George Kim, MD:The patient begins to show signs and symptoms that he had very early on before we began chemotherapy and before he benefited. We want to assess and restage the patient. Typically, we will use CAT scans with IV contrast and oral contrast. Sometimes we’ll use a PET scan to see the extent of whether the tumor has grown. Sometimes we’ll use CA 19-9. That’ll tell us if it’s increasing, that maybe we want to perform restaging studies earlier. We don’t want to make treatment decisions, make changes in our chemotherapy based on CA 19-9 alone. That is not sufficient, especially when you think about, again, this issue of managing the jaundice, the biliary stent. Because, CA 19-9 can falsely elevate in that situation.
Our patient presents with an increase in fatigue, changes in his appetite, pain, and the jaundice, and so we’re quite concerned about having tumor progression. And as we said, he goes on to have imaging studies that confirm that the liver lesions are progressing, and the mass and the pancreas is also growing. And so, now we have to think about changing our treatment strategy, our treatment.
In this setting, in the second-line, we have several options. Remember, we gave this patient gemcitabine/Abraxane. We know that when patients are treated with gemcitabine-based therapy in the frontline, we can go on to 5-FU-based therapy, and this is following the NCCN guidelines. So, our patient was treated with gemcitabine/Abraxane, and now we can go to 5-FU-based treatments. Now, there is an FDA-approved regimen that is available for our patients. This is a regimen using continuous infusion 5-FU, and combining it with a novel drug, ONIVYDE, or MM-398. It is a nanoparticle irinotecan liposome injection. This was studied in a trial, the NAPOLI-1 study, and when combined with 5-FU continuous infusion, and leucovorin, the drug and the combination showed a 2-month survival advantage. And so, it’s very important for people to realize that this drug is FDA-approved for gemcitabine-refractory patients. So, our objective continues to be to prolong time, maintain quality of life, and manage very closely the side effects from our intervention, but also the side effects from pancreas cancer itself. We will continue on to this second-line treatment.
If we had chosen FOLFIRINOX in the frontline setting, what we can use now in the second line is somewhat limited. We could try to give gemcitabine/Abraxane, but FOLFIRINOX carries with it oxaliplatin, which carries with it neuropathy, which is not necessarily reversible. And so, now you try to treat with another combination that has neuropathy associated with it. It’s very hard to go from FOLFIRINOX to gemcitabine/Abraxane. You would not use FOLFIRINOX in the frontline setting and then go to nanoparticle irinotecan liposome, or ONIVYDE. That doesn’t make a lot of sense.
So, that’s why when we talked about the treatment options for our patient in the frontline, we’re thinking about our treatment spectrum. What are we going to use if and when the patient’s tumors grow? What do we use in the second line? The gemcitabine/5-FU-based sequence, gemcitabine/Abraxane, has a survival advantage and is FDA approved. ONIVYDE, or the nanoparticle irinotecan liposome regimen, again, has survival benefit and is FDA approved. That’s why that sequence is so meaningful for our patients.
Transcript edited for clarity.