Meet The Professors: Pancreatic Cancer Edition, 2016 - Video 7NAPOLI-1 trial of nal-IRI with fluorouracil and folinic acid in mPAC
2:30 minutes.
TRANSCRIPTION:
DR LOVE: Any comments about this NAPOLI-1 study, the Phase III trial that led to the approval? We’ve been talking about it, but here’s the actual design. DR BEKAII-SAAB: Yes. And I think it’s very important to understand the design, historically. This started as a 2-arm study with nal-IRI at 120 mg/m2 every 3 weeks versus 5-FU. And the choice of the 5-FU was the weekly regimen, which is taken out of the CONKO study, the European study that compared OFF, so oxaliplatin and 5-FU and then the third arm with nal-IRI at a lower dose, 80 mg/m2, plus 5-FU/leucovorin given every other week. Notice that here, a bolus 5-FU was skipped. There was no bolus 5-FU in the regimen, which may explain some of the improvement in the toxicities. And so what this study essentially showed, just in a nutshell, that when you actually combined the nal-IRI with 5-FU, you have an improved survival and improved progression-free survival versus 5-FU alone. Interestingly, when you actually look at the nal-IRI alone — so the irinotecan, nanoliposomal irinotecan, agent alone — versus 5-FU, there wasn’t a difference in survival or PFS. Maybe a little trend, but really not significant. So it seems that you really need to combine the two to get a benefit, which is very similar, by the way, to colorectal cancer, where there is data that suggests that FOLFIRI is better than irinotecan, even when you fail 5-FU. So anyways, the 1 thing that I find very interesting about this study is that there was a reported 16% response rate in the second and third line, which is something that’s unusual in pancreas cancer — 1% response rate with 5-FU. So that’s a real differential in response rate which again, in second-line pancreas cancer, is very unusual. So I think there is this added potential historical benefit. And the toxicities are very similar to what you would expect with irinotecan-based regimens. It is interesting when you look at the diarrhea — it’s actually higher with the monotherapy than with the combination. And that has to do with the fact that it was a 120 versus 80 dose, not as much. So it has to do with the dose rather than with the frequency administered. And everything else seemed to be relatively similar. |