Advances in the Treatment of Pancreatic Cancer - Episode 12
John Marshall, MD: OK, why are you upset?
Shubham Pant, MD: I think as a pancreatic in a phase I, I’m an eternal optimist. That’s the first thing. I do think, exactly as Paul said, it was great getting all these patients accrued, so we really have to tip our hats to the investigators of the study. To get this scale of study done is amazing, and we need more studies like that in pancreatic cancer, in which we’re trying to find answers. I don’t think I was disappointed; I was hopeful for better results.
John Marshall, MD: On the overall side?
Shubham Pant, MD: On overall. When it said plenary—it’s coming out—I was excited. I was very excited about it. Maybe I should have tempered my enthusiasm just a little bit. I think the disease-free survival was 3.6 months’ improvement. That’s great for our patients, because I think we can give them a chemotherapy break and put them on this.
However, the tempering part was the overall survival. There was no overall survival benefit. Granted, there was a 15% crossover. Fifteen percent of patients did get a PARP inhibitor. But maybe in my mind, I looked at the ovarian data, and if you see those curves for overall survival, they are much further apart. When I looked at the overall survival curves this morning, that was a little disappointing to me.
That doesn’t take away from the fact that we need more studies like this to identify this patient population—screen 3000 patients, but find that 5% of these patients who can really benefit. I think it opens the door for further combination studies. How do you target it better, and where can we go from here? I’m very optimistic.
John Marshall, MD: Allyson, do you think this brings forward a new trial design in pancreatic cancer? I think this is very bold to have a placebo, no-treatment arm, even though it was 3-to-2 randomization and responders in frontline as maintenance. As not only an outstanding investigator but a patient advocate, what’s the take on that side?
Allyson Ocean, MD: I also think that’s the reason why it didn’t accrue so well. People in the BRCA community knew that they could get this off-label.
John Marshall, MD: You could get 1, right?
Allyson Ocean, MD: You could get 1 off-label. Why would I go on placebo?
John Marshall, MD: Even more evidence is that once you progress, they’re very hard to recapture. You need to kind of catch them while they’re down.
Allyson Ocean, MD: Right. To point out, though, remember that all the patients got 4 months of chemotherapy first. In the PARP arm, the survival time was over a year of disease, and the survival data were only less than half mature, so we may see something more come out of this.
Shubham Pant, MD: I’m hoping.
Allyson Ocean, MD: Yes, hopefully.
John Marshall, MD: It’s back to this predictive versus prognostic…
Allyson Ocean, MD: I feel that where the trial should go now, in this population, is, how can we harness the DDR [DNA damage response] pathway even more using combinations with chemotherapy and immunotherapy or even vaccines?
John Marshall, MD: As GI [gastrointestinal] oncologists, this is kind of a new drug class for us. I know our community partners use these things a lot, but they’re not all the same, and they’re not easy to combine with chemotherapy. It’s 1 of the reasons why these drugs are being isolated as single agents. They don’t really play well with some of our other drugs, so there are other ones to come in this space.
Paul Oberstein, MD: Even the patients who got placebo had a really good survival, and that sort of argues that maybe it is OK to stop everything, which is something I would have never done. I won’t call it a placebo.
John Marshall, MD: In this group.
Paul Oberstein, MD: In a group that’s BRCA-mutated that has done well, it might be safe to take 3 months off.
Allyson Ocean, MD: Right.
Shubham Pant, MD: That’s why we need randomized studies like this, which tell us exactly what the data are.
Transcript Edited for Clarity