Urologic Oncology: Seminars and Original Investigations
Clinical-Bladder cancerEffect of PD-L1 testing on the cost-effectiveness and budget impact of pembrolizumab for advanced urothelial carcinoma of the bladder in the United States
Graphical abstract
Introduction
Bladder cancer is the sixth most common type of cancer in the United States and is associated with poor late-stage survival [1]. Urothelial carcinoma is the predominant histologic type of bladder cancer [2], [3], making it a primary target for new immunotherapy treatments. Five immunotherapy treatments have been approved for the treatment of urothelial carcinoma by the U.S. Food and Drug Administration (FDA), each of them acting as checkpoint inhibitors to activate the immune system against cancer cells. Estimates from the biopharmaceutical industry project that total annual revenues from immunotherapy could reach up to $20 to $30 billion in the coming decade [4]. In an environment with strong financial incentives for pharmaceutical companies to increase drug prices, formal cost-effectiveness analysis can provide important context for public policymakers and prescribing physicians on the underlying value of such therapies.
The FDA approved pembrolizumab (Keytruda, Merck Sharp & Dohme Corp.) in 2017 to treat locally advanced or metastatic urothelial carcinoma in patients whose cancer progressed during or after first-line chemotherapy [5]. Pembrolizumab is a programmed cell death protein 1 (PD-1) immune-checkpoint–inhibitor antibody that obstructs PD-1–mediated signaling and, thus, restores antitumor T-cell activation [6]. In a randomized, open-label, phase 3 international study (KEYNOTE-045, NCT02256436), overall survival with pembrolizumab was greater than that with the comparator regimen: docetaxel, paclitaxel, or vinflunine (10.3 months vs. 7.4 months, respectively) [6]. Patients receiving pembrolizumab also experienced a lower adverse event rate [6]. Patients whose tumors expressed higher PD-1 ligand (PD-L1) expression had improved survival when on pembrolizumab compared to chemotherapy [6].
Prior analysis by the U.K.’s National Institute for Health and Care Excellence (NICE) concluded that pembrolizumab should not be recommended for treating advanced urothelial carcinoma in the second line because it was not cost-effective at a willingness-to-pay (WTP) threshold of £50,000/quality-adjusted life-year (QALY) [7]. A recently published study by Sarfaty et al. examined the cost-effectiveness of pembrolizumab vs. chemotherapy for second-line treatment of advanced bladder cancer in the U.S.A., U.K., Canada, and Australia, concluding that it was only cost-effective in the United States at a WTP threshold of $150,000/QALY [8]. Neither of these studies considered a strategy in which pembrolizumab treatment was dependent on PD-L1 expression, nor did they assess the potential budget impact of adopting pembrolizumab-based treatment strategies. Based on these conclusions and in light of the growing market for immuno-oncology therapies, an analysis of the cost per QALY tradeoff of using pembrolizumab, with or without prior PD-L1 testing, in treating advanced urothelial carcinoma in the United States is warranted.
Section snippets
Simulation model
We developed a microsimulation model to estimate health and economic outcomes of patients presenting with advanced urothelial carcinoma in the bladder who experienced disease progression after first-line platinum-based chemotherapy. We compared 3 strategies in our base case analysis: (1) treat all patients with standard-of-care second-line chemotherapy (50% receiving docetaxel and 50% receiving paclitaxel), (2) treat all patients with pembrolizumab, and (3) treat patients with PD-L1-positive
Results
We found that patients in the standard-of-care chemotherapy strategy accumulated a mean cost of $17,232 and mean quality-adjusted survival of 0.43 QALYs, with an estimated life expectancy of 0.83 years. The PD-L1 test strategy was the most efficient in comparison to standard-of-care chemotherapy, with an estimated mean cost of $27,579 and mean quality-adjusted survival of 0.51 QALYs (estimated life expectancy = 1.01 years), resulting in an ICER of $122,933/QALY (Table 2). Treating all patients
Discussion
Pembrolizumab has been approved for treatment of a number of different cancers (i.e., urothelial carcinoma, nonsmall cell lung cancer, Hodgkin's lymphoma, head and neck cancer, melanoma, and gastric cancer) and its effectiveness in advanced stage cancers has been substantiated by numerous clinical trials [6], [27], [28], [29], [30], [31]. Using the results of the KEYNOTE-045 clinical trial and other literature sources, we found that pembrolizumab was not cost-effective in either of the
Conclusions
We found that pembrolizumab was not a cost-effective option for the treatment of advanced urothelial carcinoma of the bladder for either of the strategies tested at a WTP threshold of $100,000/QALY. In sensitivity analyses, we determined that significant price reductions would be required to make treating advanced urothelial carcinoma with pembrolizumab an acceptable strategy from a health system perspective. As other immunotherapies approved for treatment of advanced urothelial carcinoma
Funding
None declared.
Disclosure
The authors have declared no conflicts of interest.
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