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Relevance of liver‐limited disease in metastatic colorectal cancer: Subgroup findings of the FIRE‐3/AIO KRK0306 trial
Author(s) -
Holch Julian Walter,
Ricard Ingrid,
Stintzing Sebastian,
Fischer von Weikersthal Ludwig,
Decker Thomas,
Kiani Alexander,
VehlingKaiser Ursula,
AlBatran SalahEddin,
Heintges Tobias,
Lerchenmüller Christian,
Kahl Christoph,
Kullmann Frank,
Scheithauer Werner,
Scholz Michael,
Müller Sebastian,
Link Hartmut,
Rost Andreas,
Höffkes HeinzGert,
Moehler Markus,
Lindig Reinhard Udo,
MillerPhillips Lisa,
Kirchner Thomas,
Jung Andreas,
von Einem Jobst Christian,
Modest Dominik Paul,
Heinemann Volker
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31114
Subject(s) - medicine , bevacizumab , cetuximab , folfiri , hazard ratio , colorectal cancer , oncology , irinotecan , capecitabine , subgroup analysis , cancer , gastroenterology , confidence interval , chemotherapy
In metastatic colorectal cancer (mCRC), liver‐limited disease (LLD) is associated with a higher chance of metastectomy leading to long‐term survival. However, limited data describes the prognostic and predictive relevance of initially unresectable LLD with regard to targeted first‐line therapy. The present analysis investigated the relevance of initially unresectable LLD in mCRC patients treated with targeted therapy against either the epidermal growth factor receptor (EGFR) or vascular epithelial growth factor (VEGF). The analysis was performed based on FIRE‐3, a randomized phase III trial comparing first‐line chemotherapy with FOLFIRI plus either cetuximab (anti‐EGFR) or bevacizumab (anti‐VEGF) in RAS wild‐type (WT) mCRC. Of 400 patients, 133 (33.3%) had LLD and 267 (66.8%) had non‐LLD. Median overall survival (OS) was significantly longer in LLD compared to non‐LLD patients (36.0 vs . 25.4 months; hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.51–0.87; p = 0.002). In a multivariate analysis also including secondary hepatic resection as time‐dependent variable, LLD status was independently prognostic for OS (HR = 0.67; 95% CI: 0.50–0.91; p = 0.01). As assessed by interaction tests, treatment benefit from FOLFIRI plus cetuximab compared to FOLFIRI plus bevacizumab was independent of LLD status with regard to objective response rate (ORR), early tumour shrinkage ≥20% (ETS), depth of response (DpR) and OS (all p > 0.05). In conclusion, LLD could be identified as a prognostic factor in RAS‐WT mCRC, which was independent of hepatic resection in patients treated with targeted therapy. LLD had no predictive relevance since benefit from FOLFIRI plus cetuximab over bevacizumab was independent of LLD status.