scholarly journals Atezolizumab in patients with renal insufficiency and mixed variant histology: analyses from an expanded access program in platinum-treated locally advanced or metastatic urothelial carcinoma

2020 ◽  
Vol 8 (2) ◽  
pp. e000419
Author(s):  
Jean Hoffman-Censits ◽  
Sumanta Pal ◽  
Constanze Kaiser ◽  
Beiying Ding ◽  
Joaquim Bellmunt
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Urothelial Carcinoma ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
Expanded Access Program ◽  
Metastatic Urothelial Carcinoma ◽  
Variant Histology ◽  
Access Program ◽  
Mixed Variant

BackgroundAtezolizumab is a treatment for locally advanced/metastatic urothelial carcinoma (mUC). However, its use in patients with renal insufficiency or UC with mixed variant histology (MVH) is not well characterized.ObjectiveTo report efficacy and safety of atezolizumab in these special subpopulations from an expanded access program (EAP).Design, setting, and participantsA total of 218 patients were enrolled at 36 US study sites (November 2015–August 2016), and the trial ended following the approval of atezolizumab by the US Food and Drug Administration. This post hoc analysis investigated outcomes in specific study subgroups.InterventionAtezolizumab 1200 mg was administered intravenously every 3 weeks until loss of clinical benefit, unacceptable toxicity, death, consent withdrawal, decision to discontinue, commercial availability, or study closure.Outcome measurements and statistical analysisResponse Evaluation Criteria in Solid Tumors V.1.1 responses and safety were evaluated by baseline renal function and histology.Results and limitationsObjective responses occurred in 0/6 (0%), 4/19 (21%), 1/27 (3.7%), and 12/62 (19%) of evaluable patients with creatinine clearance (CrCl) <30, 30–45, 45–60, and ≥60 mL/min, respectively, and stable disease was seen in three patients with CrCl <30 mL/min. Objective responses were seen in 13/102 patients (13%) with urothelial carcinoma (UC) histology only and in 4/12 patients (33%) with UC with MVH. Treatment-related adverse event frequencies ranged from 35% to 54% across the earlier indicated CrCl subgroups and they were also similar in patients with pure UC or UC with MVH (46%).ConclusionsIn this EAP mUC subgroup analysis, clinical benefit of atezolizumab occurred in patients with compromised renal function or MVH UC tumors. Safety was comparable across subgroups.Patient summaryWe examined the efficacy and safety of atezolizumab for UC in certain patients participating in an EAP. We found that responses to atezolizumab occurred, and safety was similar, in most patient subgroups with varying levels of kidney functioning or less common types of tumor tissue histology.

scholarly journals Erdafitinib treatment in Brazilian patients with metastatic urothelial carcinoma (mUC): real-world evidence from an Expanded Access Program

2021 ◽  
Vol 13 ◽  
pp. 175883592110154
Author(s):  
Fernando Sabino M. Monteiro ◽  
Adriano Gonçalves e Silva ◽  
Andrea Juliana P. de S. Gomes ◽  
Carolina Dutra ◽  
Naira Oliveira Ferreira ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Objective Response ◽  
Significant Activity ◽  
Efficacy And Safety ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Real World Evidence ◽  
Metastatic Urothelial Carcinoma ◽  
Access Program

Background: Erdafitinib is the first targeted therapy approved for the treatment of patients with metastatic urothelial carcinoma (mUC). Approval was based on a phase II single-arm trial that demonstrated significant activity of erdafitinib in patients with tumors harboring FGFR2/3 alterations. In Brazil, an Expanded Access Program (EAP) provided patients with early access to erdafitinib prior to market authorization. The current report describes characteristics and outcomes of patients with mUC on erdafitinib therapy. Methods: Patients with mUC that failed first- and second-line systemic therapies were screened for FGFR2/3 alterations in primary or metastatic tumor tissues. Patients with FGFR2/3 alterations were selected to receive erdafitinib at the standard dosing schedule and were followed prospectively to evaluate the efficacy and safety outcomes. Results: From 19 April 2019, through 13 March 2020, 47 patients with mUC from 10 Brazilian centers were tested for FGFR2/3 alterations. Alterations in FGFR2/3 were found in 12 patients (25.5%) and all of them were eligible for the EAP. Four patients (33%) had partial response, while two patients (17%) had stable disease. Progressive disease, the best response, was observed in five patients (42%). At a median follow-up of 16.2 months, the median time to treatment failure (TTF) was 2.8 months. When considering only patients with objective response, the median TTF was 5.3 months. Adverse events (AEs) were reported for any grade and grade 3 or higher in 10 patients (83%) and 5 patients (42%), respectively. The most common AE was hyperphosphatemia. Conclusion: This first real-world evidence report of heavily treated patients with mUC confirms the efficacy and safety of erdafitinib in a disease setting with a lack of treatment options.

