PCN185 - COST-EFFECTIVENESS OF NIVOLUMAB IN SECOND-LINE TREATMENT OF LOCALLY ADVANCED UNRESECTABLE OR METASTATIC UROTHELIAL CARCINOMA IN ADULTS AFTER FAILURE OF PRIOR PLATINUM-CONTAINING THERAPY IN GREECE

Purpose This trial assessed the efficacy and safety of docetaxel monotherapy or docetaxel in combination with ramucirumab (vascular endothelial growth factor receptor 2 antibody) or icrucumab (vascular endothelial growth factor receptor 1 antibody) after progression during or within 12 months of platinum-based regimens for patients with locally advanced or metastatic urothelial carcinoma. Patients and Methods Patients were randomly assigned (1:1:1) to receive docetaxel 75 mg/m2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of a 3-week cycle (arm C). Treatment continued until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Results A total of 140 patients were randomly assigned and treated in arms A (n = 45), B (n = 46), or C (n = 49). PFS was significantly longer in arm B compared with arm A (median, 5.4 months; 95% CI, 3.1 to 6.9 months v 2.8 months; 95% CI, 1.9 to 3.6 months; stratified hazard ratio, 0.389; 95% CI, 0.235 to 0.643; P = .0002). Arm C did not experience improved PFS compared with arm A (1.6 months; 95% CI, 1.4 to 2.9; stratified hazard ratio, 0.863; 95% CI, 0.550 to 1.357; P = .5053). The most common grade 3 or worse adverse events (arms A, B, and C) were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively). Conclusion The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.

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A cost-utility analysis of atezolizumab in the second-line treatment of metastatic urothelial carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6639 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6639-6639

Author(s):

Ambika Parmar ◽

Marina Richardson ◽

Beate Sander ◽

Susanna Y. Cheng ◽

Kelvin K. Chan

Keyword(s):

Cost Effectiveness ◽

Urothelial Carcinoma ◽

Cost Utility ◽

Cost Utility Analysis ◽

Line Treatment ◽

Second Line ◽

Utility Analysis ◽

Lifetime Horizon ◽

Metastatic Urothelial Carcinoma

6639 Background: Despite early promising results, IMvigor211 failed to demonstrate an overall survival benefit for atezolizumab, compared to chemotherapy, in the second-line treatment of metastatic urothelial carcinoma. However, given improvements in adverse events (AE) and quality of life with atezolizumab, there may still be investment value. We conducted a cost-utility analysis (CUA) of atezolizumab compared to chemotherapy from a public-payer healthcare perspective. Methods: We developed a partitioned survival model to evaluate atezolizumab versus chemotherapy (i.e. docetaxel, paclitaxel or vinflunine). IMvigor211 informed rates of treatment receipt (initial and subsequent), AE, effectiveness and utility estimates. Cost for treatment, AE and death were based on published literature (adjusted to 2018 Canadian dollars). Per health state, cost of treatment (initial and subsequent) and AE were incorporated. Outcomes included quality-adjusted life-years (QALY), cost per treatment, and incremental cost-effectiveness ratio (ICER). QALY and cost were discounted at 1.5% (Canadian guidelines). Parameter uncertainty was assessed through one-way and scenario analyses. Time horizons of 2 (within trial) and 5 years (extrapolated lifetime) were evaluated. Results: QALY of atezolizumab and chemotherapy over 2 years (lifetime) were 0.65 (0.93) and 0.58 (0.64), respectively. Cost of atezolizumab and chemotherapy over 2 years (lifetime) was $77,614.64, ($92,484.34), and $62,212.35 ($67,606.65), respectively. ICER over 2 years and lifetime was $220,032.71/QALY and $85,785.14/QALY. Scenario analysis from a North American perspective with only taxane chemotherapy with and without third line immunotherapy (IO) revealed an ICER of $80,144.90/QALY, $125,332.76/QALY over a lifetime horizon, respectively. Conclusions: The difference in ICER dependent on time horizon, driven by extrapolated survival benefits, highlights the importance of long-term follow-up to examine whether early evidence for durable response translates into long-term survival and improvements in cost-effectiveness. Thus, CUA of IO require careful interpretation and warrant dynamic assessment as new data becomes available.

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Adverse events of the second-line treatment for patients with locally advanced or metastatic urothelial carcinoma of the bladder: network meta-analysis

Immunotherapy ◽

10.2217/imt-2020-0305 ◽

2021 ◽

Author(s):

Ekaterina Laukhtina ◽

Keiichiro Mori ◽

Hadi Mostafaei ◽

Axel S Merseburger ◽

Peter Nyirady ◽

...

Keyword(s):

Adverse Events ◽

Urothelial Carcinoma ◽

Meta Analysis ◽

Locally Advanced ◽

Combination Regimen ◽

Line Treatment ◽

Second Line ◽

Eligibility Criteria ◽

Metastatic Urothelial Carcinoma ◽

Carcinoma Of The Bladder

Aim: We aimed to compare the mortality rates related to adverse events (AEs) and discontinuation of treatment due to toxicity as well as all AEs of currently used regimens of second-line treatment strategies for advanced or metastatic urothelial carcinoma of the bladder. Methods: The MEDLINE and EMBASE databases were searched for articles according to the PRISMA extension statement for network meta-analysis. Results: Five trials comprising 2205 patients met our eligibility criteria. It is highly likely that immunotherapy, as single regimen, has the lowest rates of motor and sensory neuropathies, constipation, abdominal pain, alopecia, decreased appetite, vomiting and febrile neutropenia. Immunotherapy, in combination regimen, has the lowest rates of anemia and fatigue. Conclusion: Immunotherapy, especially as single regimen, demonstrated the highest favorable tolerability to most AEs.

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Cost-effectiveness of pembrolizumab as second-line therapy for the treatment of locally advanced or metastatic urothelial carcinoma in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16010 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16010-e16010

Author(s):

Yichen Zhong ◽

Yizhen Lai ◽

Haojie Li ◽

Rachael Batteson ◽

Yang Meng ◽

...

Keyword(s):

Cost Effectiveness ◽

Incremental Cost ◽

Urothelial Carcinoma ◽

Time Horizon ◽

Locally Advanced ◽

Cost Effective ◽

The United States ◽

Second Line ◽

Life Years ◽

Metastatic Urothelial Carcinoma

e16010 Background: Pembrolizumab is approved by the US Food and Drug Administration for the treatment of locally advanced or metastatic urothelial carcinoma (mUC) following platinum-based chemotherapy, based on results from KEYNOTE-045. In this randomized phase 3 trial, pembrolizumab significantly prolonged overall survival (OS) vs. chemotherapy in mUC patients (cut-off: Oct 26, 2017). The current analysis evaluates the cost-effectiveness of pembrolizumab vs. standard-of-care chemotherapy (docetaxel or paclitaxel) as second-line (2L) treatment for mUC, from a US payer perspective. Methods: We developed a partitioned-survival model to measure the costs and effectiveness over a 20-year time horizon to capture long-term costs and benefits from the treatments. Clinical efficacy, time on treatment, safety and utility data were derived from KEYNOTE-045. OS and progression-free survival were extrapolated beyond the trial period using piecewise models, i.e., Kaplan-Meier data followed by parametric function. Costs (in 2018 $US) for drug acquisition/administration, disease monitoring, adverse events management and terminal care were included. Costs and outcomes were discounted at 3% per year. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the results. Results: Pembrolizumab resulted in a mean gain of 1.33 life years (LYs) and 1.14 quality-adjusted life-years (QALYs) at an incremental cost of $103,861 vs. chemotherapy. The incremental cost-effectiveness ratios were $91,103/QALY and $78,254/LY. Key drivers of cost-effectiveness were extrapolation methods for OS data, time horizon and utility values. Pembrolizumab had a 72% or 100% probability of being cost-effective vs. chemotherapy at a $100,000 or $150,000 willingness-to-pay threshold, respectively. Conclusions: Pembrolizumab appears to be cost-effective vs. docetaxel or paclitaxel monotherapy as 2L mUC therapy when accounting for durable survival seen in a subset of patients receiving pembrolizumab. The model was established based on robust estimates, with key clinical endpoints directly drawn or derived from patient level data in KEYNOTE-045.

