Explore the vast range of titles available.

Background/Aim: This study retrospectively investigated the impact of enfortumab vedotin (EV) monotherapy on the oncological outcome, safety profile, and health-related quality of life (HRQoL) in patients with metastatic urothelial carcinoma. Patients and Methods: We assessed 26 consecutive patients who had received EV monotherapy after failure of platinum-based chemotherapy and immune checkpoint blockade therapy at our single institution from December 2021 to January 2023. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and EORTC QLQ-C30 as an HRQoL instrument were evaluated. Results: The ORR and DCR were 57.7% and 80.8%, respectively. EV was effective regardless of the patient and tumor characteristics, including the efficacy of previous systemic therapy, performance status, number of Bellmunt risk factors, and presence of variant histology. With a median follow-up time of 7.5 months, the median durations of PFS and OS were 5.4 months and 10.3 months, respectively. Grade ≥3 AEs included neutropenia (15.4%), fatigue (7.7%), appetite loss (7.7%), rash (3.8%), febrile neutropenia (3.8%), hyperglycemia (3.8%), and interstitial pneumonia (3.8%). AEs resulting in withdrawal of EV, interruption of EV, and dose reduction occurred in two (7.7%), nine (34.6%), and 13 patients (50.0%), respectively. The EORTC QLQ-C30 scores from baseline to post-EV introduction remained stable. Conclusion: EV monotherapy demonstrated promising anti-tumor activity and tolerability in patients with metastatic urothelial carcinoma.

This study aimed to clarify the impact of proton pump inhibitors (PPIs) on oncological outcomes in patients who received pembrolizumab for advanced urothelial carcinoma (UC). Forty advanced UC patients treated with pembrolizumab were retrospectively reviewed and divided into two groups (PPI: 15 patients; without PPI: 25 patients). Tumor response and survival were compared between these groups. The factors associated with survival were also investigated. The objective response rate was significantly lower in the group with PPIs compared with the group without PPIs. Both progression-free survival (PFS) and overall survival (OS) were significantly shorter in the group with PPIs than in the group without PPIs. The use of PPIs was a significant predictor of poor PFS and OS in multivariate analysis. The use of PPIs was negatively associated with tumor response and survival in patients with advanced UC treated with pembrolizumab.

This study retrospectively investigated the impact of squamous differentiation on the prognosis of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Among the 244 consecutive patients who underwent RNU at our Institution from May 2005 to October 2019, 224 were analysed. Metastasis-free (MFS) and overall (OS) survival rates were evaluated using Kaplan-Meier analysis and Cox regression analysis. With a median follow-up time of 58 months, the groups with pure UTUC (n=197) and UTUC with squamous differentiation (n=27) had 5-year MFS rates of 65.2% and 40.9% (p=0.005) and 5-year OS rates of 74.4% and 49.0% (p=0.002), respectively. Multivariate analyses revealed that the presence of squamous differentiation was significantly associated with poor MFS (hazard ratio=1.88; p=0.027) and OS (hazard ratio=1.70; p=0.048). Squamous differentiation in UTUC appears to be an independent predictor of poor prognosis after RNU for UTUC.

Remarkable developments in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been achieved over the past decade. Although targeting the novel androgen receptor axis and using chemotherapeutic agents have improved survival, mCRPC is still a lethal disease. A better molecular characterization of cancer resulted in the determination of the important role of homologous recombination repair (HRR) genes in cancer development, and poly (ADP-ribose) polymerase (PARP) is one of the most attractive therapeutic targets. Recent clinical studies have demonstrated that PARP inhibitors significantly improve oncological outcomes in patients with mCRPC harboring BRCA mutations, and PARP inhibitors are becoming a standard of care for these patients. However, not only PARP inhibitors, but also chemotherapeutic agents such as platinum agents, taxanes, and radium-223 are active in HRR gene mutation carriers, and platinum sensitivity may predict the efficacy of PARP inhibitors for mCRPC. The combination of PARP inhibitors with other anti-cancer agents may overcome resistance mechanisms against PARP inhibitors and lead to survival benefits. Appropriate treatment sequences and combinations may change the therapeutic landscape of DNA repair deficient mCRPC.

