Certainly, second-line therapy is becoming increasingly common because first-line therapies are better than they used to be. The combination regimens, such as FOLFIRINOX and gemcitabine + nab-paclitaxel, have led to increased response rates and increased survival. This means that patients are often healthier in the second-line setting. They have also had a good experience in the first-line setting because the drug reduced the cancer burden, potentially increased their quality of life, and certainly extended their life. Therefore, patients are more likely to participate in second-line treatments. Second-line treatment options have expanded based on the findings of the recent NAPOLI trial of nanoliposomal irinotecan with fluorouracil and folinic acid. As a result of this trial, the utilization of nanoliposomal irinotecan, in combination with fluorauracil and leucovorin, was approved by the FDA for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy and is currently recommended by the treatment guidelines. Second-line choices vary depending on what treatment was used in the first-line setting. For instance, if you used FOLFIRINOX in the first-line setting, you could use gemcitabine + nab-paclitaxel in the second-line setting. If you used gemcitabine + nab-paclitaxel in the first-line setting, you could use nanoliposomal irinotecan in the second-line setting. So, there are certainly more options for first- and second-line therapy, relative to what we previously had for pancreatic cancer. 

Second-line regimens are of increasing importance in pancreatic cancer because patients are doing better. When they are progressing from first-line therapy, they tend to be in better shape and are eligible for more treatment in the second-line, which can be highly effective. The fact that the FDA has approved a second-line regimen speaks to that point because the FDA tends to be sort of behind what clinical practice dictates. We have been seeing these patients for quite a long time, based on their outcomes from FOLFIRINOX and gemcitabine or nab-paclitaxel. It is not surprising to see the trends that more and more patients are receiving second-line therapy and that a second-line therapy, when it came under FDA scrutiny, was approved because it continued to extend survival. 

We have seen this in other gastrointestinal malignancies, such as colorectal cancer. If you get people into multiple lines of therapy, they tend to live longer. It is not just because they have lived long enough to have multiple lines of therapy. It is because each line of therapy has a survival benefit. It is important that people are kept in pretty good shape, and that we do not drag out our first-line therapy. If first-line therapy is working, that is great. If it stops working, we have a second-line option ready. We can try third-line clinical trials or chemotherapy that people have not had yet. If we see somebody with a decent performance status starting out, our goal is to try to help them maintain that and quality-of-life, obviously. As you get into later lines of therapy, it becomes increasingly important for people, but part of maintaining that quality-of-life and performance status is the efficacy of drugs taken to slow the decline in performance status; patients will generally live longer and tolerate the therapy longer as well.