Pancreatic Cancer Upfront Therapy

Transcript:Philip A. Philip, MD: The most important factor that we use in deciding on up-front treatment is the performance status of the patient and how active they are during the 24-hour day. Using the traditional way of assigning performance status to patients is very important; it helps us in two ways. For one, it avoids giving a toxic treatment to somebody who will not be able to tolerate the therapy. And two, we also know that patients who have better performance status respond better. In terms of giving combination chemotherapy that we’re doing now, the role of the performance status is very important.

There are other factors I take into account, such as age. Patients who are older, especially over the age of 70 or 75, their tolerance to treatment will be less than those who are younger. And some regimens might work better in terms of tolerance, or even efficacy, if we choose the patients correctly. The median age of patients with pancreatic cancer in the Medicare registry and other registries is 71. Half of the patients we see are over the age of 70. Other factors, in addition to the performance status of the patient, might include the liver function test, for example; that’s very important.

One of the things in my practice that is also important is the patient preference. Because when I see a patient and we talk about treatment that is not curative, it’s palliative. It’s very important for us to talk to the patient about what to expect from the treatment: the benefits, risks, and side effects. And the patient is involved in deciding which treatment will work best for them. I have my recommendations, but the patient also has the chance to go over the recommended options and be able to make a decision on which one they want to pursue. One of the things that was successful in colon cancer was to do longitudinal treatment plans, which means that we are giving the patient the option of going on one treatment but also having a back-up or a second-line treatment if the first-line treatment does not work. In colon cancer, we manage to double, triple, or quadruple the survival rate because of the exposure of these patients to multiple lines of treatment. When you do that, you have a strategy for the patient, and which drugs you want to use in sequence depend on what you have. The availability of the nanoliposomal irinotecan (MM-398) with the 5-FU (5-fluorouracil) helps us to think of how to design a strategy, which is something that’s happening for the first time. Remember, this regimen is the only regimen that’s FDA-approved for second-line treatment, so now we have a firm strategy that we can apply to patients. In this respect, the nanoliposomal irinotecan—based regimen includes 5-fluorouracil. Certainly, it’s a good regimen to use after non–5-FU-based treatments in the frontline treatment. The clinical trial, NAPOLI-1, involved patients who had frontline gemcitabine-based therapy. When they were failing the treatment, they went on the nanoliposomal irinotecan plus the 5-FU treatment.

Tanios Bekaii-Saab, MD: In terms of selecting or finding selection strategies that would tell us which patient should get what regimen—which patient would be given gemcitabine/nab-paclitaxel, which patient would get FOLFIRINOX, or, rarely, which patient would qualify for gemcitabine—there are no good predictors or anything that would help us predict what patient falls into the particular basket. These agents, other than gemcitabine alone compared to FOLFIRINOX or gemcitabine/nab-paclitaxel and gemcitabine/nab-paclitaxel and FOLFIRINOX, have never been compared head-to-head, so we don’t know the differences between the two when we put them head-to-head.

Historically, FOLFIRINOX seems to have a higher response rate, a higher survival. Gemcitabine/nab-paclitaxel, although better than gemcitabine, historically has not shown the same level of response. However, it is very dangerous to actually do these historical comparisons because they’re completely different patient populations. In fact, we can argue that the gemcitabine and nab-paclitaxel study that included patients with poorer performance status was also conducted in countries that may not have access to second-line therapies; it’s very difficult to do the comparisons. There’s a study mostly observational, from the US Oncology Group that looked at the data in 1000 patients, and what they found is whether you start with gemcitabine/nab-paclitaxel or FOLFIRINOX, ultimately, you achieve the same survival, which essentially means that a doublet or a triplet induced the same level of survival. Although one may have a little bit higher response rate, ultimately, the goal standard is survival.

And I do believe when we look at other cancers—gastric cancer, colon cancer, breast cancer—what makes more sense is to essentially go to doublets or even singlets sometimes and just learn how to sequence regimens that are available to us, rather than to throw everything in one basket, the kitchen sink approach. Using the kitchen sink approach when you have multiple lines of therapy that are active doesn’t make sense. Essentially, by sequencing, rather than doing that whole kitchen sink approach, you reduce the risk of toxicity, and you induce about the same benefits in patients. Now that we have nanoliposomal irinotecan plus 5-FU or MM-398 plus 5-FU—that has shown activity and a good placing in the second-line versus 5-FU—one could argue that rather than use a triplet, which is highly toxic, FOLFIRINOX in the first-line, use a more rational doublet, followed by a doublet approach in patients who may be eligible for it, with less toxicities and induce the same results. Other than clinical selection right now, meaning that patient enters through the door, you assess their performance status and you decide on what regimen they may be end up being on. We don’t have any other way to select those patients.

Transcript Edited for Clarity