Harry H. Yoon, MD
Following the FDA approval of the PD-1 inhibitor pembrolizumab (Keytruda) in September, the field of gastric cancer and gastroesophageal junction (GEJ) adenocarcinoma is buzzing when it comes to immunotherapies.
on Gastrointestinal Cancers, Yoon proposed the use of PD-1 inhibitors in earlier lines of therapy. In an interview at the meeting, Yoon discussed the promise of immunotherapy and emphasized the importance of mismatch repair (MMR) deficiency testing.
OncLive: Please provide an overview of your discussion on gastric cancer.
I spoke about the most updated information that affects our standard practice, and what the most promising developments are on the horizon for gastric cancer.
Pembrolizumab was approved for all tumors that are MMR deficient. It seems that about 9% of gastric cancers are MMR deficient, and about 4% of GEJ adenocarcinomas are. I tend to perform MMR testing in all of my patients with gastric cancer and GEJ adenocarcinoma patients.
What is the future treatment for patients with this disease? Is it strictly immunotherapy?
There are other pathways that are promising, such as angiogenesis. Ramucirumab (Cyramza) was recently identified in a global frontline study to [have a] benefit with progression-free survival; it was combined with cisplatin and fluoropyrimidine. We don't know the full results or the magnitude of benefit, but that is an interesting pathway.
Going along with angiogenesis, the VEGFR tyrosine kinase inhibitors are really interesting. There are good preliminary data and those are now being evaluated in phase III studies. The other one is anti-Claudin (CLDN) 18.2, which is a gastric-specific cell-surface marker. There are interesting randomized phase II data showing that it may have promise. There are other areas, but immunotherapy is an area of very high interest.
What is one of the biggest unmet needs in this landscape?
There are so many. Patients tend to do rather poorly no matter what type of therapy that we give—even in the so-called "curative-intent" setting. The unmet need is basically anyone with disease that is something more than purely local disease—which is the vast majority of patients—maybe 85% to 90%. All that need is unmet.
What is the take-home message from your presentation?
The big thing is to understand and appreciate the role of MMR testing and to consider that in at least the second- or third-line setting, and maybe even earlier than that. Even if a patient has MMR proficiency, consider a PD-1 inhibitor in earlier lines of therapy—in something like a patient-assistance program. What I am talking about now is relevant to a US-based practice, where something like that may be available.
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