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  • 1
    In: Japanese Journal of Clinical Oncology, Oxford University Press (OUP), Vol. 50, No. 11 ( 2020-10-22), p. 1313-1320
    Abstract: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. Methods We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. Results All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for & gt;5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived & gt;3 years. Conclusion Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.
    Type of Medium: Online Resource
    ISSN: 1465-3621
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1494610-5
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  • 2
    In: Japanese Journal of Clinical Oncology, Oxford University Press (OUP), Vol. 53, No. 9 ( 2023-08-30), p. 837-844
    Abstract: To understand the real-world outcomes for patients with penile cancer in the Kyushu–Okinawa area before the introduction of practice guidelines in Japan. Methods We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu–Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. Results A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08–208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79–10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11–10.1; P = 0.0319) were identified as independent prognostic factors. Conclusions The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.
    Type of Medium: Online Resource
    ISSN: 1465-3621
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1494610-5
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  • 3
    In: International Journal of Clinical Oncology, Springer Science and Business Media LLC, Vol. 26, No. 11 ( 2021-11), p. 2073-2084
    Abstract: Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010–2015. Methods This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan–Meier methodology. Results PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1–positive patients was 30.9 months (95% CI 25.5–35.7) versus 37.5 months (95% CI 34.0–42.6) for PD-L1–negative patients (HR 1.04 [90% CI 0.89–1.22, p  = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1–positive and –negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986). Conclusions This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.
    Type of Medium: Online Resource
    ISSN: 1341-9625 , 1437-7772
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1481773-1
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  • 4
    In: International Journal of Urology, Wiley, Vol. 27, No. 11 ( 2020-11), p. 952-959
    Abstract: To evaluate the efficacy and safety of cabozantinib, through a bridging study to METEOR, in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy. Methods This phase II, open‐label, single‐arm study (ClinicalTrials.gov registration number: NCT03339219) included adult Japanese patients with advanced renal cell carcinoma and measurable disease who had received one or more tyrosine kinase inhibitors. Patients received cabozantinib 60 mg orally once daily while there was clinical benefit, or until unacceptable toxicity or disease progression. The primary end‐point was objective response rate per Response Evaluation Criteria in Solid Tumors Version 1.1. Secondary end‐points included clinical benefit rate (complete or partial response, or ≥8‐week stable disease), progression‐free survival, overall survival and safety. Results Of the 35 patients enrolled, 68.6%, 22.9% and 8.6% had previously received one, two and three prior tyrosine kinase inhibitors, respectively. The median duration of cabozantinib exposure was 27.0 weeks (range 5.1–43.0 weeks). The objective response rate was 20.0% (90% confidence interval 9.8–34.3%), and the clinical benefit rate was 85.7% (95% confidence interval 69.7–95.2%). The 6‐month estimated progression‐free survival was 72.3% (95% confidence interval 53.3–84.6%); the median progression‐free survival and overall survival were not reached. All patients reported adverse events, which were manageable by supportive treatment or dose modification; two patients (5.7%) discontinued therapy due to adverse events. Conclusions The results showed that findings from METEOR can be extrapolated, and that cabozantinib 60 mg/day is a viable treatment option in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy.
