We presented results of a randomised phase II trial of SWOG 1505. We compared two perioperative chemotherapy regimens, modified FOLFIRINOX and gemcitabine nab-paclitaxel which are the standard front-line regimens for metastatic disease. This was the first study to test them in the perioperative setting for resectable pancreas adenocarcinoma. We found that of the 147 patients we enrolled with 102 eligible there was a 29% proportion of patients who were found to be ineligible on central radiology review. Of the 102 eligible patients 96% in each arm approximately started chemotherapy, 85% completed all chemotherapy and 73% and 70% reached surgical resection with the FOLFIRINOX and gemcitabine nab-paclitaxel arms respectively. The R0 resection rate among those who got resected was 85% and the primary endpoint of two year overall survival did not reach its pre-specified threshold. The median overall survival in each arm was about 23 months and it was not markedly different between the two arms.
So the take home point was that the study did not meet its pre-specified threshold of overall survival improvement but we had important lessons that we learned moving forward.
It was a randomised phase II trial. We treated patients with resectable pancreatic adenocarcinoma. They were enrolled and randomised to one of two arms – arm 1 was modified FOLFIRINOX and arm 2 was gemcitabine nab-paclitaxel. In each arm patients received three months of chemotherapy and then underwent restaging scans and after those restaging scans if there was no disease progression they underwent surgical resection. After surgical resection they then underwent three more months of adjuvant chemotherapy with the same regimen that they were assigned to at the beginning.
The number one lesson is that perioperative chemotherapy is safe and feasible for patients, 85% of them completed preoperative chemotherapy and 73% and 70% underwent resection. So we established safety. We also established metrics in this setting. The adjuvant chemotherapy trials for resectable pancreas cancer enrolled patients after resection and a lot of patients don’t even make it to that point. But in our study this was all comers, patients enrolled from day one of pancreas cancer, and we established metrics of outcomes in terms of overall survival, disease free survival and R0 resection with these modern chemotherapy regimens.
The third very important lesson we learned is that 29% of patients, for example in our study, had more than eligible disease for resectability criteria and therefore moving forward there has to be a lot of importance placed on quality control to ensure that we are, indeed, enrolling resectable disease in these studies.
Do you have any follow-up planned?
We are doing correlative studies to identify sarcopenia on baseline scans to assess whether that might be related to ultimate outcomes as well as detailed immunologic and immunohistochemical evaluations of surgical specimens to see if we might find predictors of response in terms of immune infiltrates into the tumour as well as pathologic complete response as it might related to overall survival outcomes.