Progression on Adjuvant Therapy

Source: OncLive, August 2019

Jeffrey S. Weber, MD, PhD: OK, so let me ask you this, if we can switch gears a very small amount. We all agree the adjuvant therapy has really changed how we treat our melanoma patients or the availability of adjuvant BRAF/MEK, dabrafenib-trametinib, nivolumab, pembrolizumab. What do you do when they fail? Because this was never an issue before. Now it’s an issue in clinical practice. What happens? Ryan, what happens when you see a patient who has had adjuvant nivolumab or pembrolizumab, and they progress? Does the rapidity of progression impact on what you recommend? And is there an obvious first recommendation for them?

Ryan J. Sullivan, MD: It’s the question that we’re having to answer more frequently now that we’re offering adjuvant immunotherapy in patients who are relapsing. There’s no great answer to it. I think the first thing we need to define is when patients relapsed, did they relapse because they developed resistance to the therapy? Or did they relapse sort of on a time line that they would have relapsed anyway? For example, if somebody is receiving nivolumab or pembrolizumab in the adjuvant setting and then relapses while on it, I’m not going to give them a single-agent PD-1 [programmed cell death protein 1] inhibitor in the metastatic setting or unresectable setting.

But if they relapsed several years later, I might consider offering single-agent therapy or a combination immunotherapy for that patient. I think the timing of relapse does matter. The earlier the relapse, the more likely that we’re dealing with a truly resistant situation and we need to escalate therapy.