FOLFIRI plus cetuximab in patients with liver-limited or non–liver-limited RAS wild-type metastatic colorectal cancer: a retrospective subgroup analysis of the CRYSTAL study

Abstract Background Adding cetuximab to first-line FOLFIRI in the phase 3 CRYSTAL trial significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with KRAS wild-type (wt) or RAS wt metastatic colorectal cancer (mCRC). In this retrosp...

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Published in:European journal of surgical oncology 2016-10, Vol.42 (10), p.1540-1547
Main Authors: Köhne, C.-H, Poston, G, Folprecht, G, Ciardiello, F, Ronga, P, Beier, F, Van Cutsem, E
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Camptothecin - administration & dosage
Camptothecin - analogs & derivatives
Cetuximab
Cetuximab - administration & dosage
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
CRYSTAL
Female
Fluorouracil - administration & dosage
Genes, ras
Hematology, Oncology and Palliative Medicine
Humans
Leucovorin - administration & dosage
LLD
Male
mCRC
Middle Aged
Neoplasm Metastasis
Proto-Oncogene Proteins p21(ras) - genetics
R0 resection
RAS
Retrospective Studies
Surgery
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Summary:Abstract Background Adding cetuximab to first-line FOLFIRI in the phase 3 CRYSTAL trial significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) in patients with KRAS wild-type (wt) or RAS wt metastatic colorectal cancer (mCRC). In this retrospective subgroup analysis of CRYSTAL, we investigated benefit of treatment in patients with KRAS wt or RAS wt tumors according to whether patients had liver-limited disease (LLD) or non-LLD, including assessing the role of cetuximab in downsizing metastases and conversion rates from initially unresectable to resectable disease. Methods PFS, OS, ORR, and R0 resection rates were analyzed according to treatment arm for the LLD and non-LLD subgroups. Results Of the 367 patients with RAS wt tumors, 89 (24%) had LLD and 278 (76%) had non-LLD. Within the RAS wt LLD and non-LLD subpopulations, demographic and baseline characteristics were comparable between the cetuximab + FOLFIRI and FOLFIRI treatment arms. In patients with RAS wt LLD, adding cetuximab to FOLFIRI significantly improved PFS (hazard ratio [HR][95% CI]=0.21[0.09-0.49])and ORR (odds ratio [OR][95% CI]=8.99[3.17-25.52]), and numerically improved OS (HR[95% CI]=0.65[0.38-1.10]) and R0 resection rate (OR[95% CI]=2.68[0.63-11.43]) relative to FOLFIRI alone. In patients with RAS wt non-LLD, adding cetuximab to FOLFIRI significantly improved PFS (HR[95% CI]=0.65[0.46-0.93]), OS (HR[95% CI]=0.71[0.54-0.93]), ORR (OR[95% CI]=2.44[1.49-3.98]), and – numerically – R0 resection rate (OR[95% CI]=5.94[0.79-44.88]). Similar results were obtained from the KRAS wt population. Conclusions Adding cetuximab to first-line FOLFIRI appears to improve clinical outcomes and R0 resection rates in KRAS wt and RAS wt mCRC patients with LLD, as well as in those with non-LLD.
ISSN:0748-7983
1532-2157
DOI:10.1016/j.ejso.2016.05.038