Alfredo Carrato, MD, PhD, on Pancreatic Cancer: Nab-Paclitaxel, Gemcitabine, and FOLFOX for Metastatic Disease

It's a pleasure for me to show the results of the SEQUENCE trial. The SEQUENCE trial was a randomized phase two trial in pancreatic cancer patients, metastatic ones on first line and we tried to increase the efficacy of the regimens used for treating these patients. So the rational that there were two subtypes of pancreatic cancer, the basal one responded better to Nab-Paclitaxel Gemcitabine and the classical one better to FOLFIRINOX. So as it was impossible to give both regimens at the same time for toxicity issues, we decided to give them sequentially first Nab-Paclitaxel Gemcitabine, and then not FOLFIRINOX, FOLFOX because we thought that the oxaliplatin was the main drug of the combination. And on top of that, we had that Nab-Paclitaxel was given up front and it was depleting this trauma and allowing the drugs to get in touch more efficiently with the tumor cells. So we performed a phase I trial, and we were surprised because we were expecting some neurological toxicity, but no neurologic toxicity appeared and it was safe at full doses and it was published at the European General Cancer two years ago. Then we designed this randomized phase two trial, trying to increase 50% the survival of patients at one year. It was from 35% to 50%, more or less. So with these things in mind, we designed a trial in which 78 patients per arm were needed and the safety results showed that neutropenia and thrombocytopenia were higher in the experimental arm, significantly higher, 47% and 26% and the efficacy at 12 months hypothesis was met. We found that 55.5% of patients were alive at one year in the experimental arm and only 35% in the control arm, which was Nab-Paclitaxel and gem without FOLFOX. So we looked for other efficacy parameters, like time to progression free survival, overall survival, and all of them were positive. In favor of the experimental arm. We reached a median overall survival of 13.2 months versus 9.5 months in the control arm. The hazard ratio was lower to 0.65 and this was real good surprise because we have discovered a new treatment option for our patients and pancreatic cancer patients have few good news. In the last 20 years, just two trials demonstrated an increase in efficacy rates. One of them was the Nab-Paclitaxel Gemcitabine and now against this regimen, we have demonstrated a superiority in efficacy. So we are happy about that and because our patients will live longer and have another option for treatment. This is only for a core zero and one patients, it's only for well fit patients, not for performance status, middle, core two, or very old patients but when you have these patients, this regimen provides excellent results.