Eileen M. O'Reilly, MD: Aligning Treatment With Updates in NCCN Guidelines

How would Henry's treatment course align with the recent updates to the NCCN guidelines?

This gentleman is very symptomatic at presentation with weight loss, decrease in appetite, and has a number of the classic features that are associated with this disease—so he’s symptomatic. He has venous thromboembolic complications, which occur in a proportion of people with pancreas cancer at presentation. He has a reasonable performance status but his albumin level is low and his disease burden sounds high. This is the type of person that you worry that they’re on that progressive downward trajectory and need to get started on treatment sooner rather than later to stabilize their disease and hopefully improve their symptoms and extend life.

This gentleman went on to receive standard of care with gemcitabine/nab-paclitaxel, had disease control for about 4 months which is plus or minus average in that range, and then went on to receive a second-line therapy. His performance status at the time of initiation of second-line therapy sounds like KPS of 70%, so again on the decline in terms of well-being.

Liposomal irinotecan, 5-FU, and leucovorin has been evaluated in comparison to 5-FU and leucovorin in comparison to irinotecan and was demonstrated to have a survival advantage. I think it’s important to acknowledge that liposomal irinotecan on its own was not superior to 5-FU and leucovorin and that’s not a recommended approach in this setting. For a patient that’s well enough, it is logical to consider the treatment strategy undertaken here of liposomal irinotecan following gemcitabine-based therapy. That’s the exact setting where this drug received its approval, and we’ll just expand on that a little bit and say that it was in a previously treated gemcitabine setting. That could be gemcitabine given, as it was here, in a frontline treatment for metastatic disease. It could be gemcitabine given in a neoadjuvant setting or even gemcitabine given in a postoperative adjuvant setting and then on development of metastatic disease, linking to this regimen.

With regard to the NCCN guidelines, these have evolved to reflect the fact that there are now more choices both up front with the 2 major regimens but also that other gemcitabine-based combinations may have utility. For example, for patients with a less favorable performance status as initial treatment, gemcitabine, capecitabine might be considered. For individuals with a genetic underpinning to their cancer, for example, aBRCAmutation, it’s an accepted consideration to use a platinum-based treatment.

In addition to FOLFIRINOX, cisplatin and gemcitabine, or even FOLFOX, might be an option for that individual. For patients who have a higher performance status score, initial therapy single-agent treatment with gemcitabine represents an appropriate choice in the frontline.

Respecting what was given frontline will influence what would be the consideration second-line, so 5-FU—based therapy frontline, gemcitabine second-line, gemcitabine/nab-paclitaxel frontline, liposomal/irinotecan/5-FU, logical second-line, and then oxaliplatin-based therapies if a third-line treatment is appropriate. All the time being mindful as we treat these patients of if there is a clinical trial consideration. Is that a suitable option? Is it a logistic option? Is it an option that the patient and family are interested in? Because that’s ultimately going to have the biggest impact in terms of additional choices for these patients as we move forward with treatment for this disease.

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.