TY - JOUR
T1 - Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer
AU - Elez, E.
AU - Hendlisz, A.
AU - Delaunoit, T.
AU - Sastre, J.
AU - Cervantes, A.
AU - Varea, R.
AU - Chao, G.
AU - Wallin, J.
AU - Tabernero, J.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - © 2016 Cancer Research UK. All rights reserved. Background:This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC).Methods:Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m -2, folinic acid 400 mg m -2, and 5-fluorouracil (400 mg m -2 bolus then 2400 mg m -2 over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate.Results:Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8-77.6); complete response was observed in four patients; median duration of response was 10.0 months (7.0-16.0). Median overall survival (OS) and progression-free survival (PFS) were 22.5 (11.0-30.0) and 10.0 months (7.0-12.0), respectively. Clinical outcome was better in patients with KRAS exon 2 wild type (median OS 30.0 months (23.0-NA); median PFS 12.0 (8.0-20.0)), compared with KRAS exon 2 mutant tumours (median OS 7.0 months (5.0-37.0); median PFS 7.0 (4.0-18.0)). The most common grade ≥3 adverse events were neutropenia (29.5%), asthenia (27.3%), and rash (20.5%).Conclusion:First-line necitumumab+mFOLFOX6 was active with manageable toxicity in locally advanced or mCRC; additional evaluation of the impact of tumour RAS mutation status is warranted.
AB - © 2016 Cancer Research UK. All rights reserved. Background:This single-arm phase II study investigated the EGFR monoclonal antibody necitumumab plus modified FOLFOX6 (mFOLFOX6) in first-line treatment of locally advanced or metastatic colorectal cancer (mCRC).Methods:Patients received 800-mg intravenous necitumumab (day 1; 2-week cycles), followed by oxaliplatin 85 mg m -2, folinic acid 400 mg m -2, and 5-fluorouracil (400 mg m -2 bolus then 2400 mg m -2 over 46 h). Radiographic evaluation was performed every 8 weeks until progression. Primary endpoint was objective response rate.Results:Forty-four patients were enrolled and treated. Objective response rate was 63.6% (95% confidence interval 47.8-77.6); complete response was observed in four patients; median duration of response was 10.0 months (7.0-16.0). Median overall survival (OS) and progression-free survival (PFS) were 22.5 (11.0-30.0) and 10.0 months (7.0-12.0), respectively. Clinical outcome was better in patients with KRAS exon 2 wild type (median OS 30.0 months (23.0-NA); median PFS 12.0 (8.0-20.0)), compared with KRAS exon 2 mutant tumours (median OS 7.0 months (5.0-37.0); median PFS 7.0 (4.0-18.0)). The most common grade ≥3 adverse events were neutropenia (29.5%), asthenia (27.3%), and rash (20.5%).Conclusion:First-line necitumumab+mFOLFOX6 was active with manageable toxicity in locally advanced or mCRC; additional evaluation of the impact of tumour RAS mutation status is warranted.
KW - EGFR
KW - KRAS
KW - advanced colorectal cancer
KW - modified FOLFOX6
KW - necitumumab
UR - https://www.scopus.com/pages/publications/84954348380
U2 - 10.1038/bjc.2015.480
DO - 10.1038/bjc.2015.480
M3 - Article
SN - 0007-0920
VL - 114
SP - 372
EP - 380
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -
