Abstract
3513
Background: This trial evaluates the addition of C to our previously described treatment strategy of neoadjuvant chemotherapy before CRT and TME in patients with MRI selected high-risk operable rectal adenocarcinoma (Chua et al 2010). Methods: Eligible patients were randomised to 4 cycles of CAPOX followed by CRT (with concurrent capecitabine), TME and 4 cycles of adjuvant CAPOX (CAPOX) or the same regimen with weekly C (CAPOX + C). The primary endpoint was complete response (pCR or radiological CR in those not having surgery) in the KRAS + BRAF wild type (wt) population. Secondary endpoints included radiological response (RR), PFS, OS, safety and QoL. Molecular analysis was performed for PIK3CA, PTEN loss, EGFR and NRAS. Results: Between 2005-2008, 164 patients were recruited from 15 centres. Molecular analysis was performed on 149 patients, 90 (60%) had KRAS + BRAF wt tumours (CAPOX n=44, CAPOX +C n=46). In 15 patients, insufficient tissue was available for analysis, 8 of whom achieved a pCR. In the wt population the RR was significantly improved with the addition of C to neoadjuvant chemotherapy (50% vs 70% p=0.038) and CRT (72% vs 89% p=0.028). There was no significant difference in CR (9% vs 11%) or pCR (7% vs 11%). PFS curves separated at 1 and 2 years in favour of C but 3 year PFS was 81% vs 80% HR 0.81 p=0.668. There was a significant improvement in 3 year OS with the addition of C (81% vs 96%; HR 0.27, p=0.035). In the all treated population there was no difference in any of the endpoints. Skin toxicity was increased with C during neoadjuvant chemotherapy and CRT and diarrhoea was increased during CRT. Conclusions: The addition of cetuximab in wt patients significantly improved RR and OS. The low pCR rate may be explained by the 8 patients with a pCR but insufficient tissue for molecular analysis, 6 of whom received cetuximab. The high overall survival demonstrated in both arms, in this selected poor risk group supports further evaluation of neoadjuvant chemotherapy in rectal cancer. The molecular analysis of PIK3CA, PTEN loss, EGFR and NRAS will be presented at the meeting.
© 2011 by American Society of Clinical Oncology
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