IntroductionSmall cell carcinoma (SCC) of the kidney is extremely rare. Although the majority of patients with advanced renal small cell carcinoma were treated with a combination of cisplatin and etoposide, the efficacy was limited. We report the first case with renal small cell carcinoma who received nivolumab and cabozantinib.Case presentationA 57-year-old woman was referred to our hospital with a massive left kidney mass and several bone, lymph nodes, liver, and lung metastases. A left renal mass biopsy made the diagnosis of small cell carcinoma. Nivolumab and cabozantinib were used in combination therapy. The tumors were stable during the treatment for 4 weeks. However, the treatment was halted due to a serious adverse event, immune-related hemophagocytic lymphohistiocytosis. Although immune-related hemophagocytic lymphohistiocytosis was resolved with corticosteroids, the patient died 3 months after the initiation of nivolumab and cabozantinib.ConclusionWe reported the first case of renal small cell carcinoma treated with nivolumab and cabozantinib.

To clarify the clinical significance of the temporary elevated C-reactive protein (CRP) levels followed by a decrease below baseline (CRP flare response) after administration of pembrolizumab to patients with advanced urothelial carcinoma (UC). We retrospectively reviewed 31 patients with advanced UC who received pembrolizumab. Patients were categorized into 3 groups (flare-responder, responder, non-responder) according to early CRP kinetics. Intergroup tumor response and survivals were compared. Objective response rates of flare-responder, responder, and non-responder groups were 75%, 80%, and 26%, respectively. Median overall survival was not reached in flare-responder and responder groups, and was 10.2 months in the non-responder group (p=0.03). Furthermore, the flare-responder group did not reach median progression-free survival, and for the responder and non-responder groups it was 15.2 and 2.8 months, respectively (p=0.03). CRP flare response might be a promising biomarker in patients with advanced UC who received pembrolizumab.

We aimed to clarify the association between body mass index (BMI) and clinical outcomes of pembrolizumab treatment for advanced urothelial cancer (UC). We retrospectively reviewed the records of patients with advanced UC who received pembrolizumab after chemotherapy between March 2018 and December 2021. Patients were divided according to BMI into the non-overweight group (BMI <25 kg/m ) and the overweight group (BMI ≥25 kg/m ). We compared the two groups' tumour response, survival rates, and incidence of immune-related adverse events (irAEs) and investigated the factors predicting survival. Of 84 eligible patients, 63 (75%) and 21 (25%) were in the non-overweight and overweight groups, respectively. Although the objective response rate was higher in the overweight group (55%) than that in the non-overweight group (29%), the difference was not significant. Progression-free survival (PFS) was significantly longer in the overweight group (median 15.2 months) than that in the non-overweight group (median 4.8 months; p=0.01). Overall survival was also longer in the overweight group (median 36.1 months) compared to that in the non-overweight group (13.4 months), but the difference was not significant (p=0.11). Multivariable analysis showed that overweight was significantly associated with favourable PFS. Any and severe (grade 3) irAEs were observed in 15 (24%) and 5 (7.9%) patients in the non-overweight group, respectively, and in 8 (38%) and 2 (9.5%) patients in the overweight group, respectively, but the differences were not significant. BMI was associated with oncological outcomes in patients with advanced UC who received pembrolizumab but not with the development of irAEs.

Data on the C-reactive protein (CRP) flare response in patients with metastatic and unresectable urothelial carcinoma (mUC) are limited. The present study aimed to clarify the clinical significance of the CRP flare response in patients with mUC who received pembrolizumab. Between March 2018 and December 2022, patients with mUC who received pembrolizumab following chemotherapy were retrospectively reviewed. Patients were categorized into three groups based on the early kinetics of CRP: i) Flare-responders, in which CRP levels increased >2-fold from baseline (BL) within 1 month after pembrolizumab administration (CRP flare) and decreased to below-BL levels within 3 months; ii) responders, in which CRP levels decreased ≥30% from baseline within 3 months without CRP flare; and iii) non-responders, which included the remaining patients. Tumor response, survival and incidence of immune-related adverse events (AEs) were compared between the groups. Of the 108 eligible patients, 17 (16%), 27 (25%) and 64 (59%) were classified as CRP flare-responders, CRP responders and CRP non-responders, respectively. Objective response rate was higher in CRP flare-responders and CRP responders than in CRP non-responders. Progression-free survival and overall survival were longer in CRP flare-responders and CRP responders than in CRP non-responders. Among CRP flare-responders, patients with low BL CRP levels had a better tumor response and survival than patients with high BL CRP levels. Notably, there was no difference in the incidence of immune-related AEs. In patients with mUC who received pembrolizumab, CRP flare-responders showed favorable oncological outcomes; therefore, BL CRP levels could predict oncological outcomes in CRP flare-responders.

