Transcript:Philip A. Philip, MD: We always have followed the NCCN guidelines. And, there are a number of reasons for that; but, the simple one is that the NCCN guidelines are produced by a group of leaders who try to look into a new drug, or a new treatment, or a new treatment strategy, and weigh the benefits versus the risks. It’s basically how much the patient benefits from it, so that’s something which is very important for us. In fact, that has been reviewed by the NCCN panel. They have put it as category 1, so that makes it an option that we have to consider. And it’s an option that is a standard of care and an option that a patient has to be offered as a treatment in this setting. And patients who have failed gemcitabine-based treatment have to be considered for a nanoliposomal irinotecan plus the 5-FU/leucovorin. That is evidence level 1, which makes it something that we must consider in those patients. There might be a patient in whom we cannot give the regimen, but that would be an exception, knowing about this regimen that is relatively well tolerated. And there aren’t that many things that we can think of that will preclude us from using the regimen. For example, if it is a treatment that causes neuropathy, then patients who have neuropathy cannot get it. But, it doesn’t do that.

When I treat patients with advanced pancreatic cancer, and they’re going through their treatments, I personally start the majority of patients with gemcitabine/nab-paclitaxel. And when they fail the treatment, usually by disease progression, they can’t continue on the treatment. So, my second-line option at this time, and it has been like this for a number of months now, is using the combination of nanoliposomal irinotecan plus 5-FU/leucovorin, which would be the same regimen that was used in the NAPOLI-1 study in patients with metastatic pancreatic cancer. Using a combination treatment in a second-line setting in advanced pancreatic cancer also means that you cannot apply the treatment unless the patient has favorable performance status, so we’re talking about 0, 1, and possibly 2. And I personally would use it in that category of patients. It’s hard for me to put an age limit at which I would not use the regimen, because to me, I’m more guided by performance status and organ function. But, as I mentioned earlier, I would also look into what the patient wants to have because patients have to be informed about how much benefit they get from the treatment and what they will be going through. So, some patients may not want to go on the combination of liposomal irinotecan and 5-FU/leucovorin. But, really I rarely come across patients who don’t want to get a combination treatment for reasons of performance status being an issue or quality of life. Normally, patients would be agreeable to go on a treatment like that. When I choose this regimen, performance status is my number-one determinant whether I go on this regimen. Because my other alternative is either to give them a single-agent fluoropyrimidine like capecitabine or 5-FU, or if their performance status is very poor, then I’m not really going to give them any chemotherapy. I’m just going to focus on supportive or palliative care. One thing I have to make sure that people are aware of is that the patients who come to us with pancreatic cancer, they are often symptomatic and their symptoms come from pain and weight loss, anorexia. They have malabsorption from the lack of pancreatic enzymes sometimes, but also they are affected psychologically. And it’s very important when we talk about treatment, whether it is frontline or even more importantly for second-line, is that we have to support the patients very well. Because, it’s okay for us to talk about chemotherapy, but chemotherapy, we know it affects the body. It affects tumor cells, but it also affects normal cells. And, therefore, we have to be also very aggressive in supporting the patients through chemotherapy. And that’s important, because that helps patients to feel better, or at least it minimizes the rate of the decline of their performance status or quality of life.

Tanios Bekaii-Saab, MD: So, we’ve treated a number of patients with MM-398 plus 5-FU in patients who failed gemcitabine/nab-paclitaxel. And our results reflect very much what was seen on the study. We’ve seen few responses. The study reports about 16%; I think about 1 out of 5 patients would have a response, or 1 out of 6. And, that’s pretty much what we’re seeing in the clinic. The toxicity profile is acceptable. We have a lot of experience with irinotecan-based regimens and other topoisomerase inhibitors. And, so, most of the toxicities are within the same level of toxicity. We’ve not seen anything unusual that wouldn’t be expected at this point of time. So, we have patients who responded and we have patients who did not respond. But, overall, the toxicity profile seems to be well tolerated. And, like I said, we have a lot of familiarity with this class of agents and there’s nothing unexpected at this point of time.

I’ll tell you about the last patient that I treated with 5-FU/MM-398. This was a patient that essentially presented a couple of years ago with metastatic pancreas cancer and went on gemcitabine/nab-paclitaxel, the every-other week regimen—so, the bi-weekly regimen as per our institutional standard. And the patient had a significant drop in the CA 19-9, the CT scan that shows a really nice response in the pancreas tumor and the patient had fewer liver lesions. Actually, one of them almost disappeared and the others shrunk. And the patient went a full 2 years on gemcitabine/nab-paclitaxel, which goes to tell you about the tolerability of this regimen, and then eventually progressed with multiple liver lesions, a little bit of ascites. So, you know that there were some peritoneal deposits. And the pancreas tumor grew I think about 20%. The patient was still in good performance status, with a performance status of 1. We discussed with the patient and eventually placed the patient on 5-FU and MM-398, so the nanoliposomal irinotecan. We had a scan. After 2 months, I saw the patient in clinic. He was feeling a little bit better, his belly was a little bit less swollen, the pain improved a little bit, and CA 19-9 dropped by about 50%. The pancreas tumor didn’t change in size, but the liver tumors all shrunk by about 20%. The patient continued on treatment and is still going on treatment at this time.

Transcript Edited for Clarity