Effect of PD-L1 testing on the cost-effectiveness and budget impact of pembrolizumab for advanced urothelial carcinoma of the bladder in the United States.

Our purpose was to evaluate the effect of PD-L1 testing on the cost-effectiveness of pembrolizumab for second-line treatment of advanced urothelial carcinoma in the bladder from the U.S. societal perspective. We developed a microsimulation model to compare 3 treatment strategies: (1) treat all patients with standard-of-care chemotherapy, (2) treat all patients with pembrolizumab, and (3) treat patients with PD-L1-positive tumors at a ≥1% expression threshold with pembrolizumab, and all others with standard-of-care chemotherapy. Additionally, we performed a budget impact analysis based on the projected number of urothelial carcinoma patients eligible for second-line pembrolizumab treatment. Treating all patients with chemotherapy resulted in a mean cost of $17,232 and mean effect of 0.43 quality-adjusted life-years. The PD-L1 test strategy was the most efficient strategy, with an incremental cost-effectiveness ratio of $122,933/quality-adjusted life-year. Treating all patients with pembrolizumab resulted in an incremental cost-effectiveness ratio of $197,383/quality-adjusted life-year compared to the PD-L1 test strategy. The PD-L1 test strategy would produce an incremental budget impact of $14.9 million in the first year of use compared to chemotherapy, increasing to $16.5 million in the fifth year of use. Treating all patients with pembrolizumab would produce an incremental budget impact of $19.6 million compared to the PD-L1 test strategy in its first year of use, increasing to $20.9 million by year 5. Pembrolizumab was not cost-effective in either strategy based on a $100,000/quality-adjusted life-year willingness-to-pay threshold. Using PD-L1 testing to select for patients who may have better associated outcomes may improve the affordability of pembrolizumab.

Criss SD ，Weaver DT ，Sheehan DF ，Lee RJ ，Pandharipande PV ，Kong CY ... -  《-》

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy.

There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients. To assess the cost-effectiveness of pembrolizumab for first-line treatment of urothelial carcinoma ineligible for cisplatin-based therapy in patients with strongly PD-L1-positive tumours in Sweden. Parametric survival curves were fitted to overall survival, progression-free survival, and time on treatment data from KEYNOTE-052 to extrapolate clinical outcomes. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin plus gemcitabine and gemcitabine monotherapy. EQ-5D data from KEYNOTE-052 were used to estimate utility, while resource use and cost inputs were estimated using Swedish regional pricing lists and clinician opinion. The model reported costs, life years, and quality-adjusted life years (QALYs), and results were tested using deterministic and probabilistic sensitivity analysis. We estimated that pembrolizumab would improve survival by 2.11 and 2.16 years and increase QALYs by 1.71 and 1.75 compared to carboplatin plus gemcitabine and gemcitabine monotherapy, respectively. Pembrolizumab was associated with a cost increase of €90520 versus carboplatin plus gemcitabine and €95055 versus gemcitabine, with corresponding incremental cost-effectiveness ratios of €53055/QALY and €54415/QALY. At a willingness-to-pay threshold of €100000/QALY, pembrolizumab is a cost-effective treatment versus carboplatin plus gemcitabine and versus gemcitabine. This is the first analysis to show that pembrolizumab is a cost-effective option for first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in Sweden.

Patterson K ，Prabhu V ，Xu R ，Li H ，Meng Y ，Zarabi N ，Zhong Y ，Batteson R ，Pellissier J ，Keefe S ，Grivas P ，de Wit R ... -  《European Urology Oncology》

Cost-effectiveness of Pembrolizumab as Second-line Therapy for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma in Sweden.

Urothelial carcinoma (UC) is the most common subtype of bladder cancer. The randomized phase 3 KEYNOTE-045 trial showed that pembrolizumab, used as second-line therapy significantly prolonged overall survival with fewer treatment-related adverse events than chemotherapy for advanced UC. Pembrolizumab has been approved by the European Medicines Agency for the treatment of locally advanced or metastatic UC in adults who have received platinum-containing chemotherapy. Many European countries use cost-effectiveness analysis to inform reimbursement decisions. To assess the cost-effectiveness of pembrolizumab as second-line therapy for the treatment of advanced UC from a Swedish health care perspective. We developed a partitioned-survival model to assess the costs and effectiveness of pembrolizumab compared with vinflunine (base case), paclitaxel, or docetaxel monotherapy in patients with advanced UC over a 15-yr time horizon. We obtained Kaplan-Meier estimates for survival endpoints, adverse events, and utility data from KEYNOTE-045. We performed parametric extrapolations to estimate overall and progression-free survival beyond the clinical trial period. Swedish costs and utility weights were used to estimate total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We performed deterministic and probabilistic sensitivity analyses to assess the robustness of the model results. In the base-case analysis, pembrolizumab resulted in a mean survival gain of 1.66 years (1.38 QALYs) at an incremental cost of €69852 and an ICER of €50529/QALY gained versus vinflunine monotherapy. ICERs for other chemotherapies were €81356/QALY for pembrolizumab versus paclitaxel or docetaxel monotherapy, and €71924/QALY for pembrolizumab versus paclitaxel, docetaxel, or vinflunine monotherapy. Long-term follow-up from KEYNOTE-045 and real-world data are needed to validate the extrapolations. The results indicate that pembrolizumab improves survival, increases QALYs, and is cost-effective as second-line therapy at a willingness-to-pay threshold of €100000/QALY for the treatment of advanced UC. To date, pembrolizumab is the only treatment associated with a significant overall survival benefit compared with chemotherapy in a randomized controlled trial as second-line therapy for advanced urothelial carcinoma. Our trial-based cost-effectiveness analysis suggests that pembrolizumab is a cost-effective option over chemotherapy in patients with advanced urothelial carcinoma after platinum-based therapy in Sweden.

