Treatment Strategies for Patients Who Progress on Adjuvant Pembrolizumab

Following the advent of adjuvant pembrolizumab in high-risk renal cell carcinoma, experts consider treatment strategies for patients who progress on adjuvant pembrolizumab.


Robert J. Motzer, MD: Two last points. First, for Mehmet. This has opened a whole new line of therapy for patients who are treated with adjuvant pembrolizumab [for renal cell carcinoma] but relapse. What’s your way of thinking about this in terms of recommending other treatments?

Mehmet A. Bilen, MD: Thank you so much, Bob. This is going to affect how we treat our patients and also our clinical trial eligibility and design. The timing of progression and the cyto-progression are important. For example, if someone completed a year of pembrolizumab and has a disease recurrence after another couple of years, I may treat this patient as having no prior line of therapy, with either I/O [immuno-oncology]–I/O or I/O–VEGF. But if progression happens while the patient is on adjuvant pembrolizumab, unless this is an oligoprogression, sometimes we use local therapy, such as SBRT [stereotactic body radiotherapy] or resection. Then I like to bring VEGF on board, especially if this has multiple new spots, like liver metastases and bone metastases. This tells me that there’s some intrinsic I/O resistance, and I want to bring another class of agent on board, either a single-agent TKI [tyrosine kinase inhibitor] or I/O–TKI, which we discussed earlier. We have many of those combinations available, but hopefully, down the road, we’ll get biomarker-driven sequencing trials that will give us more data on what to do and how to do it.

Robert J. Motzer, MD: All right. The last question is for David. Obviously, we’re very much involved in neoadjuvant approaches for bladder cancer. For kidney cancer, is there a role for neoadjuvant therapy or any interest in pursuing it?

David H. Aggen, MD: It’s likely that we’re going to be looking at combination therapies in the neoadjuvant setting in the future. The PROSPER RCC trial, which has completed accrual, is looking at a neoadjuvant and adjuvant PD-1 approach. I’m a little concerned that we’re not going to see dramatic responses with PD-1 monotherapy. There was a phase 2 study out of MSK [Memorial Sloan Kettering Cancer Center in New York, New York]. Maria Carlo is the first author. In 15 patients, the largest reduction in primary tumor with PD-1 neoadjuvant therapy was about 40%. It’s not clear that immune priming in kidney cancer is going to be equivalent in the neoadjuvant setting as it is in other diseases. The future of a neoadjuvant approach is very much up in the air, and we may be treating patients with I/O–TKI up front and very carefully considering cytoreductive nephrectomy in many cases.

Transcript edited for clarity.

Related Videos
Experts on RCC
Experts on RCC
Data demonstrate the feasibility of automated glomerular filtration rate prediction to decide between partial nephrectomy and radical nephrectomy in kidney cancer, according to an expert from the Cleveland Clinic.
Experts on RCC
Experts on RCC
Early phase trials investigating cellular therapies, bispecific antibodies, and antibody-drug conjugates for refractory kidney cancer may uncover strategies to overcome resistance mechanisms.
Increasing cancer antigen presentation as well as working with tumor cells in and delivering novel cells to the microenvironment may help in overcoming mechanisms of immune checkpoint inhibitor resistance in refractory renal cell carcinoma.
Lenvatinib plus pembrolizumab appears to be the best option for patients with refractory metastatic renal cell carcinoma who are progressing on immunotherapy combinations or are lenvatinib naïve.
Ipilimumab monotherapy does not appear effective in driving complete responses in refractory renal cell carcinoma despite yielding some progression-free survival intervals, according to an expert from the University of Texas Southwestern Medical Center.
An expert from the University of Texas Southwestern Medical Center discusses several phase 3 clinical trials supporting the use of various single-agent and combination immunotherapy regimens for advanced kidney cancer.
Related Content