Significance of second progression-free survival in patients with advanced urothelial cancer who received platinum-based combination chemotherapy followed by pembrolizumab.

OBJECTIVES: The present study comprehensively investigated the significance of several factors reflecting the therapeutic effects of anticancer treatment on overall survival (OS) in advanced urothelial cancer (UC) patients receiving sequential systemic therapy. METHODS: This study included 101 consecutive advanced UC patients who received first-line platinum-based combination chemotherapy followed by second-line pembrolizumab. The impacts of the following factors on OS in these patients were analyzed: responses to chemotherapy, responses to pembrolizumab, progression-free survival (PFS) with chemotherapy, PFS with pembrolizumab, and second PFS (PFS2). RESULTS: The median age of patients was 71 years, and 35 and 66 had UC in the upper urinary tract and bladder, respectively. objective response rate to first-line chemotherapy and second-line pembrolizumab were 37.6% and 19.8%, respectively. Median PFS with chemotherapy, pembrolizumab, and PFS2 were 5, 4, and 9 months, respectively. Uni- and multivariate analyses of the five factors examined identified PFS with pembrolizumab and PFS2 as independent surrogates for OS, with PFS2 (hazard ratio [HR] = 0.23) being more closely associated with OS than PFS with pembrolizumab (HR = 0.31). Furthermore, uni- and multivariate analyses of various prognostic parameters showed the independent impacts of baseline performance status (PS) and neutrophil-to-lymphocyte ratio (NLR) on PFS2. CONCLUSIONS: The present results suggest the potential of PFS2 as an optimal surrogate for OS in advanced UC patients receiving standard sequential systemic therapy and indicate that intensive treatment needs to be considered for those with poor PS and/or high NLR prior to the introduction of first-line chemotherapy.

Renal allograft rejection after treatment with nivolumab in patients with metastatic renal cell carcinoma.

In recent years, immune checkpoint inhibitors (ICIs), such as nivolumab, pembrolizumab and ipilimumab, have been introduced into routine clinical practice for treating patients with several types of advanced cancer, including renal cell carcinoma (RCC). However, activation of the immune system against cancer cells by the use of ICIs could result in the induction of allograft rejection in organ transplant patients, and to date, the safety of treatment for organ transplant patients with ICIs has not been well-investigated. Here, we report a case of renal allograft rejection in a kidney transplant recipient with metastatic RCC (mRCC) after the administration of nivolumab. Four weeks after initiating treatment with nivolumab, the renal function, in this case, was markedly impaired, and pathological findings of renal biopsy specimens showed acute rejection characterized by marked infiltration of inflammatory cells. Steroid pulse therapy was performed in this case, and despite the lack of improvement in the renal function, his graft was salvaged. Collectively, these findings suggest that it is necessary to pay special attention to the potential for allograft rejection when introducing ICIs for solid organ transplant recipients.