    Type of Medium: Online Resource
    ISSN: 0919-8172 , 1442-2042
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2009793-1
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17000-e17000
    Abstract: e17000 Background: Bacillus Calmette–Guérin (BCG) instillation is a key therapy to manage non-muscle invasive bladder cancer (NMIBC). However, intravesical BCG therapy fails in approximately half of patients, leading to recurrence and progression. We aimed to reveal the genetic variations associated with treatment failure after intravesical BCG therapy for NMIBC. Methods: This study included 91 Japanese patients treated with BCG instillation for NMIBC. Genomic DNA was obtained from patient whole blood samples, and a genome-wide association study and genotyping for target regions were performed. The association between genetic variation and treatment failure was analyzed by genome-wide association in 44 patients as the discovery cohort. As a validation study, candidate single nucleotide polymorphisms (SNPs) were examined among 47 patients in the distinct cohort. Results: The genome-wide association study indicated 19 candidate SNPs associated with BCG failure. Consistent results were obtained in six of these SNPs in the validation cohort. Following the combinational use of validated SNPs, 2-gene (rs73520681 and rs61094339) and 4-gene (rs4250, rs11894207, rs73520681, and rs61094339) models successfully predicted treatment failure after intravesical BCG therapy. Conclusions: This study showed that several SNPs were associated with outcome after intravesical BCG therapy in a Japanese population with NMIBC. The combinational use of these SNPs may have value in clinical applications, although this should be confirmed in future studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. LB-153-LB-153
    Abstract: Background: The correlation between PD-L1 expression on tumor-infiltrating immune cells and prognosis in renal cell carcinoma (RCC) has been reported in several studies. Methods: A multicenter retrospective study was carried out to investigate the prognostic value of PD-L1 expression (by the VENTANA SP142 immune cell [IC] scoring method) in primary RCC tumors among patients administered systemic therapy for recurrent or metastatic RCC. The primary endpoint was overall survival (OS), defined as the time from the initiation of first-line treatment to the date of death from any cause. The difference in OS between patients of positive PD-L1 status (IC ≥1%) and those of negative status was compared using a stratified log-rank test at a two-sided level of 0.1, stratified by MSKCC risk and liver metastases. Stratified hazard ratio (HR) and its 90% confidence interval (CI) was estimated by the Cox proportional hazard model. An unstratified analysis and an analysis adjusted by propensity score weighting (PSW) were also conducted. Results: We examined 777 RCC surgical specimens, 770 of which were included for primary analysis (7 were excluded owing to indeterminate PD-L1 status). PD-L1 positive was observed in 315 (40.9%). Immune phenotype that describe the level of T-cell presence and activity within the tumor microenvironment differed between PD-L1-positive vs. -negative groups: Excluded (74.3% vs. 31.6%), Inflamed (16.5% vs. 1.5%), and Desert (9.2% vs. 66.8%). PD-L1-positive status was more common in patients with higher clinical stage, higher Fuhrman grade, and presence of sarcomatoid component. A higher proportion of PD-L1-positive patients had poor prognostic features at the start of first-line therapy: 17.5% vs. 7.3% with ‘poor' MSKCC risk; 29.2% vs. 14.9% with ‘poor' IMDC risk. In line with this, fewer PD-L1-positive patients had good prognostic features at the start of first-line therapy: 11.4% vs. 29 .7% with ‘favorable' MSKCC risk; 10.8% vs. 26.2% with ‘favorable' IMDC risk.The median OS in PD-L1-positive vs. -negative patients was 30.9 months (95%CI: 25.5-35.7) vs. 37.5 months (95%CI: 34.0-42.6). The stratified HR was 1.04 (90%CI: 0.89-1.22, P=0.65), the unstratified HR was 1.21 (90%CI: 1.04-1.40), and the PSW-adjusted HR was 0.99. Subgroup analysis based on MSKCC risk at the start of first-line therapy revealed that there was no significant difference in mOS based on PD-L1-positive vs. -negative status for ‘favorable' (58.6 vs. 59.8 months; HR: 0.92; 95%CI: 0.54-1.56), ‘intermediate' (31.6 vs. 33.5; HR: 1.06; 95%CI: 0.85-1.32) or ‘poor' (6.6 vs 12.8.; HR: 0.89; 95%CI: 0.55-1.43) categories. Conclusion: This study suggested that PD-L1 status on tumor-infiltrating immune cells was not an independent prognostic factor in recurrent or metastatic RCC patients, although positive PD-L1 status was associated with poor prognostic factors. Citation Format: Hirotsugu Uemura, Motohide Uemura, Naoto Sassa, Noboru Nakaigawa, Katsunori Tatsugami, Kenichi Harada, Toshinari Yamasaki, Nobuaki Matsubara, Tamaki Fukuyama, Takuya Yoshimoto, Yuki Nakagawa, Mototsugu Oya, Nobuo Shinohara, Toyonori Tsuzuki. Prognostic value of PD-L1 expression on tumor-infiltrating immune cells in renal cell carcinoma (ARCHERY study) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-153.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    In: Prostate International, Elsevier BV, Vol. 8, No. 1 ( 2020-03), p. 22-26