Atezolizumab (atezo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Safety analysis from an expanded access study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4532-4532
Author(s):  
Joaquim Bellmunt ◽  
Sumanta K. Pal ◽  
Hanzhe Zheng ◽  
Darren Tayama ◽  
Dannis Chang ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Clinical Activity ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Fda Approval ◽  
The Us ◽  
Metastatic Urothelial Carcinoma ◽  
Access Program ◽  
Clinical Trial Information ◽  
Efficacy Population

4532 Background: A majority of mUC pts progress on standard platinum-based chemo regimens. Atezo (anti–PD-L1) was approved in the US for mUC in the post-platinum setting. Here we report the preliminary safety results from an expanded access program conducted to grant access to atezo, prior to commercial availability, to a broader range of mUC pts than are typically eligible for Phase I-III studies. Methods: From Nov 2015-Aug 2016, this study (NCT02589717) enrolled mUC pts who progressed during or following platinum. Atezo was given 1200 mg IV q3w, and pts could be treated post RECIST v1.1 PD until lack of clinical benefit (per investigator). Safety and clinical activity were key endpoints. PD-L1 expression on immune cells (IC) was assessed with the VENTANA SP142 IHC assay on the first 73 pts prior to protocol amendment omitting this requirement. This study was ended early following FDA approval of atezo. Results: 218 pts were enrolled at 36 sites in the US, with 214 treated pts comprising the safety/efficacy population (Table). Median treatment duration was 9 wks (range 3-26), corresponding to a median of 3 doses of atezo (range 1-8). Overall, 89% of pts had an AE. Treatment-related AEs (TRAEs) occurred in 46% (any Gr) and 7% (Gr3-4) of pts; 2 treatment-related Gr 5 AEs were seen (ileus; acute respiratory failure). TRAEs ≥ 5% were fatigue, decreased appetite and anemia. TRAEs leading to dose interruption or discontinuation occurred in 11% and 6% of pts, respectively. Investigator-assessed RECIST v1.1 ORR was 15% (95% CI: 9, 23), and disease control rate (ORR + SD) was 49% (95% CI: 40, 59). Additional clinical data will be reported. Conclusions: In this expanded access study, atezo was administered to > 200 mUC pts. Overall, atezo was safe and tolerable, supporting its use in a wider platinum-based population. Clinical trial information: NCT02589717. [Table: see text]

scholarly journals Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma

JAMA Oncology ◽  
2017 ◽  
Vol 3 (9) ◽  
pp. e172411 ◽  
Author(s):  
Thomas Powles ◽  
Peter H. O'Donnell ◽  
Christophe Massard ◽  
Hendrik-Tobias Arkenau ◽  
Terence W. Friedlander ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Locally Advanced ◽  
Efficacy And Safety ◽  
Metastatic Urothelial Carcinoma

scholarly journals Efficacy and safety of rucaparib in previously treated, locally advanced or metastatic urothelial carcinoma from a phase 2, open-label trial (ATLAS)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
P. Grivas ◽  
Y. Loriot ◽  
R. Morales-Barrera ◽  
M. Y. Teo ◽  
Y. Zakharia ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Locally Advanced ◽  
Significant Activity ◽  
Efficacy And Safety ◽  
Open Label ◽  
Pathway Gene ◽  
Metastatic Urothelial Carcinoma ◽  
Previously Treated

Abstract Background ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). Methods Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. Results Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6–1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1–10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. Conclusions Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer. Trial registration This trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017–004166-10).

Cisplatin and gemcitabine administered every two weeks in patients with locally advanced or metastatic urothelial carcinoma and impaired renal function

2012 ◽  
Vol 48 (12) ◽  
pp. 1816-1821 ◽  
Author(s):  
Rafael Morales-Barrera ◽  
Joaquim Bellmunt ◽  
Cristina Suárez ◽  
Claudia Valverde ◽  
Marta Guix ◽  
...  
Keyword(s):  
Renal Function ◽  
Urothelial Carcinoma ◽  
Impaired Renal Function ◽  
Locally Advanced ◽  
Metastatic Urothelial Carcinoma
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