The association of clinical outcomes with posttreatment persistent changes in eosinophils and other white blood cell (WBC) subtypes in patients with advanced urothelial cancer (UC) treated with pembrolizumab after the failure of platinum-based chemotherapy is unclear.BACKGROUND/AIMThe association of clinical outcomes with posttreatment persistent changes in eosinophils and other white blood cell (WBC) subtypes in patients with advanced urothelial cancer (UC) treated with pembrolizumab after the failure of platinum-based chemotherapy is unclear.We retrospectively analyzed 87 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The changes in WBC subtypes from pretreatment were evaluated three and six weeks after pembrolizumab administration. The association between the changes in the WBC subtypes and clinical outcomes was then evaluated using the Kaplan-Meier method and a Cox regression model.PATIENTS AND METHODSWe retrospectively analyzed 87 patients with advanced UC who received pembrolizumab after the failure of platinum-based chemotherapy. The changes in WBC subtypes from pretreatment were evaluated three and six weeks after pembrolizumab administration. The association between the changes in the WBC subtypes and clinical outcomes was then evaluated using the Kaplan-Meier method and a Cox regression model.Among WBC subtypes, significant changes in the absolute (AEC) and relative eosinophil count (REC) and the neutrophil-to-eosinophil ratio (NER) were observed at three and six weeks compared with pretreatment (p<0.001). Multivariable Cox regression analyses revealed that a persistent decrease in AEC and REC and a persistent increase in NER were associated with poor overall survival.RESULTSAmong WBC subtypes, significant changes in the absolute (AEC) and relative eosinophil count (REC) and the neutrophil-to-eosinophil ratio (NER) were observed at three and six weeks compared with pretreatment (p<0.001). Multivariable Cox regression analyses revealed that a persistent decrease in AEC and REC and a persistent increase in NER were associated with poor overall survival.Persistent increase in AEC and REC and decrease in NER in the early phase after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.CONCLUSIONPersistent increase in AEC and REC and decrease in NER in the early phase after pembrolizumab may be significant early predictive markers of improved clinical outcomes in patients with advanced UC receiving pembrolizumab.

To evaluate the association between immune-related adverse events (irAEs) and the clinical outcomes and also between irAEs and the post-treatment changes in the relative eosinophil count (REC) in advanced urothelial carcinoma (UC) patients treated with pembrolizumab. This retrospective study analyzed 105 advanced UC patients treated with pembrolizumab after disease progression on platinum-based chemotherapy between January 2018 and June 2021. The association between the occurrence of irAEs and the efficacy of pembrolizumab was investigated. The change in the REC from before the initiation of pembrolizumab therapy, to three weeks after treatment and the incidence of irAEs were determined. Overall irAEs were associated with a significantly higher objective response rate (ORR) (58.8% vs 25.4%, P<0.001), a longer progression-free survival (PFS) (25.1 months vs 3.1 months, P< 0.001) and overall survival (OS) (31.2 months vs 11.5 months, P< 0.001) compared to patients without irAEs; however, grade ≥3 irAEs were not associated with the ORR (36.4% vs 36.2%, P=0.989), PFS (9.5 vs 5.5 months, P=0.249), or OS (not reached vs 13.7 months, P=0.335). Compared to a decreased REC at 3 weeks after pembrolizumab, an increased relative REC at 3 weeks was not associated with the incidence of any-grade irAEs (32.3% vs 32.5%, P=0.984) or of grade ≥3 irAEs (10.8% vs 10.0%, P=0.900). Multivariate analyses revealed a female sex (P=0.005), Eastern Cooperative Oncology Group Performance Status ≥1 (P=0.024), albumin <3.7 g/dl (P<0.001), decreased REC (3 weeks later) (P<0.001), and the absence of irAEs of any grade (P=0.002) to be independently associated with a worse OS. Patients with irAEs showed a significantly better survival compared to patients without irAEs in advanced UC treated with pembrolizumab. An increased posttreatment REC may be a marker predicting improved clinical outcomes and it had no significant relationship with the incidence of irAEs.