NEW YORK (Reuters Health) – A multicenter center study has shown that adding cetuximab to neoadjuvant chemotherapy and radiotherapy improves overall survival after excision of high-risk rectal cancer.
However, it does not improve complete response rates, according to a report online April 2nd in the Journal of Clinical Oncology.
While the results confirmed the efficacy of neoadjuvant chemotherapy in the treatment of high-risk localized rectal cancer, the authors say “we do not currently recommend the routine use of cetuximab in this patient population.”
Dr. David Cunningham, with the Royal Marsden Hospital in Sutton, Surrey, UK, and colleagues note that cetuximab is a potent radiosensitizer, and they explain that they previously conducted a phase II trial that demonstrated the feasibility of administering neoadjuvant oxaliplatin and capecitabine (CAPOX) before chemoradiotherapy and total mesorectal excision in patients with poor-prognosis rectal cancer.
In the current study they examined the benefit of adding weekly cetuximab to the CAPOX course in that protocol. Their analysis focused on 90 patients with KRAS/BRAF wild-type rectal tumors, which are likely to be susceptible to anti-EGFR therapy.
The primary endpoint of a complete response was not significantly different with or without cetuximab added to CAPOX (11% vs 9%), the investigators report. Also, progression-free survival was similar in the two groups (hazard ratio 0.65; p=0.363).
Cetuximab did improve some secondary measures, however. The radiologic response rates in the two arms were 71% vs 51% (p=0.038) after the neoadjuvant chemotherapy course and 93% vs 75% (p=0.028) after preoperative chemoradiation.
Furthermore, cetuximab was associated with better overall survival, with a mortality hazard ratio of 0.27 (p=0.034), Dr. Cunningham and colleagues report.
They conclude, “On the basis of these results, there are sufficient data to indicate that cetuximab has some biologic activity in this setting, and further evaluation in combination with alternative chemotherapy backbones may yield more promising results.”
The study was funded by the National Institute for Health Research Biomedical Research Center, the Pelican Cancer Foundation, and the Peter Stebbings Memorial Charity. Merck provided a research grant and cetuximab and Roche provided capecitabine; the authors say neither company was involved in the design or analysis of the study.
J Clin Oncol 2012.