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Introduction Li–Fraumeni syndrome, an autosomal dominant cancer predisposition syndrome caused by a pathogenic variant of TP53, a tumor suppressor gene, leads to a high risk from early childhood of developing various types of cancers. Here, we report a case of advanced ureteral cancer in Li–Fraumeni syndrome. Case presentation A 73 years‐old female patient, who had been diagnosed genetically as Li–Fraumeni syndrome; suffered from chondrosarcoma in the left pelvic joint, bilateral breast cancer, endometrial cancer, gastric cancer, and colon cancer in her history. She was diagnosed as unresectable advanced urothelial cancer during continuous magnetic resonance imaging surveillance, underwent avelumab maintenance therapy after the combination of gemcitabine and cisplatin chemotherapy. The efficacies of gemcitabine and cisplatin chemotherapy and avelumab maintenance therapy were good. Conclusion We report an advanced urothelial cancer in a patient with Li–Fraumeni syndrome who demonstrated good efficacies to sequential medical therapy.

Abstract Immune checkpoint inhibitor (ICI) therapy is often associated with cutaneous immune‐related adverse events (irAEs). Drug eruptions stemming from concomitantly or consecutively administered medications are also frequent and tend to be severe. We herein present three cases of severe drug eruption in patients receiving antibiotics during ICI therapy in which hypotensive shock occurring during antibiotic administration was followed by generalized erythema and prolonged organ damage. Three patients received tazobactam/piperacillin (TAZ/PIPC) for an infection during ICI treatment. A high fever developed in all the patients after a switch was made to other antibiotics (Figures 2–4). Since no skin rash was observed at fever onset, a flare‐up of the infection was suspected, and TAZ/PIPC administration was resumed. Thereafter, the patients suddenly experienced hypotensive shock and respiratory failure requiring ICU management for generalized erythema and organ damage. Since anaphylaxis caused by TAZ/PIPC is rare, the patients’ clinical findings might be a manifestation of synergistic, complementary, immunomodulatory effects of ICI. In patients receiving ICI therapy, a fever occurring during antibiotic administration may indicate the onset of an immune hypersensitivity reaction to the drug. Resumption of antibiotic administration, especially TAZ/PIPC, during such a period may trigger an excessive inflammatory response, leading to an anaphylaxis‐like reaction and organ damage.

Introduction In Lynch syndrome, urothelial cancer is the third most common cancer, following colorectal and endometrial cancers. Little is known, however, about the efficacy of immune checkpoint inhibitors in the treatment of metastatic urothelial cancer in Lynch syndrome. Case presentation A 49‐year‐old patient with metastatic urothelial cancer underwent pembrolizumab therapy after platinum‐containing chemotherapy. The efficacy of the pembrolizumab therapy was good. Her lung and bone metastatic lesions disappeared in imaging studies and her back pain decreased dramatically. Pathogenic mutations of MSH2 and BRCA2 were found in the DNA extracted from her tumor, and subsequent genetic analysis confirmed the germline pathogenic variant of MSH2. As such, this case was genetically diagnosed as Lynch syndrome. Conclusion We report metastatic urothelial cancer in a patient with Lynch syndrome who demonstrated a radiological complete response to pembrolizumab therapy. Accurate genetic diagnosis can provide useful information to both the patient and their relatives.

Abstract Background The paradigm of medical treatment for metastatic urothelial carcinoma is dramatically changing through the introduction of pembrolizumab. Aim We investigated the treatment effectiveness, the safety profile, and the prognostic factors of pembrolizumab in Japanese real‐world clinical practice. Methods and results The medical records of 74 consecutive Japanese patients with metastatic urothelial cancer (UC), who started pembrolizumab as a second‐ or later‐line treatment at our institution between January 2018 and March 2020, were reviewed and statistically analyzed. The median follow‐up period after initiation of pembrolizumab was 8.5 (interquartile range: 3.5–15.7) months. The objective response rate was 30.2%, the median progression‐free survival period was 4.9 months, and the median overall survival (OS) period was 13.3 months. Evaluation revealed that 39 (52.9%) patients experienced adverse events (AEs), among whom eight patients (10.9%) had severe AEs (grade 3 or more), including grade 5 hemophagocytic syndrome. Multivariate analysis indicated that the presence of liver metastasis, worse performance status (≥2), elevated serum lactate dehydrogenase, and increased C‐reactive protein were predictive of shorter OS. Conclusion We studied the effectiveness and safety profile of pembrolizumab therapy in Japanese UC patients. We believe that the data presented here will be useful for clinical physicians.