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Metastatic Urothelial - Crossref

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Last Updated: 22 April 2022

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Neoantigen-specific CD8 T cell responses in the peripheral blood following PD-L1 blockade might predict therapy outcome in metastatic urothelial carcinoma

Abstract T cell reactivity against tumor mutation-based neoantigens has been shown to enhance antitumor immunity that has been induced by immune checkpoint blockade. Patients with controlled disease in metastatic urothelial carcinoma treated with PD-blockade are characterized by increased numbers of neoantigen-reactive CD8+ T cell populations during pre-treatment to 3-weeks post-treatment. Here we show that patients with controlled disease differ from those with progressive disease in metastatic urothelial carcinoma treated with PD-L1-blockade. Following ICB, the review provides insight into NART characteristics; the research shows that early-stage NART expansion and activation are associated with responses to ICB in patients with mUC.

Source link: https://doi.org/10.1038/s41467-022-29342-0


Erdafitinib in locally advanced/metastatic urothelial carcinoma with certain FGFR genetic alterations

Erdafitinib was the first FGFR inhibitor approved for the treatment of metastatic UC, providing adequate clinical integrity and a consistent safety profile in a population with limited or no therapeutic options. Although results from comparative phase II and III trials are needed to determine the toxicity of erdafitinib in various clinical settings, there are still unanswered questions regarding a common class effect of FGFR inhibitors and hypersporemia.

Source link: https://doi.org/10.2217/fon-2021-1151


ATLANTIS: An adaptive multi-arm phase II trial of maintenance targeted therapy after chemotherapy in advanced/metastatic urothelial cancer - Enzalutamide arm v1

Background: Metastatic urothelial cancer is the eighth most common cause of cancer death in the United Kingdom. Patients usually relapse within 6 months after completion, although MUC is initially sensitive to chemotherapy. ATLANTIS is a randomised phase II biomarker controlled umbrella screening trial of maintenance therapy in biomarker specific subgroups of patients with advanced or metastatic urothelial cancer. If each subgroup trial is concluded or a new novel drug subgroup is introduced, the relevant novel drug-specific appendices will be updated. Prior to randomization, central tissue biomarker testing for biomarker will take place. Objectives: The trial will determine whether maintenance targeted therapy after chemotherapy will prolong disease-related therapy, with treatment selection based on biomarker expression, delays time to progression, and overall survival for patients with MUC.

Source link: https://doi.org/10.17504/protocols.io.e6nvwkb79vmk/v1


ATLANTIS: An adaptive multi-arm phase II trial of maintenance targeted therapy after chemotherapy in advanced/metastatic urothelial cancer - Cabozantinib arm v1

Background: Metastatic urothelial cancer is the eighth most common cause of cancer deaths in the United Kingdom. ATLANTIS is a randomized phase II biomarker-directed umbrella screening trial of maintenance therapy in biomarker defined subgroups of patients with advanced or metastatic urothelial cancer. As each individual subgroup trial concludes or a new novel drug subgroup is launched, the relevant novel drug-specific appendices will be updated. Prior to randomization, central tissue biomarker testing for biomarker will be carried out. Objectives: The trial will determine whether maintenance targeted therapy after chemotherapy will work, with treatment pick based on biomarker expression, delays time to progress, and overall survival for patients with MUC. progression since first line therapy depicts the transition to the disease's lethal stage and often the need for further cytotoxic therapy.

Source link: https://doi.org/10.17504/protocols.io.81wgb6ro3lpk/v1


ATLANTIS: An adaptive multi-arm phase II trial of maintenance targeted therapy after chemotherapy in advanced/metastatic urothelial cancer - Rucaparib arm v1

Background: Metastatic urothelial cancer is the eighth most common cause of cancer death in the United Kingdom. Although MUC is first sensitive to chemotherapy, patients often relapse within 6 months of completion. ATLANTIS is a randomised phase II biomarker-directed umbrella screening study of maintenance therapy in biomarker specific subgroups of patients with advanced or metastatic urothelial cancer. Once each subgroup's trial concludes or a new novel drug subgroup is announced, the relevant novel drug-specific appendices will be updated. Objectives: The trial will determine if maintenance targeted therapy after chemotherapy is worth it, with treatment pick based on biomarker expression, delays time to progression, and overall survival for patients with MUC. progression after first line therapy has depicted the transition to the disease's lethal phase of the disease and the need for more cytotoxic therapy.

Source link: https://doi.org/10.17504/protocols.io.b4e9qth6


Case Report: Good responsiveness of metastatic sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation to immune checkpoint inhibitor after radical surgery and chemotherapy

BACKGROUND urothelial carcinoma with chondrosarcomatous differentiation in the ureter has poor prognosis and is a rare histological manifestation of ureteral cancer. After radical surgery and unsuccessful adjuvant chemotherapy, we present a case of well-controlled metastatic SUCCD treated with an immune checkpoint inhibitor. The patient, a 68-year-old male with previous treatment history of cT1-staged esophageal squamous cell carcinoma, referred to the Urology department for a right hydronephroureterosis complicating an intraureteral enhancing mass, complicating an intraureteral enhancing mass. With infiltration of the renal capsule's periureteric fat and renal parenchyma, the renal capsule's final diagnosis was a pT3N0 sarcomatoid urothelial carcinoma localized at the right distal ureter and right renal calyx. Despite the unfavorable outcome of the pathology, the recurrent metastatic SUCCD showed good reaction to the immune checkpoint inhibitor after failed therapy with radical surgery and first line chemotherapy.

