Emerging Treatment Strategies in Advanced Pancreatic Cancer
At the ESMO Congress 2019, Eileen O'Reilly, MD, from Memorial Sloan Kettering Cancer Center, discussed the common themes among emerging therapies in the advanced pancreatic cancer setting.
So there are a lot of things in development in advanced pancreas cancer and I would say the big themes would be DNA repair, stromal modulation, metabolism, and where immunotherapy fits. And, so we have examples of positive studies in the DNA repair setting. Germline BRCA individuals who received FOLIFIRINOX or platinum-based chemotherapy who had stable or responding disease at 4 months as part of the POLO study had the option to be randomized to either olaparib or placebo. That was a positive trial in terms of its primary endpoint of [progression-free survival] PFS and a higher response rate also on the olaparib arm with some very durable responses. So that establishes the precedent that selected genomic targeting in pancreas cancer can work for a subset. We now need to amplify that signal and expand it to a broader population.
With regard to stromal modulation, a number of drugs have been developed. Hedgehog story is an old one where we saw negative to neutral signals in terms of outcome. The current big one is the PEGPH20, pegylated hyaluronidase enzyme, which is being looked with chemotherapy in advanced pancreas cancer and we’ll hopefully have data in the very near future to comment on that strategy.
And then metabolism is again an emerging theme, we don’t have late-stage study results yet, but a couple of examples would be eryaspase, which is being developed primarily here in Europe. It is an asparaginase compound that’s harbored in red blood cells and delivered in combination with chemotherapy. Randomized phase 2 presented at ESMO 2 years ago was positive and now that’s in phase 3 development. CPI-613, another metabolism agent is being evaluated in combination with modified FOLIFIRINOX in untreated advanced pancreas cancer. So a lot happening, and immunotherapy we’re still looking hard.