How do you treat clear cell renal cell carcinoma with metastatic recurrence while on adjuvant pembrolizumab?

My colleagues and I recently tried to address this question in a review paper in the Kidney Cancer Journal which is worth a read.

In the absence of prospective data in this space, we provide recommendations for clinicians based on existing evidence and constructed a potential algorithm to consider.

For a patient who progresses while on adjuvant pembro, we generally recommend treatment with single-agent VEGFR TKI. For a patient with metastatic recurrence after completing adjuvant pembro, treatment recommendations differ based on the time from the last pembro dose until recurrence given the persistent receptor occupancy of ICI even months after discontinuation. If recurrence occurs within 6 months of the last dose, we recommend single-agent...

In general, I have given very little adjuvant pembro. There have been other adjuvant IO studies in RCC which have been negative for DFS. I am eagerly awaiting the OS signal before committing to the routine use of adjuvant pembro. With respect to this question, I think the kind of progression matters. For instance, if there is good disease control overall, but oligometastatic progression, I would favor SBRT to these lesions with the continuation of IO alone. If there is more widespread progression, then I would switch to a TKI alone approach. There is nice data for the use of IO/IO combinations in patients with sarcomatoid differentiation, but I would still switch to a TKI in these patients with disease progression on adjuvant pembro. Howeve...