Abstract
Introduction
Metastases from renal cell carcinoma develop in various organs. However, the breadth of discrepancy in response to immune checkpoint inhibitors across tumor sites within the ...same individual remains unclear.
Patients and methods
We reviewed 50 patients with metastatic renal cell carcinoma who had target lesions at multiple sites and received nivolumab monotherapy (n = 36) or nivolumab plus ipilimumab (n = 14). When the best overall response in tumor burden increased at one site but decreased at other sites, the response was defined as a dissociated response. The response was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1, and patients who met the definition of dissociated response were categorized as dissociated response. The rate of dissociated response and prognosis were evaluated.
Results
Eight of 36 (22%) and 4 of 14 (29%) patients treated with nivolumab and nivolumab plus ipilimumab were categorized as having dissociated response, respectively. The median overall survival of the patients treated with nivolumab was 20.2 months for those with a partial response, 6.8 months for those with stable disease, and 13.2 months for those with progressive disease, while dissociated response was not reached. There was no significant difference in the median overall survival between patients categorized as having progressive disease and those with dissociates response (P = 0.224).
Conclusion
A certain proportion of patients with metastatic renal cell carcinoma show dissociated response when treated with immune checkpoint inhibitors. The prognosis of patients with dissociated response and progressive disease was not shown to be significantly different.
To assess the characteristics of biochemical recurrence in the late period (>5 years after radical prostatectomy) and the differences in the predictors of biochemical recurrence in different periods, ...we conducted a multicenter retrospective study.
We reviewed 478 men who underwent radical prostatectomy for clinically localized prostate cancer. All of the patients were followed up for at least 5 years. The cohort was then divided into three groups; no recurrence group, recurrence <5 years after surgery group and recurrence ≥5 years after surgery group. The background characteristics of each group were compared using the χ2 test. A Cox multivariate regression analysis was performed to determine the predictors of biochemical recurrence in each period.
Biochemical recurrence occurred in 135 men. In 113 (84%) of the patients, biochemical recurrence occurred at <5 years after surgery; in 22 (16%), it occurred at ≥5 years after surgery. The proportion of men with a low preoperative prostate-specific antigen level was significantly larger in the latter group (P = 0.0023). A preoperative prostate-specific antigen level and a positive surgical margin were significant predictors of biochemical recurrence at <5 years after surgery (hazard ratio: 1.03 and 3.20). A positive surgical margin was also a significant predictor of biochemical recurrence at ≥5 years after surgery (hazard ratio: 3.03); however, a high preoperative prostate-specific antigen level was not.
Biochemical recurrence occurred at ≥5 years after surgery in 16% of the patients. A positive surgical margin predicted biochemical recurrence in both the early and late periods.
Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of ...enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease. We retrospectively evaluated consecutive patients with advanced lower and upper urinary tract cancer who received EV after platinum-based chemotherapy and immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with SUC. We identified 44 and 18 patients with PUC and SUC, respectively. Squamous differentiation was the most common subtype element, followed by glandular differentiation and sarcomatoid subtype. Although patients with SUC had a comparable ORR to those with PUC, the duration of response for SUC was short. Patients with SUC had poorer PFS than those with PUC; however, no significant difference was observed in OS. Multivariate analysis revealed that SUC was significantly associated with shorter PFS. Although the response of metastatic SUC to EV was similar to that of PUC, SUC showed faster progression than PUC.
This multi-institutional study aimed to identify prognostic factors for cabazitaxel treatment of castration-resistant prostate cancer (CRPC). This study included 74 Japanese patients with CRPC who ...were treated with cabazitaxel between 2014 and 2017. Associations between clinicopathological factors including serum markers and progression-free survival (PFS) and overall survival (OS) were investigated. On multivariate analysis, high Gleason score ≥9 vs. ≤7; hazard ratio (HR), 95% confidence interval (CI): 2.00 (1.01-4.34); P = 0.047, presence of pain HR, 95% CI: 2.02 (1.14-3.58); P = 0.016, and lactate dehydrogenase (LDH) level HR, 95% CI: 47.31 (3.79-577.49); P = 0.0019 were significantly associated with PFS. Similarly, number of docetaxel cycles HR, 95% CI: 0.050 (0.0037-0.45); P = 0.0057, performance status ≥2 vs. 0; HR, 95% CI: 5.07 (1.57-16.24); P < 0.0001, and LDH level HR, 95% CI: 2946 (50-420994); P = 0.0001 were significantly associated with OS. This study showed that LDH level is robustly prognostic for both PFS and OS in cabazitaxel chemotherapy for CRPC.