Source link: https://doi.org/10.12688/f1000research.27244.2


Case Report: Good responsiveness of metastatic sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation to immune checkpoint inhibitor after radical surgery and adjuvant chemotherapy

Background: Sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation in the ureter has a poor prognosis and is a rare histological manifestation of ureteral cancer. Urothelial carcinomas account for the vast majority of ureteral cancers. After radical surgery and failed adjuvant chemotherapy, we report a case of well-controlled metastatic SUCCD treated with an immune checkpoint inhibitor. The patient, a 68-year-old male with previous cure history of cT1-staged esophageal squamous cell carcinoma, referred to the urology department for a right hydronephroureterosis complicating an intraureteral augmentation mass, complicating an intraureteral augmentation mass. The renal capsule's periureteric fat and renal parenchyma were among the renal capsule's sarcomatoid urothelial carcinomas, which was found within the right distal ureter and right renal calyx with infiltration of the periureteric fat and renal parenchyma of the renal capsule. Despite the pathological's unfavorable outcomes, the recurrent metastatic SUCCD showed good response to the immune checkpoint inhibitor after failed therapy with radical surgery and first line chemotherapy.

Source link: https://doi.org/10.12688/f1000research.27244.1


Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

We retrospectively reviewed 136 patients with pemozinab for unresectable or metastatic urothelial carcinoma. According to the Response Evaluation Criteria in Solid Tumors version 1. 1 as follows: complete response, partial response, stable disease, and progressive disease. Patients with bone metastases received less. Patients with MR may need to be treated as well as patients with pure PD.

Source link: https://doi.org/10.3390/cancers14071735


Abstract 1361: Population pharmacokinetic modeling of avelumab to support flat dosing in patients with locally advanced or metastatic urothelial carcinoma

BACKGROUND Avelumab is a human IgG1 monoclonal antibody that has been approved in the United States for second-line locally developed or metastatic urothelial carcinoma and first-line maintenance therapy of patients with UC who have not progressed with first-line platinum-containing chemotherapy. METHODS: In four clinical studies, PK results from avelumab-treated patients with solid tumors were included. For analysis of PK and immunogenicity, blood samples from 1LM-UC patients were collected predose and immediately before infusion from cycles 1 to 13. Following 10-mg/kg Q2W and 800-mg Q2W single-dose and steady-state exposure studies in the 1LM-UC population, a single-dose and steady-state exposure metrics predicted in the 1LM-UC population were compared to simulation exposure tests conducted in the 800-mg Q2W flat-dosing regimen. The Avelumab PK values in 1LM-UC patients were similar to those in other patients with solid tumors, and were consistent with those in other patients with solid tumors. From baseline clearance in 1LM-UC patients grouped by immunogenicity or PD-L1 status, they ranged from 0. 0257 to 6. 9%, respectively, with a ranged from 0. 0257 to 6. 9%. The results of post hoc pre-dose and steady-state avelumab exposures closely matched with simulations of patients with solid tumors receiving avelumab 800 mg Q2W. CONCLUSIONS: The popPK report found that avelumab PK in the 1LM-UC patient population is consistent with the previously described condition. Neither immunogenicity nor PD-L1 status had clinically significant effects on avelumab clearance, but no improvement in avelumab clearance over time was found.

Source link: https://doi.org/10.1158/1538-7445.am2021-1361


Abstract 1360: Exposure-response safety analysis of avelumab in patients with locally advanced or metastatic urothelial carcinoma

Abstract BACKGROUND: Avelumab is a human IgG1 monoclonal antibody that has been given in the United States for second-line locally developed or metastatic urothelial carcinoma treatment of patients with UC who have not progressed with first-line platinum-containing chemotherapy. paraphrasedoutput:METHODS: Following 10-mg/kg every two weeks dosing in 1LM-UC patients, the derived based on population pharmacokinetic results. RESULTS: In the analyses, a total of 344 1LM-UC patients treated with avelumab were included. Any-grade IRR showed a potentially confounded inverse correlation with avelumab administration, a pattern observed in patients with advanced renal cell carcinoma. The results of this review support the use of the flat-dosing treatment for 1LM-UC patients due to the similarity in avelumab exposures between the flat 800-mg Q2W and weight-based 10-kg dosing. [abstract]: Avelumab in patients with locally advanced or metastatic urothelial carcinoma, according to an exposure-response safety study [abstract].

Source link: https://doi.org/10.1158/1538-7445.am2021-1360

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions