Comparison of Oncological Outcomes of Pembrolizumab as Second-line Therapy and Maintenance Avelumab Therapy in Advanced Urothelial Carcinoma After Platinum-based Chemotherapy.

BACKGROUND/AIM: Sequential therapy using chemotherapy and subsequent immune checkpoint inhibitor (ICI) treatment prolongs the survival of patients with advanced urothelial carcinoma (UC). However, no comparison data for oncological outcome between pembrolizumab and avelumab has been reported. Thus, we compared oncological outcomes between pembrolizumab as second-line therapy and maintenance avelumab therapy in patients with advanced UC. PATIENTS AND METHODS: We retrospectively evaluated patients with advanced UC treated with pembrolizumab or avelumab between January 2018 and February 2023. We compared oncological outcomes after adjusting for patient characteristics. Immune-related adverse events (AEs) in each group were evaluated using the Common Terminology Criteria for Adverse Events. RESULTS: There were 186 and 44 patients in the pembrolizumab- and avelumab-treated cohorts, respectively. After propensity score matching, 43 patients from each group were selected and analyzed. Median progression-free survival from the initiation of pembrolizumab and avelumab treatments was 126 and 139 days, respectively (log-rank test, p=0.625). Median overall survival in the pembrolizumab and avelumab cohorts were 658 days and not reached, respectively (log-rank test, p=0.249). Thirty-eight (20.4%) and 14 (31.8%) all-grade immune-related AEs were observed in 186 pembrolizumab- and 44 avelumab-treated patients, respectively (chi-squared test, p=0.112). Regarding endocrine-related AEs, 12 (6.5%) and none (0%) were observed in pembrolizumab- and avelumab-treated patients, respectively (Fisher's exact probability test, p=0.129). CONCLUSION: Pembrolizumab and maintenance avelumab therapy provide equivalent oncological outcomes in patients with advanced UC. Although no significant difference was observed, there might be a potential risk of higher endocrine-related AEs due to pembrolizumab compared to avelumab maintenance therapy.

[Urological Comorbidities in an HIV-Infected Patient: A Case Report].

We report a case of a patient who developed several urological comorbidities associated with HIV infection. A 53-year-old male was diagnosed with HIV infection and AIDS. After 13 years, microhematuria was found and computed tomography (CT) revealed urolithiasis and a left renal tumor suspected of being renal cell carcinoma. Initially, he underwent transurethral lithotripsy. Stone analysis indicated that the stone was made of atazanavir. Then he received laparoscopic left partial nephrectomy. The pathological diagnosis was papillary type 2 renal cell carcinoma. Three years later, follow-up CT revealed a right renal pelvic tumor. Since right ureteroscopy showed that the tumor was papillary we diagnosed it as renal pelvic cancer and decided to perform laparoscopic right radical nephroureterectomy. His renal pelvic tumor was determined to be urothelial carcinoma by the pathological diagnosis. Intravesical recurrence occurred twice after the nephroureterectomy. His renal function gradually deteriorated during follow-up and we suspected that HIV nephrosis was one of the reasons for the deterioration. Hemodialysis was initiated at the age of 71.

Non-bacterial cystitis with increased expression of programmed death-ligand 1 in the urothelium: An unusual immune-related adverse event during treatment with pembrolizumab for lung adenocarcinoma.

INTRODUCTION: Immune checkpoint inhibitors are now a standard therapeutic option for lung adenocarcinoma. However, Immune checkpoint inhibitors often induce various immune-related adverse events. CASE PRESENTATION: The patient was a 78-year-old woman with lung adenocarcinoma who had a partial response to pembrolizumab. During treatment, she complained of pollakiuria and nocturia with painful micturition. Histological analysis revealed infiltration of CD8-positive and/or TIA-1 cytotoxic granule-associated RNA binding protein-positive lymphocytes and programmed death-ligand 1 expression in the urothelium. A diagnosis of immune-related adverse event cystitis was made based on these clinical and pathological findings. The patient's subjective symptoms and findings on cystoscopy improved dramatically after treatment with prednisolone. CONCLUSION: Immune checkpoint inhibitors-induced cystitis is extremely rare. This report is the first to include an immunohistochemical analysis of the urothelial epithelium in immune-related adverse event cystitis and describes an instructive case.

[Durable Response after Discontinuation Due to Immune-Related Adverse Events in a Patient with Metastatic Clear Cell Renal Cell Carcinoma : A Case Report].

A 70-year-old female with metastatic clear cell renal cell carcinoma was treated with nivolumab. After three dosages, she developed interstitial lung disease which required steroid therapy and nivolumab was discontinued. Thereafter, the target lesion continued to shrinkand the best response was partial response 15 weeks after discontinuation of nivolumab, the reduction rate of which eventually reached 49.1%. Other immune-related adverse events (irAEs), nephrotic syndrome and acute kidney injury developed 34 weeks after discontinuation of nivolumab, leading to irreversible kidney injury that required chronic hemodialysis. Although the target lesion continued to shrink, a new lesion developed 48 weeks after discontinuation of nivolumab. Subsequently, targeted therapies were added, but she died of cancer 13 months after resuming medical treatment. In this case, although various irAEs developed, the effectiveness of nivolumab was sustained even after it was discontinued.