Medicine Matters oncology

We presented the trial data for the RAPPORT clinical trial, which is a dual institutional Phase I/ Phase II clinical trial that was focusing on patients with limited spread of metastatic disease, oligometastatic disease with one to five sites from clear cell & renal cell carcinoma. In this study, patients were enrolled and received stereotactic radiotherapy to each site of disease, followed by eight cycles, or a short adjuvant course of pembrolizumab, a total of six months. The patients had a reasonable burden of disease, with our average having three sites.

There were 30 patients in total who were enrolled, and the median follow up was relatively long, at 2.3 years. Nine of the patients, or 30%, had a prior mastectomy, so there were patients who had previous treatments, and about a third of the patients also had prior systemic therapies. They were allowed to have one to two lines of systemic therapy prior to enrollment. From a safety perspective, this combination was very well tolerated, with only 13% or four patients having grade three toxicities, and none of the patients having grade four or grade five toxicities. And 80% of the patients were able to continue and complete all eight cycles of pembrolizumab.

From an efficacy perspective, the objective response rates, those patients achieving a complete response or partial response, was 63%. In comparison, the KEYNOTE-427 study, which was a first line pembrolizumab study in clear cell renal cell carcinoma, had an objective response rate of 34%. The medium progression free survival in our cohort was 15.6 months, as compared to 7.1 months in the KEYNOTE-427 study. There were almost half of the patients who were disease free and alive at two years at 45%. And the combination was also very locally effective, with the treated lesions having a local progression free survival of 92% for all of the 83 lesions that we irradiated.

So in summary, this combination seems to demonstrate both safety and seems to demonstrate some quite encouraging activity. And moving forward from here, it would be interesting to test this combination in the larger cohort of patients in a randomized fashion. This type of approach, while it is quite novel in oligometastatic patients because even though the approach in metastatic targeted therapy is actually recommended in guidelines for patients with oligometastic renal cell carcinoma. There is no prospective of clinical trial data available until the findings of this particular study. We think the combination of both radiotherapy and a shorter course of systemic immunotherapy may be promising in the future.