Immune Checkpoint Inhibitors as Switch or Continuous Maintenance Therapy in Solid Tumors: Rationale and Current State - Episode 4
Two oncologists highlight practical considerations when choosing maintenance therapy.
Jason R. Brown, MD: So, interesting questions that the paper raised. Especially toward the end of the paper, I feel like they brought up some good points especially in regards to writing clinical trials using those maintenance strategies and biomarkers for those maintenance strategies. Biomarkers are going to be especially important in determining what patients get the benefit. What we’ve seen is PD-L1 [programmed cell death ligand-1] has been reported especially in the avelumab study. And while there’s benefit in the PD-L1-positive patients, there’s also benefit in the entire population as a whole. That may not be the only biomarker that we end up needing to be considering. We might want to end up considering tumor mutational burden. Potentially genomic classifiers like TGF-beta [transforming growth factor-beta], that may be something that we want to look at down the road in terms of determining what subset of patients are really going to get the most benefit from this strategy.
Shilpa Gupta, MD: Yeah, and I think that also brings us to the point about using circulating tumor DNA to see which patients may benefit. And, as we learned from another adjuvant study of atezolizumab in bladder cancer, it was a negative study, but it did show benefit in identifying patients who might benefit from adjuvant treatment. I think moving forward certainly we could utilize that approach to select which patients are most likely to respond and spare others the treatments.
Jason R. Brown, MD: Yeah, cell-free DNA could be really beneficial for our patients and this brings the point to correlative studies that are important in trials. I think another important thing thinking about clinical trials is the use of endpoints. One of the endpoints that this paper brings up is PFS2 [second progression-free survival], progression after the next round of treatment. In your experience writing clinical trials, have you found PFS2 to be a particularly useful endpoint.
Shilpa Gupta, MD: Yeah, I’ll be honest with you, PFS2 is a relatively new endpoint. We’re seeing that reported in a lot of prostate trials. I don’t know what the main significance of this might be. At the end of the day, we do want to see survival benefit. Yeah, PFS on any one therapy is useful, but if it is not translating into overall survival benefit then it makes you wonder what is the advantage of using the treatment if we have further effective subsequent therapies available for patients.
Jason R. Brown, MD: I think I agree. Overall survival is going to be the gold standard for these trials. But I think it would be interesting to look into some of these other secondary endpoints and maybe not so much in bladder cancer but especially other cancers that may have long-term overall survival, seeing what could potentially be a useful surrogate.
Transcript edited for clarity.