Treatment patterns and overall survival in metastatic urothelial carcinoma in a real-world, US setting

Simeone, Jason C; Nordstrom, Beth L.; Patel, Ketan M.; Mann, Helen; Klein, Alyssa; Horne, Laura

doi:10.1016/j.canep.2019.03.013

Cited by 32 publications

(38 citation statements)

References 20 publications

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“…In the new scenario, 3.0% of the IO market was assumed to come from avelumab across all 3 years, with uptake in the total market mix of all 2L treatments as 1.7% in year 1, 1.2% in year 2 and 1.0% in year 3. The CT was considered to be a “basket” of agents consisting of carboplatin (45.9%), gemcitabine (25.6%), docetaxel (12.4%), paclitaxel (45.1%), and pemetrexed (16.9%), based on the frequency of use observed in a real-world observational study 10. The sum of CT use was greater than 100% due to the combination of CT agents.…”

Section: Methodsmentioning

confidence: 99%

“…Dosages for CT were based on average body surface area (1.89 m2) observed in patients in the mUC cohort in the Javelin Solid Tumor trial (NCT01772004), with the exception of carboplatin treatment, which was based on the area under the plasma drug concentration–time curve 13. The cost of CT regimens was taken as a weighted average of the “basket” of CT as described in a real-world study of treatment patterns in mUC patients in the US 10. Median TTF was extracted for 2L CT and IO agents from a real-world evidence study using the US Oncology Network electronic health records database and used as a proxy for treatment duration 30.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, 21% of 2L patients were assumed to progress to 3L therapy based on real-world US data 30. The 3L CT mix (carboplatin 19%, gemcitabine 19%, docetaxel 19%, paclitaxel 20% and pemetrexed 52%) was based on US real-world data 10. This sum is greater than 100% due to combination therapy.…”

Section: Methodsmentioning

confidence: 99%

“…Patients are deemed ineligible for cisplatin based on one of the following criteria: Eastern Cooperative Oncology Group performance status ≥2, creatinine clearance (CrCl) <60 mL/min, Common Terminology Criteria for Adverse Events grade ≥2 hearing loss, or ≥2 neuropathy, and these criteria are reflected in real-world US treatment patterns where cisplatin-treated metastatic bladder cancer patients were found to be younger and had fewer comorbidities than non-cisplatin-treated patients 8,9. In the US, the most commonly used CT agents in 2L are gemcitabine, carboplatin, and paclitaxel 10. One phase III study, which assessed locally advanced or mUC patients who had progressed on platinum-based treatment and were subsequently treated with CT, found an objective response rate of 22%, a median overall survival (OS) of 10.6 months (95% CI, 8.4–12.2), and a grade III-IV adverse event (AE) in 43% of the patients 11.…”

Section: Introductionmentioning

confidence: 99%

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<p>Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives</p>

Kongnakorn¹,

Bharmal

Kearney

et al. 2019

CEOR

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ObjectiveTo estimate the budget impact of introducing avelumab as a second-line (2L) treatment option for patients with locally advanced or metastatic urothelial cancer (mUC) from the perspective of a US third-party payer (commercial and Medicare).MethodsA budget impact model (BIM) with a three-year time horizon was developed for avelumab. Efficacy and safety data were sourced from published literature and US package inserts. The analysis was conducted in collaboration with a specialist oncologist who validated clinical assumptions. Costs were based on the number of eligible patients, time-to-treatment failure, overall survival, adverse events (AEs), and projected market shares of various treatments.ResultsIn a hypothetical commercial health plan of 30,000,000 members, 884 patients were estimated to be eligible for 2L treatment over a three-year time period. Without avelumab, the total cost for treating patients with mUC was estimated to be US$70,268,035. The introduction of avelumab increased total costs by $73,438 (0.10% increase). In a hypothetical Medicare health plan of 30,000,000 beneficiaries, a total of 4,705 patients were estimated to be eligible for 2L treatment. Without avelumab, the total cost for treating patients with mUC was estimated to be $292,923,098 from a Medicare perspective; however, with avelumab, there was an increase of $719,324 (0.25% increase) in total costs. Results of the sensitivity analyses demonstrated a cost-neutral impact across all tested scenarios from both perspectives.ConclusionThe BIM estimated that avelumab would have a cost-neutral impact within a US commercial and a Medicare health plan. Overall, avelumab can be an affordable and valuable treatment option for patients with locally advanced or mUC in the 2L setting. These findings demonstrate a consistently favorable budget impact in both populations. Further studies should be conducted to more comprehensively assess the clinical and economic implications of adding avelumab to the treatment armamentarium of 2L mUC.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

<p>Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives</p>

Kongnakorn¹,

Bharmal

Kearney

et al. 2019

CEOR

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“…Surgery, chemotherapy, radiotherapy, molecular-targeted therapy, and immunotherapy are the current standard treatments. However, patients with advanced lung cancer have 10-15% overall 5-year survival rates, an median overall survival (OS) of about 11.1 months, and a post-recurrence survival rate (PRS) of 13% (hazard ratio (HR) = 0.78) [2][3][4]. Even with second-line drug treatment, such as nivolumab, progression-free survival (PFS) is about 2.3-3.5 months [5].…”

