Also, we already know that antiangiogenic agents work for patients with gastric cancer, noting the approval of ramucirumab (Cyramza). We have also seen randomized phase II data that suggest that regorafenib may also be a potential option for these patients with gastric cancer, as well.
The other big question is, how about the combination of antiangiogenic agents and checkpoint inhibitors? We’ve seen some preliminary data of pembrolizumab (Keytruda) plus ramucirumab, and we are not quite sure how much it might benefit patients yet. It was very early data but, certainly, looking at those combinations as options for these patients is very exciting. What are your thoughts on stemness inhibitors?
One new class of drugs that people are very interested in are the stemness inhibitors. We know that, in general, chemotherapy will kill off the weaker cancer cells in a tumor. However, the stem cells are sort of the “king and the queen on the chess board” and are very chemotherapy-resistant, and are left to repopulate the cancer after chemotherapy. Targeting these stem cells is particularly interesting.
We have seen different stem cell inhibitors; one of them is called BBI-608, which is a STAT3 inhibitor. We have looked at it in combination with multiple chemotherapies across different tumor types, and we’ve certainly seen a lot of promising preliminary results that are being taken into larger trials right now.What does the safety profile look like of these types of agents?
So far, the primary toxicity we have seen with these cell-cycle inhibitors—particularly the STAT3 inhibitor—is diarrhea. However, this can be controlled by drug holds, dose reductions, and antidiarrheal medications. Does the STAT3 signaling pathway seem to be a promising target?
It’s too early to say about that. Finally, you lectured on the state of the science surrounding pancreatic cancer. What is new?
We have made a lot of progress in the last couple of years, in terms of the treatments of patients with advanced pancreatic cancer. We have regimens like gemcitabine/nab-paclitaxel (Abraxane) as well as FOLFIRINOX, which improves survival overall, but we certainly have a long way to go.
There are a number of agents currently in study, including agents like PEGPH20, which is trying to break down the stroma around the tumor. We know that, in pancreatic cancers in particular, there is a lot scar tissue, which makes it hard for chemotherapy drugs to get to the tumor. Ways to break down that scar tissue and potentially deliver the chemotherapy better is a very interesting way to look at treating patients with pancreatic cancer.
Certainly, we’re seeing trials with PEGPH20; we’ve seen data in the randomized phase II HALO-202 study with people who have high levels of hyaluronan in their tumors—it’s about 50% of patients with pancreatic cancer. When they’re treated with PEGPH20 in combination with chemotherapy compared with chemotherapy alone, we saw some preliminary results that suggest an improvement in PFS; that’s now in a randomized phase III study.
Another thing that people are trying to do is look at immunotherapy options for pancreatic cancer. Common checkpoint inhibitors pretty much don’t work across the board for pancreatic cancer in general. However, there are new agents in development including interleukin-10 (IL-10) agonists that activate T cells, as well as others. We have a lot of things going on right now in terms of research for pancreatic cancer. What are some other exciting ongoing trials in pancreatic cancer?
Another trial that is particularly interesting for patients with pancreatic cancer is using the stem cell inhibitor in combination with chemotherapy. There is a randomized phase III study in the works that is looking at gemcitabine/nab-paclitaxel with or without the stem cell inhibitor. We saw very interesting data in the phase I study, showing a lot of responses for patients with pancreatic cancer. Hopefully, that might translate to some benefits we can see in a phase III study. You were the chair of this State of the Science Summit. Why is it important for community physicians to attend?
It is so important to stay educated now in oncology. I don’t know how people do it who see all different types of tumors, because there is so much development going on and so many new FDA approvals. We just had another approval for patients with breast cancer. How can you keep track of it all? The educational events are great ways to do it, where you can actually be with folks who are treating those types of tumors specifically, and you really get a chance to hear the latest and greatest from them.