Experience and prognostic analysis with avelumab switch maintenance treatment in metastatic urothelial carcinoma.

INTRODUCTION: Avelumab is approved for metastatic urothelial carcinoma (mUC) maintenance therapy and prolongs overall survival (OS). We explored trends related to avelumab treatment of mUC patients. METHODS: A total of 72 patients with mUC treated with first-line chemotherapy, from January 2019 to November 2022, at our affiliated institutions, were analyzed. We compared clinical parameters and the prognosis of patients treated with avelumab (Ave; n=43), because of progression during first-line chemotherapy, with untreated patients (Ave-untreated; n=29). Among the Ave-treated group, we classified patients showing a complete or partial response or stable disease in their best response to avelumab maintenance therapy as avelumab (Ave)-suitable patients; these were retrospectively analyzed. Potential prognostic factors, including the geriatric nutritional risk index (GNRI) for determining patients suitable for Ave, were evaluated. RESULTS: The basic clinical parameters of patients when first-line treatment was initiated were not statistically different between the two groups. The Ave-suitable group (median 26.6 months, 95% confidence interval [CI]: 19.4-not reached [NR]) showed significantly longer median OS after first-line treatment than the Ave-untreated group (median 12.0 months, 95% CI: 7.5-NR) with tolerable adverse events. The cut-off values of prognostic factors were set by receiver operating characteristic curve. Low age and GNRI sustainability revealed as significant prognostic factors for being Ave-suitable both in univariate and multivariate analysis. CONCLUSION: In mUC, avelumab maintenance prolonged OS within tolerable safety profiles. GNRI sustainability may be used as biomarker to predict being Ave-suitable.

GNRI Sustainability during One Cycle of First-Line Chemotherapy as a Prognostic Indicator in Patients with Metastatic Urothelial Carcinoma.

INTRODUCTION: This study evaluated the prognostic value of a sustained high Geriatric Nutritional Risk Index (GNRI) during first-line chemotherapy for patients with metastatic urothelial carcinoma (mUC). METHODS: Between January 2018 and February 2022, 123 patients received platinum-based chemotherapy at Nagoya City University Hospital and affiliated institutions. Of these, 118 eligible patients who showed an Eastern Cooperative Oncology Group performance status (ECOG-PS) between 0 and 2 were retrospectively examined. Based on body mass index and serum albumin levels, GNRI was calculated immediately before and after the first primary chemotherapy cycle. Patients were divided into two groups based on GNRI: GNRI sustained ≥92 in sustainable (n = 63) and GNRI <92 in unsustainable (n = 55) groups, respectively. Clinical outcomes were compared. RESULTS: No significant differences were noted between the two groups for age, gender, cycle of first-line treatment, and type of series of sequential treatments after failure of first-line therapy. Median overall survival from the start of first-line chemotherapy was 30.2 months (95% confidence interval [CI]: 20.9-NA) for sustainable and 12.6 months (95% CI: 9.0-21.2) for unsustainable groups, respectively (p < 0.05). Multivariate analysis identified ECOG-PS:2 and fatigue, an adverse event, as independent predictors of unsustainable GNRI transition (95% CI: 1.29-90.6, odds ratio [OR]: 10.8; 95% CI: 1.06-26.9, OR: 5.34, respectively). CONCLUSION: Sustaining a high level of GNRI was an important prognostic indicator in patients with mUC receiving first-line chemotherapy. Appropriate intervention for controlling adverse events, including fatigue, may enhance physical strength during cancer treatment.

Chronological transition in outcome of second-line treatment in patients with metastatic urothelial cancer after pembrolizumab approval: a multicenter retrospective analysis.

