Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial
- Authors
- Sclafani, F.[Sclafani, F.]; Kim, T.Y.[Kim, T.Y.]; Cunningham, D.[Cunningham, D.]; Kim, T.W.[Kim, T.W.]; Tabernero, J.[Tabernero, J.]; Schmoll, H.J.[Schmoll, H.J.]; Roh, J.K.[Roh, J.K.]; Kim, S.Y.[Kim, S.Y.]; Park, Y.S.[Park, Y.S.]; Guren, T.K.[Guren, T.K.]; Hawkes, E.[Hawkes, E.]; Clarke, S.J.[Clarke, S.J.]; Ferry, D.[Ferry, D.]; Frodin, J.-E.[Frodin, J.-E.]; Ayers, M.[Ayers, M.]; Nebozhyn, M.[Nebozhyn, M.]; Peckitt, C.[Peckitt, C.]; Loboda, A.[Loboda, A.]; Watkins, D.J.[Watkins, D.J.]
- Issue Date
- 2017
- Publisher
- Wiley-Liss Inc.
- Keywords
- cetuximab; chemorefractory colorectal cancer; dalotuzumab; EREG; IGF-1; IGF-1R; IGF-2; KRAS exon 2 mutation
- Citation
- International Journal of Cancer, v.140, no.2, pp.431 - 439
- Indexed
- SCIE
SCOPUS
- Journal Title
- International Journal of Cancer
- Volume
- 140
- Number
- 2
- Start Page
- 431
- End Page
- 439
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/30930
- DOI
- 10.1002/ijc.30453
- ISSN
- 0020-7136
- Abstract
- Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, randomised, phase II/III study of irinotecan and cetuximab plus dalotuzumab 10 mg/kg once weekly (arm A), dalotuzumab 7.5 mg/kg every second week (arm B) or placebo (arm C). Objective response rate (5.6% vs. 3.1% vs. 4.8%), median progression-free survival (2.7 vs. 2.6 vs. 1.4 months) and overall survival (7.8 vs. 10.3 vs. 7.8 months) were not statistically significantly different between treatment groups. Most common grade ≥3 treatment-related toxicities included neutropenia, diarrhoea, hyperglycaemia, fatigue and dermatitis acneiform. Expression of IGF-1R, IGF-1, IGF-2 and EREG by quantitative real-time polymerase chain reaction was assessed in 351 patients from the same study with available data on KRAS exon 2 mutational status. Median cycle threshold values for all biomarkers were significantly lower (i.e., higher expression, p < 0.05) among patients with KRAS wild-type compared to those with KRAS exon 2 mutant tumours. No significant changes were found according to location of the primary tumour with only a trend towards lower expression of IGF-1 in colon compared to rectal cancers (p = 0.06). Albeit limited by the small sample size, this study does not appear to support a potential role for anti-IGF-1R agents in KRAS exon 2 mutant CRC. Data on IGF-1R, IGF-1 and IGF-2 expression here reported may be useful for patient stratification in future trials with inhibitors of the IGF pathway. © 2016 UICC
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