Sequencing Strategies: Metastatic Pancreatic Adenocarcinoma - Episode 7

Second-Line Decision-Making in Pancreatic Cancer


Kenneth H. Yu, MD: When I consider second-line therapy for patients with advanced pancreatic cancer, a lot of it depends on what treatment they received in the frontline setting. Then, again, we must always consider the clinical situation. What’s the patient’s performance status? What are their medical problems, and how did they develop? What toxicities have they experienced in the frontline setting? In general, when patients start with gemcitabine-based chemotherapy in the frontline setting, if they remain relatively fit and have not developed a lot of medical problems—if we are considering combination chemotherapy—I will generally treat them with nanoliposomal irinotecan. The data are really the strongest for that approach in the second-line setting.

For patients who start out with the 5-FU—based chemotherapy approach, I’ll switch to gemcitabine-based chemotherapy. If they can tolerate combination chemotherapy, it’ll be gemcitabine plus nab-paclitaxel. So, that’s the general approach. There are always considerations that you have to have. If they’ve developed neuropathy in the frontline setting, I might be a little bit more reluctant to give a drug like nab-paclitaxel in the second-line setting. If they’ve developed a lot of diarrhea or gastrointestinal toxicities in the frontline setting, nanoliposomal irinotecan may not be the right approach either. But for most patients, this is a sequence that I follow. For patients who are really fit and motivated, even in the community setting, I would encourage doctors to enroll patients into a clinical trial or encourage patients to seek enrollment into a clinical trial. For patients who are relatively fit and are motivated, in the second-line setting, I would still encourage community oncologists to either enroll those patients into clinical trials or refer them to academic medical centers—where they can participate in a clinical trial.

John L. Marshall, MD: We see more and more patients whose pancreas cancer gets under control. We all were taught, and we all learned that pancreas cancer is kind of a crash-and-burn disease. You help them a little bit, but not for very long. But now with our new medicines, we’re actually stabilizing the cancer. There are more and more patients who are getting earlier diagnoses. There’s approved recognition out there for diagnosing this disease. So, you’re seeing more and more patients who’ve been through frontline therapy, who either benefited from that or stabilized on that, who eventually progress somewhere between 5 to 8 months later. They are still fine and want subsequent lines of therapy. In that group of patients this is a choice, to move on to second-line therapy.

There are some patients who do not respond to first-line therapy. Right from the get-go, they are refractory to whatever treatment you propose. In those patients, we sometimes catch them, right? Their performance status is falling. They’re not doing very well. We change therapy, and we catch some of those patients. And so, in my opinion, even in that patient population, if you’ve got the right pit crew behind them—good support and all of that—that’s a patient who should be exposed to second-line therapy, with the hope of getting that treatment to stabilize.

Transcript Edited for Clarity