BACKGROUND: After first-line chemotherapy failure, metastatic urothelial carcinoma (mUC) patients undergo pembrolizumab (PEM) or gemcitabine and docetaxel (GD) therapy. We retrospectively investigated outcomes of second-line GD or PEM for mUC patients. METHODS: A total of 198 mUC patients from Nagoya City University and affiliated hospitals who received second-line treatment were grouped according to immune check point inhibitor (ICI) availability: Groups A (pre-ICI: n = 104) and B (post-ICI: n = 94). We compared clinical outcomes using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses assessed potential prognostic factors for overall survival (OS). RESULTS: Median OS was significantly longer for Group B [median 13.6 months, 95% confidence interval (CI): 7.6-17.6] than A (7.6 months, 5.3-8.8). By sub-group analysis, patients received no additional treatment (Naïve, n = 70), or PEM or GD (Salvage, n = 24) in Group B, with median OS of Naïve and A groups similar. Compared to the Salvage group, significant differences in OS were observed (median 7.6 months, 95% CI 5.3-8.8; Group A, 7.6 months, 4.7-13.8; Naïve, 25.7 months, 14.0-31.0; p < 0.01). For the Salvage group, OS for sequential treatment of GD-salvage PEM and PEM-salvage GD patients was similar (p = 0.10). Multivariate analysis showed a low neutrophil-to-lymphocyte ratio (NLR) and high geriatric nutritional risk index (GNRI) as significant prognostic factors affecting long OS [95% CI 1.12-3.45, hazard ratio (HR): 1.97; 95% CI 0.24-0.71, 0.41, respectively]. CONCLUSION: Second-line GD or PEM therapy for mUC patients showed equivalent survival benefits. GNRI and NLR are prognostic biomarkers for survival outcome.

Low Geriatric Nutritional Risk Index as a Poor Prognostic Marker for Second-Line Pembrolizumab Treatment in Patients with Metastatic Urothelial Carcinoma: A Retrospective Multicenter Analysis.

BACKGROUND: We evaluated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in second-line pembrolizumab (PEM) therapy for patients with metastatic urothelial carcinoma (mUC). PATIENTS AND METHODS: From January 2018 to October 2019, 52 mUC patients, treated previously with platinum-based chemotherapy, underwent second-line PEM therapy. Peripheral blood parameters were measured at the start of treatment: serum neutrophil-to-lymphocyte ratio (NLR), serum albumin, serum C-reactive protein (CRP), and body height and weight. PEM was intravenously administered (200 mg every 3 weeks). The patients were organized into two groups based on their GNRI (<92 [low GNRI] and ≥92 [high GNRI]), and the data were retrospectively analyzed. Adverse events (AEs) were evaluated and imaging studies assessed for all patients. Analyses of survival and recurrence were performed using Kaplan-Meier curves. Potential prognostic factors affecting cancer-specific survival (CSS) were assessed by univariate and multivariate Cox regression analyses. RESULTS: patients' baseline characteristics, except for their BMI and objective response rate, did not significantly differ between the two groups. The median total number of cycles of PEM therapy was significantly higher for the high-GNRI group (n [range]: 6 [2-20] vs. 3 [1-6]). The median CSS with second-line PEM therapy was 3.6 months (95% confidence interval [CI]: 2.5-6.1) and 11.8 months (95% CI: 6.2-NA) in the low-GNRI and the high-GNRI group (p < 0.01), respectively. Significant differences in CSS between the low- and high-CRP or -NRL groups were not found. Multivariate Cox proportional-hazards regression analysis revealed that a poor Eastern Cooperative Oncology Group performance status, visceral metastasis, and a low GNRI were significant prognostic factors for short CSS (95% CI: 1.62-6.10, HR: 3.14; 95% CI: 1.13-8.11, HR: 3.03; 95% CI: 1.32-8.02, HR: 3.25, respectively). Of the AEs, fatigue showed a significantly higher incidence in the low-GNRI group. CONCLUSIONS: For mUC patients receiving second-line PEM therapy, the GNRI is a useful predictive biomarker for survival outcome.

C-Reactive Protein Is a Potential Prognostic Marker in Patient with Advanced or Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multi-Center Retrospective Study.

BACKGROUND: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. METHODS: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. RESULTS: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68-79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0-not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. CONCLUSIONS: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients.

Modified Glasgow Prognostic Score 2 as a Prognostic Marker in Patients With Metastatic Urothelial Carcinoma.