Objective
This study aimed to reveal the efficacy and safety profiles of 4-weekly cabazitaxel in patients with castration-resistant prostate cancer (CRPC).
Methods
The study included 62 Japanese ...patients who were treated for CRPC with ≥ 2 courses of cabazitaxel between 2014 and 2017. The oncological outcomes and adverse events were compared between 16 (25.8%) and 46 (74.2%) men who were treated with standard 3-weekly and alternative 4-weekly regimens, respectively.
Results
The prostate-specific antigen (PSA) response was comparable between the 3-weekly and 4-weekly regimens (median interquartile range: − 9.9% − 64.5 to 13.0% and − 30.7% − 52.8 to 10.9%,
P
= 0.89), respectively. For patients on the 4-weekly regimen, the risks of progression (hazard ratio HR, 95% confidence interval CI 1.27, 0.71–2.43,
P
= 0.44), treatment failure (HR, 95% CI 0.84, 0.48–1.55,
P
= 0.57) and any-cause mortality (HR, 95% CI 1.09, 0.58–2.17,
P
= 0.79) were comparable to those for patients on the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens.
Conclusions
3-weekly and 4-weekly regimens of cabazitaxel showed similar efficacy and safety profiles in a real-world clinical setting. These data suggest that a 4-weekly regimen may be acceptable for selected patients.
Pembrolizumab has been available for the treatment of radical resectable urothelial carcinoma (UC) when it is exacerbated after chemotherapy since December 2017 in Japan. However, the efficacy of ...chemotherapy for cases progressing after pembrolizumab is unclear. The present study compared the outcomes and toxicities in patients with metastatic UC after failure of platinum-based chemotherapy and pembrolizumab, who were selected to receive paclitaxel and carboplatin (TC) chemotherapy, with those in patients who received the best supportive care (BSC). A total of 36 patients received pembrolizumab for metastatic UC at four institutions between January 2018 and August 2019. Of the 21 patients who progressed after pembrolizumab, 7 received TC chemotherapy (TC group) and 14 selected BSC (BSC group). The median observation period was 4.1 months. The 7 aforementioned patients who received TC chemotherapy (4 male and 3 female; median age, 62 years; range, 57-79 years) were analyzed in the present study. The ECOG performance status was 0 in three patients, 1 in one patient, 2 in two patients and 3 in one patient. Two patients had upper urinary tract UC, two had bladder UC and three had both types of UC. Six patients had visceral metastasis. The number of chemotherapy regimens before pembrolizumab was one in four patients, two in two patients and three in one patient. The objective response rate was 28.6% (partial response, 2 patients; stable disease, 4 patients; progressive disease, 1 patient), the median progression-free survival time was 3.4 months and the median overall survival time was 10.9 months (vs. 2.7 months in BSC group; P=0.0156). Although grade ≥3 adverse events developed in five patients, there were no treatment-associated deaths. The present results suggested that TC chemotherapy may be a preferred option for patients who require aggressive treatment after the failure of platinum-based chemotherapy and pembrolizumab.
There is little data on the outcome of cabazitaxel (CBZ) treatment of elderly patients with castration-resistant prostate cancer (CRPC). This study assessed the efficacy and safety of CBZ ...chemotherapy in patients with CRPC aged 75 years or older in a multiinstitutional study.
We retrospectively reviewed the 74 patients with CRPC treated with CBZ enrolled in 10 institutions. Clinicopathological backgrounds, prognosis including prostate-specific antigen decline, time to treatment failure, progression-free survival, overall survival, and safety profiles were compared between younger (<75 years) and elder (≥75 years) patients.
In total, 74 patients were enrolled; 50 patients were younger than 75 years and 24 were ≥75 years. Clinicopathological characteristics were comparable between younger and elder patients, with the exception of serum albumin values at the time of CBZ treatment. The median prostate-specific antigen decline in younger and elder men was −8.8% and −32.3% from baseline, respectively. The median time to treatment failure, progression-free survival, and overall survival for younger and elder men were 0.24 and 0.33 years, 0.23 and 0.43 years, and 0.69 and 1.17 years, respectively. In addition, safety profiles were comparable between younger and elder patients.
This multiinstitutional study suggests that patients with CRPC aged 75 years or older eligible for CBZ treatment can be treated safely and with noninferior efficacy compared with those younger than 75 years.
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