Transcript: Shantal Ginsberg, RN: Since we have had the availability of nanoliposomal irinotecan, is there a different way that you choose therapy for patients?
Paul E. Oberstein, MD: Yes. I think this agent has definitely made a difference in how we approach patients. Nanoliposomal irinotecan was approved in combination with infusional 5FU [fluorouracil], similar to other regimens in which we combine an irinotecan base with 5FU. This was approved based on the clinical trial showing that it was superior to infusional 5FU alone for second-line metastatic pancreatic cancer patients. The benefit is quite variable. Like any chemotherapy regimen, there are some patients who benefit tremendously from it and some in whom it seems to cause more adverse events than benefit.
But like any chemotherapy regimen, it’s very difficult to know beforehand which category a patient is going to fall in. And so we obviously try to screen our patients very well, enroll patients appropriately, and use this agent in patients who are similar to patients enrolled on the clinical trial that led to its approval. And, of course, we monitor these patients very closely. The most important point is that having an option for second-line treatment in pancreatic cancer is a novel thing. There are no other agents currently that are approved for second-line therapy in pancreatic cancer, and that’s something that really makes a difference for many patients.
One of the challenges is that nanoliposomal irinotecan is only approved for patients who received gemcitabine-based chemotherapy in the first line. So, if a patient received FOLFIRINOX, they do not potentially benefit from this agent, given that it’s very similar to irinotecan, which is an agent in FOLFIRINOX. This is an option for patients. It’s really only an option for a select group of patients. In those patients who come to us already on first-line treatment, we obviously can’t make a change in what they’re getting on this basis. We often can modify or adjust their first-line treatment with the knowledge that we have a second-line agent waiting for us.
That knowledge is helpful. It’s helpful if we get some sign that chemotherapy is not working or if the toxicity of chemotherapy is building, but it’s also helpful in clinical trials. We learn from a large number of clinical trials to assess what other agents might work for second-line or third-line pancreatic cancer. And the availability of a control arm, a standard chemotherapy regimen that we can put up against our experimental arm, has been very helpful and is in use in many randomized clinical trials. We use now nanoliposomal irinotecan in those clinical trials as the standard of care. Of course, in a patient who doesn’t go on a clinical trial, we use it in those who have received gemcitabine as a standard second-line chemotherapy agent.
Shantal Ginsberg, RN: Can you speak to your personal experience about the efficacy of this and toxicity that some patients experience?
Paul E. Oberstein, MD: Absolutely. Clinical experience is quite variable because it depends on the number of patients a person sees and how well those patients are doing. In general, we try to give this chemotherapy agent to the most fit, strongest patients. There are some people who receive first-line chemotherapy, their disease progresses, and they have functional decline. They’re probably not strong enough to receive this chemotherapy agent. They’re not the best people to receive it for a couple of reasons. One is that they probably can’t handle the adverse events. And second of all, we probably will not keep them on it for long enough to get the clinical benefit.
So we try to select patients who we think will be able to remain on therapy for at least 3 months, which is the time we think a person should be on it to see the benefit, and who can tolerate the adverse events. The primary adverse events that we see with nanoliposomal irinotecan in combination with 5FU are diarrhea, low white blood cell count, increased risk of infection, and sometimes nausea that comes with these agents, among other side effects. But those are the major ones that we see. We evaluate patients very closely to determine whether we think they’ll be eligible for that and whether they can cooperate with the supportive care medications that will help them feel better.
Shantal Ginsberg, RN: How has the approval of nanoliposomal irinotecan to NYU affected your clinical decisions and experience?
Paul E. Oberstein, MD: I recently moved to NYU, but we recently added nanoliposomal irinotecan to our formulary and are using it regularly in appropriate patients at this point. This has given us a new option, and so it’s not a purely novel agent but it’s something that’s FDA approved and available for strong patients who are fit and able to receive chemotherapy. And I would say that we collect data about our patients. We don’t have a large enough number of patients to say that we’ve done our own clinical trial. But, in the patients who we’ve treated, there are many who received substantial benefit from this agent.
And, of course, it’s always difficult. It’s given in combination. Everyone has some adverse events, but we’ve seen that in general, if patients are selected carefully and they don’t have a lot of fatigue or a lot of diarrhea or gastrointestinal issues when they begin, they’re often able to handle the regimen. And we’ve seen several specific cases where patients who had multiple symptoms before they started, a rising CA 19-9, or clearly progressive pancreatic cancer, had responses to second-line therapy with nanoliposomal irinotecan plus 5FU.
Shantal Ginsberg, RN: Do you feel that you’ve had successful cases since using this? Can you talk about a specific example of what you consider a successful patient or result?
Paul E. Oberstein, MD: Absolutely. Success is really defined by whether it helps the patient. So, although we often measure things in clinical trials by numbers, response rate, and survival, we really want to know if a person who received this medication feels better than they would have felt had they not received it. And that’s difficult to assess because you don’t know what would have happened had you not given it.
But we really have, I think, a good number of patients who were receiving therapy for metastatic pancreatic cancer who were clearly declining. And by declining, I mean that there were markers in the blood as well as CT scans that showed their tumors were growing or a tumor was growing. But probably more importantly, the person was feeling worse. They had increased fatigue or increased pain, which are very common side effects of pancreatic cancer. And, in several patients, we’ve started them on nanoliposomal irinotecan plus 5FU and really seen results. We had a patient very recently who had 3 months of therapy and then had their CT scan, and the CT scan showed that their tumor had gotten substantially smaller in size. But perhaps much more importantly, the person felt better. They had less fatigue, more energy. They were eating better. And so clinically, this person was benefitting from this therapy and they will remain on therapy.
We’ve had other patients who had very similar responses where they had perhaps small tumors that didn’t necessarily change in size, but they were associated with biomarker benefit, meaning the CA 19-9 in the blood went down. And usually, the patients start feeling better or don’t have progressive decline in their symptoms.
Transcript Edited for Clarity