George P. Kim, MD: Impact of Effective Therapies on Treatment

How has the availability of effective therapies shifted the treatment paradigm for patients with pancreatic cancer?

The recent approval of drugs for pancreas cancer has made us think about the sequence or the strategy of how we’re going to treat patients. So recently Onivyde and then 398 were approved. Again, that’s the nanoparticle liposomal irinotecan. We’ve had 2 other standard regimens, that being FOLFIRINOX and abraxane, nab-paclitaxel, and gemcitabine available to us in the frontline. So how do we use all of those treatments in terms of a strategy?

Logically, it does make sense to use a gemcitabine-based treatment with the nab-paclitaxel up front. The toxicities there that typically lead to patients coming off treatment are neuropathy and thrombocytopenia. You would then proceed to a second-line treatment, typically Onivyde and then 398. The regimen is combined with 5-FU. There is no bolus 5-FU. There’s leucovorin also given, and the side effects do not include neuropathy or thrombocytopenia. You do experience what we’ve all are used to, managing diarrhea and neutropenia. So patients can go on to a different toxicity profile, rest the bone marrow to some extent, rest the platelets, and then come on to a third-line therapy.

Alternatively, if you use a 5-FU—based treatment, that’s going to be FOLFIRINOX. Neuropathy is encountered with oxaliplatin that is not necessarily reversible. FOLFIRINOX has irinotecan in the regimen. It doesn’t make a lot of sense then to go on to Onivyde. It does not make sense to go on an MM-398, so you really are going to go to a gemcitabine-based treatment, typically gemcitabine/abraxane which may be challenging for patients in the second-line, especially if they’ve encountered neuropathy with FOLFIRINOX in the frontline. That’s why the first sequence, gemcitabine/nab-paclitaxel, followed by Onivyde and then 398 really does make sense.

It’s important to recognize that Onivyde is to be combined with 5-FU, leucovorin. It is not a monotherapy. There was an arm in that NAPOLI trial that used Onivyde as monotherapy, but that unfortunately was no better than the control arm.

Metastatic Pancreatic Cancer: Case 2

Henry R was diagnosed with adenocarcinoma in the body of the pancreas when he was 64 years old, following rapid weight loss, abdominal pains, and the development of venous thrombosis.

  • At diagnosis, measurable distant lymph node, liver, and lung metastases were observed
  • His CA19-9 level was 2760 U/ml and his concentration of albumin was 28 g/L. His ECOG performance status was 1.

Upfront treatment was administered with nab-paclitaxel and gemcitabine, which lasted for 4months:

  • At the time of progression, pain levels had increased interfering with daily activity and raising the ECOG performance status to a 2.
  • At this point, second-line therapy was initiated with liposomal irinotecan, fluorouracil, and folinic acid.
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