Durvalumab and bladder

BACKGROUND: Only 20 percent of renal and bladder cancer patients will show a significant response to immune checkpoint inhibitor (ICI) therapy, and no test currently available accurately predicts ICI response. METHODS: We developed an "immunotumoroid" cell model system that recapitulates the tumor, its microenvironment, and necessary immune system components in patient-derived spheroids to enable ex vivo assessment of tumor response to ICI therapy. Immunotumoroids were developed from surgically resected renal cell carcinomas and bladder carcinomas selected for high tumor-infiltrating lymphocytes (TILs) and survived more than a month without media exchange...

Objectives: Immune checkpoint inhibitor (ICI) is an important treatment option for metastatic urothelial carcinoma (mUC) patients. A lot of clinical evidence proved the survival benefits of ICI, but cost-effectiveness of the treatment remains unclear. This study evaluates the cost-effectiveness of the ICIs treatment in different sequences among mUC patients. Methods: We retrospectively analyzed mUC patients who had been treated at our hospital between January 2016 and December 2020. These patients received chemotherapy with or without ICI treatment (Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, or Avelumab)...

OBJECTIVES: To assess the safety of sub-urothelial injection of durvalumab and examine the impact on tissue and circulating immune cell populations. PATIENTS AND METHODS: The patients were chemotherapy and immunotherapy naïve (bacille Calmette-Guérin allowed) with non-metastatic muscle-invasive bladder cancer or non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal saline, injected at 25 locations (25 × 1 mL injections), at least 2 weeks before RC...

OBJECTIVE: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy. PATIENTS AND METHODS: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer...

CONTEXT: The optimal therapeutic agent with respect to metastatic sites is unclear in advanced urothelial carcinoma (UC). OBJECTIVE: To investigate the metastatic organotropism differential treatment response in patients with advanced or metastatic UC. EVIDENCE ACQUISITION: A systematic search and network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The primary endpoints of interest were the objective response rate, overall survival (OS), and progression-free survival with respect to different metastatic sites...

Blockade of CTLA-4 by tremelimumab combined with anti-PD-L1 durvalumab and chemotherapy provided increased antitumor activity and long-term survival benefits in first-line metastatic non-small-cell lung cancer (mNSCLC) in the Phase III POSEIDON study. We performed population pharmacokinetic modeling for tremelimumab using data from 1605 patients across six studies (including POSEIDON) in multiple tumors (lung cancer, bladder cancer, malignant mesothelioma, and other solid tumors), and identified a 2-compartment model with linear and time-varying clearance for tremelimumab...

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer...

PURPOSE: The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab. PATIENTS AND METHODS: SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC...

PURPOSE: Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive carcinoma in situ (CIS). PATIENTS AND METHODS: Patients with BCG-unresponsive CIS-containing NMIBC received durvalumab IV at 1,500 mg every 4 weeks for up to 12 months. The primary endpoint was complete response (CR) rate at month 6, defined by negative cystoscopy, urine cytology, and absence of high-grade recurrence on bladder mapping biopsy...

To investigate the safety and efficacy of "quadri-combination" therapy including maximal transurethral resection of bladder tumor (mTURBT), combined with systemic chemotherapy and immunotherapy, concurrent radiotherapy, and immune maintenance therapy. The clinical data of 8 patients with bladder cancer who could not tolerate or refused radical cystectomy at the Department of Urology, Peking University Cancer Hospital from November 2019 to October 2021 were retrospectively analyzed. There were 5 males and 3 females with a mean age of 69 years...

BACKGROUND: Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetic and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveal a highly prevalent molecular profile predictive of response to PD-1/PD-L1 ICIs. A clinical blood test based on a set of eight (8) 3D genomic biomarkers has been developed and validated on the basis of an observational trial to predict response to ICI therapy...

BACKGROUND: Patients with bladder cancer (BC) who are cisplatin ineligible or have unresectable disease have limited treatment options. Previously, we showed targeting programmed death-ligand 1 (PD-L1) with durvalumab (durva) and radiation therapy (RT) combination was safe in BC. We now report results from a phase II study evaluating the toxicity and efficacy of durva and RT in localized BC. METHODS: This is a single-arm, multi-institutional phase II study; N=26...

BACKGROUND: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. OBJECTIVE: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). DESIGN, SETTING, AND PARTICIPANTS: A multicenter phase 1 trial was conducted at community and academic sites...

BACKGROUND: The primary objective of this phase I, open-label trial was to assess safety and tolerability of tremelimumab monotherapy and combination therapy with durvalumab in Japanese patients with advanced cancer. Tremelimumab is a fully human monoclonal antibody against CTLA-4 in clinical trials; durvalumab is a monoclonal antibody against PD-L1 for the treatment of bladder and lung cancer. METHODS: In part 1, tremelimumab 3 or 10 mg/kg was given every 4 weeks (Q4W) for 6 doses, and thereafter every 12 weeks until discontinuation (n = 8); subsequently tremelimumab 10 mg/kg Q4W for 6 doses/Q12W and thereafter until discontinuation was administered in 41 patients with malignant pleural or peritoneal mesothelioma (MPM)...

Biliary tract cancers (BTC) are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them...

In contrast with other strategies, immunotherapy is the only treatment aimed at empowering the immune system to increase the response against tumor growth. Immunotherapy has a role in the treatment of bladder cancer (BC) due to these tumors' high tumor mutational burden (TMB) and mostly prominent immune infiltrate. The therapy or combination has to be adjusted to the tumor's immunobiology. Recently, a new class of immunotherapeutic agents, immune checkpoint inhibitors (ICI), has shown potential in increasing treatment chances for patients with genitourinary cancers, improving their oncological outcomes...

CONTEXT: Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void. OBJECTIVE: To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1st and 2nd line IO-based regimens...

Immune checkpoint inhibitors have revolutionized the treatment of bladder urothelial cancers and have wide application in almost all disease states. Although several drugs have initially been shown to be beneficial in the second-line metastatic setting, there are still ongoing controversies and debate, including voluntary withdrawals of durvalumab and atezolizumab, along with the approval of agents in the first-line setting in the cisplatin-ineligible state based on inconsistent confirmatory phase III trials...

Background and Objectives : Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods : A literature search was performed on Medline and clinical trials databases, using the terms: "bladder cancer" OR "urothelial carcinoma", AND "neoadjuvant immunotherapy" OR "preoperative immunotherapy"...

Therapies based on the use of immune checkpoint inhibitors (ICIs), such as nivolumab, pembrolizumab, ipilimumab, atezolizumab, avelumab, and durvalumab, have proven effective in the treatment of metastatic urological neoplasms. Recently, it has been hypothesized that the use of this type of treatment prior to surgery could lead to an increased difficulty in renal and bladder surgeries. The literature concerning this topic, however, is still scarce and non-consensual. In our systematic review, we used the PRISMA guidelines methodology to search the pertinent literature available up to June 18, 2020 in PubMed...