A Phase II Clinical Trial of Pembrolizumab Efficacy and Safety in Advanced Renal Medullary Carcinoma

Simple Summary Renal medullary carcinoma (RMC) is an aggressive type of kidney cancer. Traditional treatments have limited effectiveness, so new strategies are needed. Studies of RMC tissues found signs of inflammation, suggesting that immune checkpoint therapies could be a potential treatment option. In this study, we tested the effectiveness of pembrolizumab, an immune checkpoint inhibitor in a group of patients with RMC. Unfortunately, the results showed that pembrolizumab did not stop tumor growth. All the patients experienced rapid disease progression. One patient had such rapid progression that they had to stop the treatment less than a week after receiving pembrolizumab. In conclusion, this study demonstrated that pembrolizumab did not show any clinical benefits in patients with RMC. Background. Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC. Methods. A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated for PD-L1 expression and for tumor-infiltrating lymphocyte (TIL) levels. Somatic mutations were assessed by targeted next-generation sequencing. Results. A total of five patients were treated. All patients had advanced disease, with the majority of patients (60%) having metastatic disease at diagnosis. All patients had rapid disease progression despite pembrolizumab treatment, with a median time to progression of 8.7 weeks. One patient (patient 5) experienced sudden clinical progression immediately after treatment initiation and was thus taken off trial less than one week after receiving pembrolizumab. Conclusions. This prospective evaluation showed no evidence of clinical activity for pembrolizumab in patients with RMC, irrespective of PD-L1 or TIL levels.

Automated summary

Renal medullary carcinoma (RMC) is a highly aggressive kidney cancer and traditional treatments are not effective. Inflammation was found in RMC tissues, suggesting that immune checkpoint therapies could be a potential treatment option. However, the study showed that pembrolizumab, an immune checkpoint inhibitor, did not have any clinical benefits in patients with RMC.