At the European Society for Medical Oncology (ESMO) 2012 Congress in Vienna, David Ferry, Professor of Medical Oncology at New Cross Hospital in Wolverhampton, reported the results of the Cancer Oesophagus Gefinitib (COG) study, a UK 450 patient, multicenter, phase III clinical trial that looked at whether gefitinib (Iressa) could improve overall survival in esophageal cancer patients who had progressed after chemotherapy.
This is a disease for which there are no treatments that prolong life in the 2nd or 3rd line setting! Sadly, the trial results were negative; there was no difference in overall survival between the placebo and gefitinib study arms.
The results are shown in the graphic that Professor Ferry presented:
Placebo Arm (n=225): Median Overall Survival of 3.6 months
Gefitinib Arm (n=225): Median Overall Survival of 3.73 months
A non-significant difference. The data broken down by performance status shows:
- PS0 – median OS = 6.03M
- PS1 – median OS = 3.93M
- PS2 – median OS = 1.97M
That you might think is the end of the story, just another negative trial, another example of the natural selection that takes place in the development of new cancer treatments.
“Gefitinib in Esophageal Cancer – just the beginning of a spicy story”
was the title given to the presentation by Arnaud D. Roth, MD Chief of Oncosurgery at Geneva University Hospital who discussed Professor Ferry’s paper at ESMO 2012.
There are a subgroup of patients who respond
Dr Roth pointed out that there were a subgroup of patients in the COG trial who responded well to gefitinib and lived longer as a result. In the waterfall plot he presented, you can see the partial response highlighted.
Using crizotinib as an example, (it is effective in only 5.5% of NSCLC patients), Dr Roth challenged the audience as to why we couldn’t identify the subset of esophageal cancer patients who might respond well to gefitinib.
He noted that 50-70% of esophageal cancers overexpress EGFR protein, suggesting some basis for using an anti-EGFR agent such as gefitinib.
To define this subset of esophageal patients, “we need to go deeper into the biology of esophageal cancer,” Roth said.
- Do not lose too much time at looking for discreet mutations predicting response to gefitinib
- Analyze the responding subpopulation by genomic profiling and examine if they correspond to a particular subtype
- Validate findings in relatively small clinical studies
Dr Roth concluded that:
“Better knowledge in molecular biology in this disease might help to select patients who might benefit from anti-EGFR TKI’s”
In summary, while the COG trial showed that gefinitib does not improve overall survival in second or third line treatment of esophageal cancer, there is hope that in the future we may be able to identify those patients who might respond, and live longer as a result.