Therapy for Locally Advanced Pancreatic Cancer

Transcript:Philip A. Philip, MD: The treatment of localized disease, that’s what we’re referring to in the adjuvant setting: patients who have resectable disease or, nowadays increasingly, patients who have maybe borderline resectable disease who undergo a few cycles of chemotherapy up front and they get surgery. Those patients we also treat within the adjuvant setting.

The key thing to remember is that the outcome of surgery, because it’s been so bad in this disease when we are only able to cure one of five patients who go through surgery, there is a lot of need to develop other treatments, like adjuvant therapy. We have reached a point where the adjuvant treatment at this time is going to be 4, and preferably 6, months of chemotherapy. And the drug we use is either gemcitabine or fluoropyrimidine. It could be 5-FU/leucovorin or even capecitabine. However, the benefit from using the 6 months of chemotherapy is still very modest. In fact, there’s a very modest improvement in the disease-free survival, which is the time until we discover the patient has a recurrence of the disease. And also, there has been a very modest benefit in terms of overall survival.

We still are losing most of our patients, and the median survival time is somewhere between 20 months and 24 months. So, really, it’s a short one, if we think of other cancers that we treat, especially cancers where surgery and adjuvant treatment has made a big impact on the outcome of the disease. That’s where we stand now in terms of adjuvant therapy of pancreatic cancer.

There are a number of studies that are currently ongoing. In fact, there is a study that completed accrual. And in this meeting in Chicago, they were going to present the results of the adjuvant gemcitabine versus gemcitabine plus capecitabine treatment; 6 months of treatment. I can tell you that it does appear that the combination helps the patients more than the gemcitabine. We have to see the details of the study because just having numbers is not enough. We have to understand the correct situation to be able to say whether we would recommend this for the next patient you see in a few days’ time.

The other trial is the APAC trial, which is sponsored by Celgene. And it’s a trial of gemcitabine plus nab-paclitaxel versus gemcitabine alone, 6 months, and no radiotherapy. There’s another trial running in Europe, which is a FOLFIRINOX regimen versus gemcitabine, and, again, 6 months of treatment. And there is an ongoing RTOG trial which uses straight chemotherapy with gemcitabine, but then randomizes patients into chemoradiotherapy versus no chemoradiotherapy. That’s a very important trial. Because, in this country, we still believe that radiotherapy is probably helpful, at least in some patients. Whereas in many parts of the world, including Europe, they don’t believe in the use of radiotherapy. I personally think that within the next 3 or 4 years, we’ll be coming back here to the studio with much better information and will be more definite on how to really recommend our adjuvant treatment.

Until that time, at the minimum, gemcitabine for 4 to 6 months, with or without chemo-radiotherapy at the end of the treatment, is really what we recommend for the patient. At least that is what I do in my practice. I don’t sandwich the radiation between initial chemotherapy and later chemotherapy. I give my patients chemotherapy. I give my patients the full dose of the chemotherapy or the full length of the chemotherapy to be more accurate, and then I restage them. And for patients who have no evidence of disease recurrence, those are the patients I would proceed with radiotherapy if I do that. I know most of the oncologists in this country are used to this sandwiching, but if we use it the way which makes more sense, which is to give the chemotherapy first and then the chemoradiotherapy, that’s probably better for the patient. And, in fact, the RTOG trial I mentioned uses that strategy.

Tanios Bekaii-Saab, MD: When we want to think about adjuvant chemotherapy, the question is whether adjuvant chemotherapy should come after surgery or what we call neoadjuvant, meaning before surgery. The rationale for moving chemotherapy, or therapy overall, prior to surgical resection is that more patients are likely to get treatment before surgery than after surgery. After surgery, there’s 10%, 20% of the patients that will have a hard time essentially recovering and therefore getting to treatment. So, that’s one. The second rationale to bring treatment before surgery is that some patients are metastatic already from the get-go, although it’s a micrometastatic disease, and giving them treatment before surgery may uncover that metastatic disease and would spare them the havoc of a large surgery.

So, the idea of bringing chemotherapy prior to surgery seems to work well in a number of different cancers. And in pancreas cancer, there have been small studies here and there that looked at that question. They mostly showed not much of a difference between neoadjuvant and adjuvant approaches. This has not been done on a large prospective trial. Right now, there is one study that’s looking essentially at a neoadjuvant approach with gemcitabine/nab-paclitaxel versus FOLFIRINOX. It’s a study sponsored by SWOG to look whether there is any benefit of using a doublet versus triplet prior to surgical resection.

In terms of the role of radiation prior to surgical resection, there hasn’t been a lot of work done. We know that in the borderline resectable, and the locally advanced pancreas cancers, with introducing the concept of radiation, specifically SBRT (stereotactic body radiation therapy). So, a short-course, hyperfractionated high dose of radiation may actually improve the resection rate and the clarity of the margins. But, more studies are needed. And some of that work is being done mostly in the borderline resectable and locally advanced disease, rather than the clearly resectable disease.

Transcript Edited for Clarity