Section: Introductionmentioning

confidence: 99%

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

Chang

Hsiao

et al. 2019

Cancers

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Dysregulation of forkhead box D1 (FOXD1) is known to promote tumor progression; however, its molecular mechanism of action is unclear. Based on microarray analysis, we identified galectin-3/LGALS3 (Gal-3) as a potential downstream target of FOXD1, as FOXD1 transactivated Gal-3 by interacting with the Gal-3 promoter to upregulate Gal-3 in FOXD1-overexpressing CL1-0 lung cancer cells. Ectopic expression of FOXD1 increased the expression of Gal-3 and the growth and motility of lung cancer cells, whereas depletion of Gal-3 attenuated FOXD1-mediated tumorigenesis. ERK1/2 interacted with FOXD1 in the cytosol and translocated FOXD1 into the nucleus to activate Gal-3. Gal-3 in turn upregulated FOXD1 via the transcription factor proto-oncogene 1 (ETS-1) to transactivate FOXD1. The increase in ETS-1/FOXD1 expression by Gal-3 was through Gal-3-mediated integrin-β1 (ITGβ1) signaling. The overexpression of both FOXD1 and Gal-3 form a positive regulatory loop to promote lung cancer aggressiveness. Moreover, both FOXD1 and Gal-3 were positively correlated in human lung cancer tissues. Our findings demonstrated that FOXD1 and Gal-3 form a positive feedback loop in lung cancer, and interference of this loop may serve as an effective therapeutic target for the treatment of lung cancers, particularly those related to dysregulation of Gal-3.

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Treatment Patterns and Attrition With Lines of Therapy for Advanced Urothelial Carcinoma in the US

Mathew Thomas,

Jo,

Tripathi

et al. 2024

JAMA Netw Open

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ImportanceThe treatment paradigm for advanced urothelial carcinoma (aUC) has undergone substantial transformation due to the introduction of effective, novel therapeutic agents. However, outcomes remain poor, and little is known about current treatment approaches and attrition rates for patients with aUC.ObjectivesTo delineate evolving treatment patterns and attrition rates in patients with aUC using a US-based patient-level sample.Design, Setting, and ParticipantsThis retrospective cohort study used patient-level data from the nationwide deidentified electronic health record database Flatiron Health, originating from approximately 280 oncology clinics across the US. Patients included in the analysis received treatment for metastatic or local aUC at a participating site from January 1, 2011, to January 31, 2023. Patients receiving treatment for 2 or more different types of cancer or participating in clinical trials were excluded from the analysis.Main Outcomes and MeasuresFrequencies and percentages were used to summarize the (1) treatment received in each line (cisplatin-based regimens, carboplatin-based regimens, programmed cell death 1 and/or programmed cell death ligand 1 [PD-1/PD-L1] inhibitors, single-agent nonplatinum chemotherapy, enfortumab vedotin, erdafitinib, sacituzumab govitecan, or others) and (2) attrition of patients with each line of therapy, defined as the percentage of patients not progressing to the next line.ResultsOf the 12 157 patients within the dataset, 7260 met the eligibility criteria and were included in the analysis (5364 [73.9%] men; median age at the start of first-line treatment, 73 [IQR, 66-80] years). All patients commenced first-line treatment; of these, only 2714 (37.4%) progressed to receive second-line treatment, and 857 (11.8%) advanced to third-line treatment. The primary regimens used as first-line treatment contained carboplatin (2241 [30.9%]), followed by PD-1/PD-L1 inhibitors (2174 [29.9%]). The PD-1/PD-L1 inhibitors emerged as the predominant choice in the second- and third-line (1412 of 2714 [52.0%] and 258 of 857 [30.1%], respectively) treatments. From 2019 onward, novel therapeutic agents were increasingly used in second- and third-line treatments, including enfortumab vedotin (219 of 2714 [8.1%] and 159 of 857 [18.6%], respectively), erdafitinib (39 of 2714 [1.4%] and 28 of 857 [3.3%], respectively), and sacituzumab govitecan (14 of 2714 [0.5%] and 34 of 857 [4.0%], respectively).Conclusions and RelevanceThe findings of this cohort study suggest that approximately two-thirds of patients with aUC did not receive second-line treatment. Most first-line treatments do not include cisplatin-based regimens and instead incorporate carboplatin- or PD-1/PD-L1 inhibitor–based therapies. These data warrant the provision of more effective and tolerable first-line treatments for patients with aUC.

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Treatment patterns and overall survival in metastatic urothelial carcinoma in a real-world, US setting

Cited by 32 publications

References 20 publications

<p>Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives</p>

<p>Budget Impact Of Including Avelumab As A Second-Line Treatment For Locally Advanced Or Metastatic Urothelial Cancer In The United States: Commercial And Medicare Payer Perspectives</p>

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

Treatment Patterns and Attrition With Lines of Therapy for Advanced Urothelial Carcinoma in the US

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