David H. Ilson, MD, PhD: We need to consider what do we do with a patient who’s receiving upfront chemotherapy. With a regimen like capecitabine/oxaliplatin or FOLFOX [leucovorin, fluorouracil, oxaliplatin], which includes 5-FU [5-fluorouracil] and oxaliplatin, we’re limited with the continuation of the platinum agent because of the risk of sensory neuropathy. Typically, around the fourth or fifth month, if the patient is still responding to treatment or has stable disease, we would change that patient to maintenance 5-FU alone. Some would argue to switch them to capecitabine to avoid the infusional part of the treatment.

GI [gastrointestinal] oncologists have never favored observation of patients off treatment. We tend to continue treatment until disease progression. That upfront maintenance therapy would be to continue the fluorinated pyrimidine until progression, and then second-line options would come into play later. What about switch maintenance? It goes against oncologic principles. If a patient is stable or responding to a treatment, we’re not going to change that treatment. The standard of care would be to continue the maintenance therapy with infusional 5-FU or capecitabine.

The JAVELIN Gastric 100 trial was a randomized trial in which all patients got upfront fluorinated pyrimidine platinum chemotherapy, and if they were responding or had stable disease four months or so into treatment, they were then randomized to continue maintenance therapy with the fluorinated pyrimidine or switch to maintenance therapy with a biologic, avelumab. This trial was looking at superiority for the avelumab maintenance arm, and this was a negative trial. It did not show that avelumab was superior to chemotherapy. Obviously, patients would respond early on to their chemotherapy regimen, but patients do continue to show response to ongoing treatment. There was a trend toward higher response in the avelumab arm, but no significant differences in progression-free and overall survival.

As with all the immunotherapy trials, there’s a subset of patients who benefit. We often see a late benefit with immunotherapy trials, which makes the argument that we should continue to use these drugs in most patients later line and that these patients don’t benefit from earlier use of these drugs. The tail on the curve, the late benefit, really supports the current usage of these drugs, which is in PD-L1–positive patients who are chemotherapy refractory, where we will see a benefit. The exception would be the MSI [microsatellite instability]-high patients, but that was not the subject of the JAVELIN Gastric 100 study. It was really trying to identify superiority for switch maintenance with immunotherapy, and the trial failed to achieve that outcome. However, it did not show that immunotherapy was inferior: it just wasn’t better than chemotherapy. But the trial does not make the argument that earlier use of immunotherapy as a maintenance strategy should be standard.

Transcript edited for clarity.