Expert Calls for More Research in Checkpoint Blockade for Upper Tract Urothelial Cancers (Lynch Syndrome)

Expert Calls for More Research in Checkpoint Blockade for Upper Tract Urothelial Cancers

 The excitement among urologic oncologists about the potential for checkpoint blockade treatments, especially in bladder cancer, is almost palpable. Results from ongoing trials involving atezolizumab, pembrolizumab, nivolumab, and avelumab in bladder cancer are eagerly awaited. But there is one subset of patients who require special attention: patients with upper tract urothelial cancer (UTUC). The “upper tract” sessions created quite a buzz among the attendees of the Society of Urologic Oncology annual meeting in Washington, DC, December 2-4.

“For my presentation, I was charged with talking about checkpoint blockade in UTUC, a topic for which there are no data,”........In addition, preclinical work has been conducted in the pan epithelial space, but it is not specific to upper tract.

Plimack offered some initial steps to further elucidate UTUC. “The first step is to look at the subsets in these larger trials and to see if there’s anything that stands out in the group. It may be that they perform just as well in these metastatic trials. I think therapy directed toward upper tract will come after it is better defined in the wider group.”

Mutations and mutational burden may play a role in treatment for both chemotherapy and immunotherapy. In some upper tract tumors, especially those associated with Lynch syndrome or certain carcinogens, there may be a hypermutation phenotype that may render those tumors more susceptible to immunotherapy.

This may be significant because mismatch-repair status has been suggested as a potential predictor of clinical benefit with pembrolizumab in a phase II study by Le, et al. 6.....

.....Although some of the findings reported with checkpoint inhibitors have been dramatic, Plimack emphasized that there are adverse effects. “It’s important not to under-emphasize them,” she said. “Defining treatment related toxicity for some of these immunotherapy trials has been a challenge.”