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Paclitaxel, ifosfamide, and nedaplatin as second-line treatment for patients with metastatic urothelial carcinoma: A phase II study of the SUOC group

Cancer Science ◽

10.1111/j.1349-7006.2011.01909.x ◽

2011 ◽

Vol 102 (6) ◽

pp. 1171-1175 ◽

Cited By ~ 20

Author(s):

Hiroshi Kitamura ◽

Keisuke Taguchi ◽

Yasuharu Kunishima ◽

Masahiro Yanase ◽

Atsushi Takahashi ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Phase Ii ◽

Phase Ii Study ◽

Line Treatment ◽

Second Line ◽

Metastatic Urothelial Carcinoma

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Gemcitabine and ifosfamide as a second-line treatment for cisplatin-refractory metastatic urothelial carcinoma: a phase II study

Anti-Cancer Drugs ◽

10.1097/cad.0b013e3280126603 ◽

2007 ◽

Vol 18 (4) ◽

pp. 487-491 ◽

Cited By ~ 28

Author(s):

Chia-Chi Lin ◽

Chih-Hung Hsu ◽

Chao-Yuan Huang ◽

Hsiao-Yi Keng ◽

Yu-Chieh Tsai ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Phase Ii ◽

Phase Ii Study ◽

Line Treatment ◽

Second Line ◽

Metastatic Urothelial Carcinoma

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Faculty of 1000 evaluation for Nanoparticle albumin-bound paclitaxel for second-line treatment of metastatic urothelial carcinoma: a single group, multicentre, phase 2 study.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.718013350.793478370 ◽

2013 ◽

Author(s):

Kenneth Pienta

Keyword(s):

Urothelial Carcinoma ◽

Line Treatment ◽

Second Line ◽

Phase 2 ◽

Single Group ◽

Multicentre Phase ◽

Phase 2 Study ◽

Metastatic Urothelial Carcinoma

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Clinical Outcomes of Three or More Courses of First-line Chemotherapy for Metastatic Urothelial Carcinoma

Cancer Diagnosis & Prognosis ◽

10.21873/cdp.10061 ◽

2021 ◽

Vol 1 (5) ◽

pp. 459-461

Author(s):

SHOHEI KAWAGUCHI ◽

KOUJI IZUMI ◽

RENATO NAITO ◽

SUGURU KADOMOTO ◽

HIROAKI IWAMOTO ◽

...

Keyword(s):

Drug Therapy ◽

Urothelial Carcinoma ◽

Focal Therapy ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Metastatic Urothelial Carcinoma ◽

Line Drug ◽

Line Chemotherapy ◽

First Line Treatment

Background/Aim: The current standard of care for first-line treatment of locally advanced or metastatic urothelial carcinoma (UC) is platinum-based combination chemotherapy. Recently, immune checkpoint inhibitors have been reported to be effective for UC. Knowing whether immunotherapy or chemotherapy is suitable as first-line treatment is beneficial for patients. A retrospective study was conducted on the clinical outcomes of Japanese patients who received three or more courses of first-line chemotherapy for metastatic UC to assess the outcome of conventional treatments in real clinical situation. Patients and Methods: Patients who received first-line chemotherapy between August 2009 and December 2019 were included. Progression-free survival (PFS) and overall survival (OS) were assessed. Results: The median PFS and OS were 7.1 and 27.1 months, respectively, for patients with no disease progression at the end of three courses. Of 28 patients, 25 (89.3%) received second-line drug therapy and 10 (35.7%) received focal therapy for disease control. Patients with focal therapy had significantly longer OS than those without focal therapy (p=0.019, log-rank test). Conclusion: OS of metastatic UC at our Institution is relatively long, suggesting that aggressive second-line drug therapy and focal therapy may have contributed to such result.

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