In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 3537-3537
Abstract:
3537 Background: The OPUS study showed that the addition of cetuximab to infusional 5-fluorouracil/folinic acid + oxaliplatin (FOLFOX4) significantly improved progression-free survival (PFS) and response in the first-line treatment of patients (pts) with KRAS wild-type (wt) mCRC. High level expression in tumors of ERCC1, a protein involved in nucleotide excision repair, has been associated with resistance to platinum-based chemotherapy in a range of tumor types. This analysis assessed outcome according to ERCC1 expression level and treatment group in OPUS study pts. Methods: ERCC1 expression level was assessed by immunohistochemistry (IHC) in all available formalin-fixed paraffin-embedded tumor samples from OPUS study pts. An ERCC1 IHC score on a continuous scale of 0–300 was calculated for each tumor, based on the intensity of nuclear staining and proportion of positive cells. The median IHC score was used to define low ( 〈 median) and high (≥median) ERCC1 expression levels and outcome was assessed in low vs high expression groups in both treatment arms. Results: Of 337 OPUS study intention to treat pts, 97 (29%) were evaluable for ERCC1 expression. Pts in the FOLFOX4 arm in the high ERCC1 expression group (n=27) had shorter PFS (median 5.8 vs 9.2 months; hazard ratio, HR 1.63, 95% CI 0.80–3.34) and overall survival (median 11.5 vs 18.5 months; HR 1.75, 95% CI 0.90–3.40) and a lower response rate (33.3% vs 39.1%) compared with those in the low ERCC1 expression group (n=23). To assess the effect of adding cetuximab to FOLFOX4 according to ERCC1 expression level, outcome was assessed in the KRAS wt subgroup of pts. Although low pt numbers precluded the drawing of definitive conclusions, PFS in the high ERCC1 expression group was longer in the FOLFOX4 + cetuximab arm (n=14) compared with the FOLFOX4 arm (n=13; median 7.7 vs 5.8 months), survival was longer (median 19.7 vs 12.0 months) and the response rate was higher (71.4% vs 30.8%). Conclusions: High tumor ERCC1 expression was associated with poor outcome in pts with mCRC receiving first-line platinum-based chemotherapy. The addition of cetuximab to FOLFOX4 may mitigate this effect in those with KRAS wt tumors. Clinical trial information: NCT00125034.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2013.31.15_suppl.3537
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2013
detail.hit.zdb_id:
2005181-5
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