Sequencing Strategies: Metastatic Pancreatic Adenocarcinoma - Episode 2

Choosing Frontline Therapy in Metastatic Disease


John L. Marshall, MD: For metastatic pancreas cancer, we’ve gone from a gemcitabine-only world to 2 main recipes that we recommend to patients. One is gemcitabine and nab-paclitaxel (gemcitabine and Abraxane). The other is FOLFIRINOX—a 5-FU—based regimen with irinotecan and oxaliplatin. They both perform similarly. They have different toxicities, different administration, and different wear and tear on patients. And so, when picking between those, we are trying to assess what that patient’s needs are. How much intensity can they tolerate? “How much more bang for the buck do I get from a more intensive regimen?” And, “What will the other regimen do if I pick that?” What I would really like is some sort of biomarker that would tell me that 5-FU–based therapy or gemcitabine-based therapy is right. As we think about this and we talk among ourselves, it’s pretty clear that some patients respond to one and some other patients respond to the other. But, it’s kind of rare that we see patients respond to both. In many ways, we’re guessing, right?

In my world, most of the pancreas cancer patients are a little older. They can be more frail. And so, it is rare for me to give a patient FOLFIRINOX, for example. It’s really the exception, when I would pick that for metastatic disease. I know I have lines of therapy. Gemcitabine and nab-paclitaxel is a very easy way to start, for most patients. The benefit rates are essentially the same as those of FOLFIRINOX. My basic strategy is, why wouldn’t I give gemcitabine and nab-paclitaxel first? And so, most of our patients end up with that regimen.

Fadi Braiteh, MD: Few patients who present with pancreatic adenocarcinoma are going to be candidates for surgery, upfront. The second-largest proportion would be for those who are borderline resectable. Unfortunately, the majority remain to be those patients who have locally advanced disease or disease that has already spread beyond the pancreas. The treatment is of a palliative nature. Yes, it is still a terminal illness. This is a disease in which the patient will unfortunately die. The goal is to prolong and improve the quality of life. This is very important to discuss with the patient. It is also important to introduce symptom management and some other supportive care, early on. And, most importantly, to take these things into consideration when we choose what the best systemic chemotherapy modalities would be for these patients. This can vary anywhere from the poor-performing patients to those who continue to use single-agent gemcitabine. It’s been about 2 decades since it has been introduced on the market.

In the last 6, 7 years, we had different modalities added to frontline treatment. We have 2 regimens that have not been compared head-to-head—the albumin-bound paclitaxel plus gemcitabine, or FOLFIRINOX. There are different ways of providing it. Again, we need to take preexisting comorbidities of patients into consideration—neuropathy, diabetes, etc. What’s their bone marrow reserve? What has happened? Often, there have been patients who had their pancreatic cancer diagnosed at an earlier stage, who receive a combination of neoadjuvant chemotherapy, surgery, radiation, etc. They recur. So, the time lapse since that treatment was completed and the aggressiveness of the disease are very important factors to take into consideration when we choose treatment.

Sometimes, comorbidities can be improved with appropriate management. The performance status of the patient can dramatically improve from ECOG 2 to ECOG 1 or ECOG 0, with appropriate management.

Colleagues always reach out to me to ask me about a particular case. “What would be the best approach?” The best approach, for me, is to always enroll the patients, when eligible, in a clinical trial. I encourage all of my colleagues to look into enrolling patients in clinical trials. In clinical trials, we gain knowledge to bring new studies and new treatments, and we learn more about delivering better care to patients.

But, outside of clinical trials, think about these patients. Has he or she been exposed to any cytotoxic drug before, in the neoadjuvant or adjuvant setting? What has the time lapse been? If it’s de novo advanced pancreatic adenocarcinoma, think about the multiple steps. Is this patient going to make it to second- and third-line therapy? And, of course, performance status is a big differentiator.

Other prognostic factors that we often look at are albumin level, the neutrophil lymphocyte ratio, et cetera. These are secondary. Get the patient in good shape. The way you see them on day 1 may not be the way that they are when they come back a week or 2 later. Often, they improve with very appropriate symptom control—pain management, opioid-induced constipation, and malabsorption. Depression—remember that 50% of patients have signs or symptoms of depression that predate their diagnosis of pancreatic cancer. This is very important. Have the discussion with the patient about what they wish for, more than once. Breaking bad news of pancreatic adenocarcinoma can be overwhelming to the patient and their family members.

Transcript Edited for Clarity