Emerging Approaches: Pancreatic Cancer Systemic Therapy - Episode 8
Transcript: Tanios Bekaii-Saab, MD: The whole concept of maintenance therapy I think is one of the most important concepts in oncology. The same with the sequencing consideration. Why? Because in a palliative setting, most of the patients we treat are in palliative setting, the primary goal remains palliation. I think oftentimes we forget that the primary goal is palliation. The secondary goal is overall survival.
Now, of course, everyone wants an improvement in survival and that’s important. But how do you reach it? Do you compromise the quality of life of your patients, I mean you make them so miserable that life is not even worth living sometimes? So we have to be careful, it’s a fine balance. So I’m a big proponent of maintenance therapy, and I’m a big proponent of sequencing strategies. Now what does maintenance strategies mean? Meaning that you go through what we call induction. Borrowed the term from our hematologic cancer colleagues. So you go with induction, and then you tone it down. And I think with FOLFIRINOX [fluorouracil/irinotecan/oxaliplatin] you, frankly, have value in the first 3 to 4 months of therapy. Beyond that point you’re primarily giving the patient more toxicities than benefit.
So I think the question of maintenance is very important, and that has been addressed in that PANOPTIMOX study, suggesting that actually there’s a role for maintenance treatment. So the way I would do it in clinic is I expose patients to the 3 to 4 months of FOLFIRINOX, those that I choose to start with FOLFIRINOX, which as I said, are few and far between, and those are the patients after 3 to 4 months if they have a response or they’re stable and maintain it after 4 months, I drop the oxaliplatin and go through a month or 2 of FOLFIRI [folinic acid/fluorouracil/irinotecan], and then if everything still looks good, I actually go to capecitabine and maintain them on capecitabine.
That strategy essentially allows patients to have enough exposure to the effective regimen, tone it down 1 notch, and then cruise them along with oral capecitabine. That seems to essentially maintain survival for those patients similar to if you just beat them with FOLFIRINOX. They won’t be able to go more than 6 months or 8 months of FOLFIRINOX. It’s rare to see a patient go beyond 6 months of FOLFIRINOX. And then you get the limitations of what do you do next. Patients are tired, have fatigue, cumulative toxicities. All this stuff. Survival may be about the same, but those patients are essentially miserable at that point. So the maintenance, now we have a study that tells us maintenance is a good strategy. It’s a reasonable strategy, and I think for all purposes should become part of our standard.
Davendra Sohal, MD, MPH: There’s an interesting question being explored at present: What should be the maintenance approach to pancreatic cancer? The comparison or the paradigm has been established in colon cancer. Unfortunately, in pancreatic cancer, the timelines are, in a sense, compressed; we don’t have effective salvage therapy options. The studies being conducted, as we speak, exploring maintenance options, consider a doublet after FOLFIRINOX or FOLFOX [folinic acid/fluorouracil/oxaliplatin], or drop the oxaliplatin because it can yield neuropathy and hypersensitivity.
The question still remains to be answered properly or finally. If this is a valid approach, there is some evidence now from the PANOPTIMOX trial that we could drop oxaliplatin and reduce the toxicity burden without compromising efficacy. But in the real world setting that is still probably a patient-by-patient discussion. FOLFIRINOX could be dialed down to FOLFIRI, for example; GEM [gemcitabine]/nab-paclitaxel can be dialed down to an every-other-week schedule, for example, or dropping nab-paclitaxel. But these are still dependent upon the patient’s progression in terms of functional status, as well as the disease status in terms of control and the division of control.
The POLO study is asking a very interesting question, the important question of maintenance olaparib use in pancreatic cancer. Pancreatic cancer, probably about 5% of cases have BRCA1/2 alterations. And about 15% to 17% of cases have the so-called BRCA-ness signature, which is deficient DNA repair alterations in many genes. One or more of many genes.
And the use of PARP [poly ADP ribose polymerase] inhibitors, namely olaparib being the primary one, is being investigated in the POLO study, akin to ovarian cancer where they showed excellent outcomes with maintenance use of olaparib after chemotherapy frontline in newly diagnosed ovarian cancer. Pancreatic cancer may also show similar results. The caveat is, however, that the ovarian cancer data were in germline BRCA1 and 2, which is a small proportion in pancreatic cancer. And, of course, the biology of the 2 diseases may be different, but it’s an important question. It is a significantly larger subset of actionable alterations if it pans out compared to, for example, microsatellite instability, which is barely 1%.
Transcript Edited for Clarity