Srivastava T ，Prabhu VS ，Li H ，Xu R ，Zarabi N ，Zhong Y ，Pellissier JM ，Perini RF ，de Wit R ，Mamtani R ... -  《European Urology Oncology》

Cost-effectiveness of Pembrolizumab in Second-line Advanced Bladder Cancer.

Immune-modulating drugs have recently been introduced to the second-line setting of advanced bladder cancer. Pembrolizumab increases overall survival and is associated with less toxicity compared with chemotherapy in this setting based on the Keynote 045 study. The high cost of immunotherapy necessitates an assessment of its value by considering both efficacy and cost. To estimate the cost-effectiveness of pembrolizumab for the second-line treatment of advanced bladder cancer from the perspective of payers in multiple countries. We developed a Markov model to compare the cost and effectiveness of pembrolizumab with those of chemotherapy in the second-line treatment of advanced bladder cancer based on the Keynote 045 study. Drug costs were acquired for the United States (US), United Kingdom (UK), Canada, and Australia. All costs were converted from local currency to US dollars at the exchange rates in September 2017. Health outcomes were measured in quality-adjusted life-years (QALYs). Pembrolizumab generated a gain of 0.36-0.37 QALYs compared with chemotherapy. Our analysis established the following incremental cost-effectiveness ratios (ICERs) for pembrolizumab versus chemotherapy in second-line advanced bladder cancer treatment: US $122 557/QALY; UK $91 995/QALY; Canada $90 099/QALY; and Australia $99 966/QALY. The willingness-to-pay (WTP) thresholds per QALY are considered to be around 100 000-150 000 US dollars for the US, 20 000-50 000 pounds for the UK (US$25 000-65 000), 20 000-100 000 CAD for Canada (US$16 000-80 000), and 40 000-75 000 AUD for Australia (US$32 000-60 000). Cost-effectiveness and WTP thresholds vary between countries. Compared with the other countries examined, US drug prices were found to be the highest, leading to the highest ICER. With standard WTP thresholds, pembrolizumab may be considered cost-effective in the US but not in the other countries examined. This article assessed the cost-effectiveness of pembrolizumab for the treatment of patients with metastatic bladder cancer who had previously failed one treatment regimen. It would cost $122 557 in the United States, $91 995 in the United Kingdom, $90 099 in Canada, and $99 966 in Australia to gain one quality-adjusted life-year with pembrolizumab versus chemotherapy in these patients, which may be considered cost-effective only in the United States because of the differences in willingness-to-pay thresholds.

Sarfaty M ，Hall PS ，Chan KKW ，Virik K ，Leshno M ，Gordon N ，Moore A ，Neiman V ，Rosenbaum E ，Goldstein DA ... -  《-》

Cost-Effectiveness of Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma in the United States.

The JAVELIN Bladder 100 trial showed that maintenance avelumab therapy after chemotherapy improved the survival of patients with advanced or metastatic urothelial carcinoma. We analyzed the cost-effectiveness of maintenance therapy with avelumab plus best supportive care (BSC) in patients with advanced or metastatic urothelial carcinoma after receiving first-line platinum-based chemotherapy from the US payer perspective. A Markov model was used to analyze the economic outcomes of maintenance avelumab plus BSC (avelumab strategy) in the treatment of urothelial carcinoma. The clinical data were derived from the JAVELIN Bladder 100 trial. All cost information was obtained from Medicare and published literature. The total cost, total life years (LYs), total quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net health benefit (INHB) were calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed. Our results showed that avelumab strategy versus BSC strategy cost US $176,352 and $238,661 and yielded an additional 0.465 and 1.007 QALY in all patients with unknown programmed-death ligand 1 (PD-L1) status and the PD-L1-positive subpopulation, respectively, which led to an ICER of $102,365/QALY and $106,253/QALY gained. In all patients with unknown PD-L1 status, maintenance avelumab plus BSC therapy guiding by PD-L1 expression testing (PD-L1-guided strategy) compared with the avelumab strategy and BSC strategy resulted in ICER of $105,360/QALY and $122,653/QALY, respectively. The probabilities of the avelumab strategy and the PD-L1-guided strategy being cost-effective in the simultaneous competition of the three strategies were 38.49% and 48.82%. In patients with PD-L1-positive status, the avelumab strategy had an 87.51% probability of cost-effectiveness. The most influential parameter for the model was the cost of avelumab and pembrolizumab. This analysis demonstrated that maintenance therapy with avelumab plus BSC may be a cost-effective option for patients with advanced or metastatic urothelial carcinoma at a willingness-to-pay (WTP) threshold of $150,000/QALY, especially for patients with PD-L1-positive status.

Peng Y ，She Z ，Peng L ，Liu Q ，Yi L ，Luo X ，Li S ，Wang L ，Qin S ，Wan X ，Tan C ... -  《-》