BARCELONA—In preliminary results, adding cetuximab to gemcitabine/oxaliplatin (GEMOX) chemotherapy resulted in disease control among two thirds of patients with advanced biliary cancer, according to a Phase II study reported here at the ESMO World Congress on Gastrointestinal Cancer.
Éveline Boucher, MD, of Centre Eugene Marquis in France presented the data from the open-label study of 101 patients who had not already received palliative treatment for their advanced biliary cancers and had a World Health Organization Performance status of 0-1.
Patients in both arms of the study were treated every two weeks with gemcitabine—1,000 mg/m2 (10 mg/m2/min) on Day 1—plus oxaliplatin (100 mg/m2) on Day 2. Patients in the investigational arm also received the anti-epidermal growth factor receptor agent cetuximab (at 500 mg/m2 at Day 1 or Day 2) every two weeks.
Dr. Boucher stressed that the results are from only 36 patients so far and are only preliminary. Still, “it seems there is an increase of efficacy in the cetuximab arm. We have a disease control rate of over 70%, which is quite unusual in this cancer.”
The primary endpoint was progression-free survival at four months (with the treatment considered ineffective if that rate was less than 40% and considered effective if more than 60%). Secondary endpoints were toxicity, response, disease control, overall survival, and resectablity.
Severe toxicity—neutropenia, GI toxicity, and rash—occurred only in the cetuximab group. Efficacy analysis was done after the first 36 patients, with a median follow up of 13 months. The goal was met in the investigational arm, with a four-month progression-free survival rate of 61%. At a median 6.5 months of follow-up, progression-free survival time was five months for the GEMOX group and seven months for those also receiving cetuximab.
The study has now been extended to include150 patients, and the researchers will assess the predictive and prognostic value of KRAS mutation and the relationship between treatment efficacy and tumor location.
Sufficient Statistical Power?
Asked during the question-and-answer period if the Phase II data had sufficient statistical power to confirm cetuximab's efficacy, Dr. Boucher acknowledged that that wasn't the case with the low number of patients so far, but that she looked forward to the results from the expanded study. In addition, she said, a Phase III study is also being considered.
Someone else asked why it was necessary to extend the trial to 150 patients, since wouldn't a Phase III study necessitate closing the Phase II investigation? “We think that with 50 more patients we will perhaps find a big difference between the two groups and see that cetuximab is effective,” she said.
As for whether cetuximab added to GEMOX could be considered a new standard of care, Dr. Boucher said, “Perhaps it could be, but this would require “a high level of proof.”
In an interview after her presentation Dr. Boucher noted that she and her colleagues will be assessing the relevance that molecular markers of outcome (such as KRAS mutation) have on the response to cetuximab—“We are going to analyze for EGFR expression, EGFR number of copies, and KRAS mutation, and correlate responses.”