Emerging Approaches: Pancreatic Cancer Systemic Therapy - Episode 6

Sequence Therapy & the Impact of Liposomal Irinotecan

Transcript: Davendra Sohal, MD, MPH: Sequencing treatments in pancreatic cancer is an interesting question. We honestly do not have a lot of options, unlike diseases like colon cancer, for example, that have a lot of time to sequence, and you can go back to salvage therapies. In pancreatic cancer, if we start with FOLFIRINOX, the second-line option would be gemcitabine and nab-paclitaxel per ASCO’s [the American Society of Clinical Oncology’s] guidelines in the perfect patient, so to speak. Again, this is not out of hard, randomized, controlled trial data, but based on the availability of regimens in this setting.

The second-line option for treatments of patients treated with gemcitabine and nab-paclitaxel in the first-line setting are 5-fluorouracil [5-FU] plus nanoliposomal irinotecan. This is supported by the NAPOLI-1 study randomized control trials. We have good data behind this option. So 5-fluorouracil plus oxaliplatin per ASCO’s guidelines is an acceptable alternative, although with the caveat that there were 2 conflicting studies—1 showing support of 5-fluorouracil oxaliplatin, namely FOLFOX, and 1 going against it. So it is a softer recommendation per ASCO.

Tanios Bekaii-Saab, MD: With all different types of cancers, one thing we learned, and we learned that it is a very important aspect of how we treat patients, is the capacity to sequence therapies. Why is this important? Because when you expose more patients to more treatment over time, we know that that is likely to improve outcomes. And outcomes, definitely survival, but also think about quality of life. I mean, those patients who get exposed to modified FOLFIRINOX, some can fly through it fine, but it’s a rough regimen. And for many patients, they drop out early, with significant toxicities. It’s a tough one, plus it eliminates a lot of patients who are older, which is the bulk of patients who get pancreatic cancer.

With the introduction of nanoliposome, irinotecan and 5-FU, we get an option that allows us to think a little bit differently about first line. Now liposomal irinotecan and 5-FU on the NAPOLI-1 study suggested an improvement in outcome versus 5-FU with survival PFS [progression-free survival], and even a response rate reported at least first at 16%, and with 5FU at 1%. So we know that there is something going on there.

This was in patients who failed gem, prior gemcitabine. The problem with FOLFIRINOX is, in addition to being tough on patients, and many patients not able to continue through, it also limits our second-line options. So a lot of these patients end up progressing, they don’t have real good second-line options. Some folks use gemcitabine and nab-paclitaxel based on almost no data except some small studies here and there with respective analysis. But there’s also the capture of toxicities. A lot of these patients have neuropathy, their bone marrows are tired, they can’t really go on gemcitabine and nab-paclitaxel. So we limit options.

With a more rational, I think, sequencing approach with the availability of nanoliposomal irinotecan in the second line, it allows us to think a little bit more rationally. Now we go with gemcitabine and nab-paclitaxel in the first-line, and then in second-line nanoliposome irinotecan plus 5-FU. So it creates now the second-line option that allows us to think about toning down the treatment a little bit and allow the patients to stay on treatment longer, but think about it as a longer continuum of treatment rather than just throwing the whole gauntlet at them.

Now I say that works for probably 80%-plus of the patients. But the other, I think, 10% to 20%, having a BRCA mutation or a PALB2 mutation, or maybe the DDR, although we still need to understand what DDR means for pancreatic cancer. Those are the patients who may benefit better from FOLFIRINOX for now, FOLFIRINOX rather than the other sequence. But think about it. For 80% plus of your patients who probably don’t need to be exposed to FOLFIRINOX, and they would be better off going through the sequence.

Davendra Sohal, MD, MPH: Nanoliposomal irinotecan has now been FDA approved for the use of second-line therapy, for the use in the second-line therapy of patients with pancreatic cancer, especially as a doublet with 5-fluorouracil for patients treated previously with gemcitabine-based regimens, practically gemcitabine, nab-paclitaxel. A nanoliposomal irinotecan can also be used alone by itself in the second-line setting if a doublet is too onerous for the patient based on functional status or comorbidities.

Transcript Edited for Clarity