BACKGROUND/AIM: Predicting the prognosis of metastatic urothelial carcinoma (mUC) patients is needed for clinical decisions. We examined the value of a modified Glasgow prognostic score (mGPS) as a predictive marker for mUC patients. PATIENTS AND METHODS: In a multicenter study, 68 mUC patients received short hydration gemcitabine/cisplatin (shGC) and 74 received pembrolizumab (PEM). Patients were allocated according to mGPS. Progression-free (PFS) and cancer-specific (CSS) survival were examined. RESULTS: Higher mGPS reflected poorer PFS and CSS in shGC (p=0.03, p<0.0001, respectively) and PEM (p=0.02, p<0.001, respectively) patients. PFS for the high mGPS group was longer than that of the low mGPS group in the two cohorts (p <0.0001 for both), with similar CSS results (p<0.0001 and p<0.001, respectively). Multivariate analyses revealed high mGPS was a risk factor for poor CSS in both cohorts (HR=3.55, p<0.001, and HR=2.21, p<0.01, respectively). CONCLUSION: In the mUC patients receiving shGC or PEM, mGPS was a predictive prognostic marker.

Complete response of renal cell carcinoma with an inferior vena cava tumor thrombus and lung metastases after treatment with nivolumab plus ipilimumab.

In recent years, immune checkpoint inhibitors have become the most important drugs for treating renal cell carcinoma. In combination with performing nephrectomies, tyrosine kinase inhibitors have been used as neoadjuvant therapy, as they reduce the size of a primary renal mass and cause the disappearance of metastatic lesions. However, there are only a few reports on immune checkpoint inhibitors as neoadjuvant therapy. Herein, we report a case of renal cell carcinoma with multiple lung metastases and an inferior vena cava tumor thrombus that showed a complete response via radical nephrectomy after nivolumab plus ipilimumab. A 47-year-old man was diagnosed with renal cell carcinoma with multiple lung metastases and inferior vena cava tumor thrombus. After four treatment cycles of nivolumab plus ipilimumab and five cycles of nivolumab, we performed radical nephrectomy and resection of the thrombus tumor by excising a part of the inferior vena cava. The pathological diagnosis had no residual tumor. To our knowledge, this is the first case of complete disappearance of all malignant cells. Immunostaining of the primary renal mass revealed strong positivity for CD4 and CD8. The patient has been followed up without additional treatment for 8 months, but no recurrence has been observed. We suggest the use of nivolumab plus ipilimumab as neoadjuvant therapy. However, physicians should consider the possibilities of immune-related adverse events.

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis.

BACKGROUND: The objective of this study was to evaluate the efficacy of a combination of gemcitabine and docetaxel (GD) as a second-line treatment for elderly patients with metastatic urothelial carcinoma (mUC). PATIENTS AND METHODS: A total of 122 patients with mUC who were previously treated with platinum-based chemotherapy received second-line GD therapy from July 2010 to June 2016. This consisted of 800 mg/m2 gemcitabine and 40 mg/m2 docetaxel on days 1 and 8 in each 21-day cycle. Using pooled cumulative data, we divided patients into the following three groups based on age: <65 years (Group A), from 65 to 74 years (Group B), and ≥75 years (Group C), and then the data were retrospectively analyzed. All patients were evaluated for treatment-related toxicities and assessed at every cycle by imaging studies. Kaplan-Meier curves were used for survival and recurrence analyses. Furthermore, potential prognostic factors for progression-free survival (PFS) and overall survival (OS) were assessed via univariate and multivariate Cox regression analyses. RESULTS: The median follow-up period was 8.2 months (range: 2.1-100). The median number of treatment cycles was three (range: 1-16) in Group A, three (1-15) in Group B, and two (1-11) in Group C. The objective response rate was not significantly different between the three groups. In addition, PFS and OS from the start of second-line GD therapy were also not significantly different. According to univariate and multivariate analyses of the second-line GD-treated cohort, a good performance status was the only prognostic factor for PFS and OS. In Group C, myelosuppression including predominant neutropenia and anemia, fatigue, and nausea were the main common adverse events. However, the incidence of neutropenia and a reduction in platelets were not significantly different between the three groups. Treatment-related deaths did not occur in this study. CONCLUSION: In this study, GD combination therapy as a second-line treatment for mUC resulted in favorable tumor responses and few treatment-related toxicities, even among elderly patients.