Muscle-Invasive Bladder Cancer: Role of Minimal Residual Disease in Adjuvant Therapy

Transcript:

Shilpa Gupta, MD: We learned a lot from IMvigor010, which was a negative trial for the primary end point, but it did teach us a lot about MRD [minimal residual disease] in this space. I’d love to hear from Andrea. What are your takeaways from the role of MRD and ctDNA [circulating tumor DNA] in this setting? What’s on the horizon?

Andrea B. Apolo, MD: Thanks for asking. We’re working in exciting times, with some biomarkers that may be able to select the patients who respond better or benefit the most. The problem with adjuvant therapy is that we overtreat patients. It’s hard to see the benefit of the therapy because a lot of patients may be cured. That’s true of all forms of disease. It’s hard to select patients who need the therapy. That’s why ctDNA is very exciting.

In the IMvigor010 study, there was an exploratory analysis looking at ctDNA-positive patients. It looked as if those patients did better when they received atezolizumab [Tecentriq] vs observation if they were ctDNA-positive. Based on that exploratory analysis, the IMvigor011 study was developed, where patients’ ctDNA is assessed. If they’re positive, then they go on to receive atezolizumab. It’s treats patients who are positive for ctDNA in the adjuvant setting—patients that might benefit. Therefore, we can see the benefit of the treatment, and we’re not overtreating patients.

Another trial is being developed through the Alliance for Clinical Trials in Oncology, in which patients are also treated based on their ctDNA. If they’re ctDNA positive, then they’re randomized to receive nivolumab [Opdivo] vs a more intense therapy, nivolumab plus another therapy. If they’re ctDNA-negative, then they’re randomized into immediate nivolumab vs nivolumab, when the ctDNA turns positive. It’s a very adaptive approach using a biomarker in a prospective manner. We’ll learn a lot from these studies.

Shilpa Gupta, MD: Mamta, in your practice, are you using the FDA-approved ctDNA test to guide your decisions?

Mamta Parikh, MD, MS: I haven’t started using it in clinical practice. Some trials are evaluating this. It’s a very fascinating area. The IMvigor data are interesting, but I’m not ready to allow them to guide my clinical practice. We need more trials, and the Alliance trial is very exciting and will help us further determine how to incorporate MRD into our practice.

Shilpa Gupta, MD: As Andrea said, it’s important to select patients. There’s unnecessary toxicity when we don’t know if overall survival is being affected by immunotherapy.

Transcript edited for clarity.