    Type of Medium: Online Resource
    ISSN: 2287-8882
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2711928-2
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  • 8
    In: Journal of Urology, Ovid Technologies (Wolters Kluwer Health), Vol. 204, No. 1 ( 2020-07), p. 149-156
    Type of Medium: Online Resource
    ISSN: 0022-5347 , 1527-3792
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 5089-5089
    Abstract: 5089 Background: While studies have demonstrated survival benefits of first-line regimens including immuno-oncology agents (IO) in advanced renal cell carcinoma (aRCC), optimal treatment following IO is unknown. In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) versus everolimus in patients (pts) with aRCC, after VEGFR-TKI therapy. The Japanese phase II C2001 study (NCT03339219), targeting a population similar to that of METEOR, showed similar efficacy and safety results. Here, we present a post-hoc pooled analysis of pts who had received prior IO therapy from METEOR and C2001. Methods: A pooled analysis was performed in pts who received 60mg/day of oral cabozantinib once daily enrolled in the METEOR or C2001. Patients were divided into two groups with previous IO treatment (pre-w/ IO subgroup) or without previous IO treatment (pre-w/o IO subgroup). Analyses of ORR, PFS, OS, and safety were performed as measures of clinical outcome in each subgroup. Results: 365 pts (pre-w/ IO subgroup: 33 pts, pre-w/o IO subgroup:332 pts) were included for efficacy analysis and 366 pts (pre-w/ IO subgroup: 33 pts, pre-w/o IO subgroup:333 pts) for safety analysis. Minor differences in baseline characteristics were noted between the analysis subgroups but are not expected to substantially affect efficacy outcomes. The ORR was 21.2% (95% CI: 9.0-38.9%) for pre-w/ IO subgroup, and 17.2% (95% CI: 13.3-21.7%) for pre-w/o IO subgroup. PFS rate and OS rate at 6 months pre-w/ IO was 65.5%, 90.8% and pre-w/o IO was 58.3%, 90.6%, respectively. Although there were some differences in the safety profile, almost all AEs were manageable by dose modifications. There were no differences in AEs associated with IO treatment, such as pneumonitis, endocrinolopathy or infusion related reaction. No new safety signals were noted in any subgroups. Conclusions: Safety and treatment efficacy of cabozantinib were maintained in the pooled analysis of pts from METEOR and C2001 irrespective of prior IO treatment. Funded by Takeda Pharmaceutical Company Limited, Tokyo, Japan. Clinical trial information: NCT03339219, NCT01865747 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 10
    In: International Journal of Clinical Oncology, Springer Science and Business Media LLC, Vol. 28, No. 3 ( 2023-03), p. 416-426
    Abstract: Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment. Methods Japanese patients with RCC who received at least one prior VEGFR-TKI were enrolled and received cabozantinib 60 mg orally once daily. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory analyses included the relationship between plasma protein hepatocyte growth factor (HGF) levels and treatment responses. Results In total, 35 patients were enrolled. The median treatment duration was 58.3 (range 5.1–131.4) weeks. The objective response rate was 25.7% (90% confidence interval [CI] 14.1–40.6). Kaplan–Meier estimate of median progression-free survival was 11.1 months (95% CI 7.4–18.4). The estimated progression-free survival proportion was 73.1% (95% CI 54.6–85.0) at 6 months. Median overall survival was not reached. Adverse events were consistent with those in METEOR and the safety profile was acceptable. Nonresponders to cabozantinib showed relatively higher HGF levels than responders at baseline. Conclusions Updated analyses demonstrate the long-term efficacy and safety of cabozantinib in Japanese patients with advanced RCC after at least one VEGFR-TKI therapy. Responders tended to show lower baseline HGF levels ClinicalTrials.gov Identifier: NCT03339219.
    Type of Medium: Online Resource
    ISSN: 1341-9625 , 1437-7772
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1481773-1
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