Practical Perspectives on Treatment of Advanced Gastric/GEJ Cancers - Episode 19

Advanced Gastric/GEJ Cancer: Sequencing Treatment


Manish Shah, MD: In terms of thinking about chemotherapy for gastric and GE junction cancer, we now have multiple options through multiple lines of therapy. That’s a great thing, and similar to how we think about it in colon cancer, we want to strategize and begin sequencing treatment and planning ahead. So, if a patient is PD-L1-positive, then I know pembrolizumab is an option in the third-line setting. I typically would use a platinum and fluoropyrimidine in the first-line setting, paclitaxel and Cyramza (ramucirumab) in the second-line setting, and pembrolizumab in the third-line setting. That leaves out irinotecan, and that’s OK for most patients. But if a patient is really quite robust and quite motivated, there may be an option to use a 3-drug regimen in the first-line setting and then irinotecan in the second-line setting and pembrolizumab in the third-line setting. I think these are things we have to think about and discuss with patients.

The goals of care through the lines of therapy, second and third line, remain the same. How do we maximize patients’ quality of life, maximize their disease control duration, and minimize side effects of treatment? We’re trying to use more and more targeted agents and less and less chemotherapy to reduce side effects. Neuropathy can be a problem, especially after you receive oxaliplatin or Taxol (paclitaxel) for a while, so we have to think about that as well. With these options, we have an opportunity to discuss with patients our goals of care that help us to manage and sequence.

Immuno-oncology has changed the face of solid tumor oncology. Recently, the FDA approved pembrolizumab for any tumor that was mismatch repair deficient. These tumors have a high neoadjuvant burden, and there are really quite compelling data that pembrolizumab in that setting can induce a response in 30% to 40% of patients and that the response can be durable. I’m talking years. That’s really practice changing. But outside that, pembrolizumab really has modest activity. It’s 10% to 15%, at least in the third-line setting. In the second-line setting, the study comparing it with chemotherapy was negative, in fact. Patients commonly ask, “Can I get pembrolizumab in the first-line setting and second-line setting?” We review the data and explain to them that their chances to control the disease and have a better quality of life are better with chemotherapy, at least at this time.

Transcript Edited for Clarity