximab over bevacizumab occurred only in patients with left-sided primary tumours.Conclusions
FOLFIRI plus cetuximab resulted in a significantly higher ORR and longer OS compared to FOLFIRI plus bevacizumab among patients with left-sided tumours. The superior response associated with cetuximab may particularly benefit patients with symptomatic tumours or borderline-resectable metastases. CLINICALTRIALS.Gov identifier
NCT00433927.
SUBMITTER: Heinemann V
PROVIDER: S-EPMC7851157 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Heinemann Volker V von Weikersthal Ludwig Fischer LF Decker Thomas T Kiani Alexander A Kaiser Florian F Al-Batran Salah-Edin SE Heintges Tobias T Lerchenmüller Christoph C Kahl Christoph C Seipelt Gernot G Kullmann Frank F Moehler Markus M Scheithauer Werner W Held Swantje S Miller-Phillips Lisa L Modest Dominik Paul DP Jung Andreas A Kirchner Thomas T Stintzing Sebastian S
British journal of cancer 20201106 3
<h4>Background</h4>Cetuximab plus FOLFIRI improved overall survival compared with bevacizumab plus FOLFIRI in KRAS wild-type metastatic colorectal cancer (mCRC) in FIRE-3, but no corresponding benefit was found for progression-free survival. This analysis aimed to determine whether cetuximab improves response and survival versus bevacizumab among response-evaluable patients receiving first-line FOLFIRI for RAS wild-type mCRC and the effect of primary tumour side on outcomes.<h4>Methods</h4>The i ...[more]