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Improving Cost-effectiveness of Second-line Pembrolizumab for Advanced Urothelial Carcinoma

Key findings

  • For second-line treatment of advanced urothelial carcinoma (UC), pembrolizumab was not cost-effective when tested against chemotherapy in computer models, at a willingness-to-pay threshold of $100,000/quality-adjusted life year
  • The price of pembrolizumab would need to be lowered by 15% in order to make pembrolizumab drug cost-effective in such patients
  • The estimated annual incremental cost of using the PD-L1 test strategy on a national level would be $15 million to $16.5 million per year if all eligible patients with advanced UC received pembrolizumab

Pembrolizumab is approved in the U.S. and U.K. for the treatment of locally advanced or metastatic urothelial carcinoma (UC). Studies in those countries have shown that second-line pembrolizumab for advanced UC is not cost-effective at reasonable willingness-to-pay thresholds, but neither study considered a strategy in which pembrolizumab use is limited to patients whose tumors express programmed death ligand 1 (PD-L1).

PD-L1 is expressed on the surface of UC cells and is the target of pembrolizumab and other checkpoint inhibitor immunotherapies.

Using microsimulation models, researchers from Massachusetts General Hospital including Chung Yin Kong, PhD, assistant director of the Institute for Technology Assessment, and colleagues have found that PD-L1 testing might improve the cost-effectiveness of second-line pembrolizumab in advanced UC. Their report appears in Urologic Oncology.

Computer Simulations

The researchers developed computer models to estimate the health and economic outcomes of patients with advanced UC who experience disease progression after first-line platinum-based chemotherapy. They simulated one million patients for each of three strategies:

  • All patients receive standard second-line chemotherapy, docetaxel for 50% of patients and paclitaxel for 50% (reference group)
  • All patients receive pembrolizumab
  • Patients with PD-L1–positive tumors receive pembrolizumab; others receive second-line chemotherapy

The hypothetical patients were followed from progression-free survival to progressive disease and finally death. KEYNOTE-045, the original trial of pembrolizumab in UC, was used as the source of data on PD-L1 test results, progression rates and survival rates.

Treatment strategies were evaluated through a societal lens of the U.S. healthcare system; costs considered were drug therapy and administration, PD-L1 staining, treatment of major adverse events, surveillance and supportive care. The research team calculated an incremental cost-effectiveness ratio (ICER) for each of the three strategies, using $100,000/QALY (quality-adjusted life year) as the willingness-to-pay threshold. Costs were adjusted to the 2017 U.S. dollar based on the Centers for Medicare and Medicaid Services Personal Health Care Price Index.

Cost-effectiveness Results

Limiting pembrolizumab to PD-L1–positive patients was more cost-effective than giving standard chemotherapy to all patients. The estimated average cost was $27,579 and the average quality-adjusted survival was 0.51 QALYs (estimated life expectancy 1.01 years), resulting in an ICER of $122,933/QALY.

Still, the ICER was above the prespecified $100,000/QALY willingness-to-pay threshold.

Treating all patients with pembrolizumab was less cost-effective than using PD-L1 testing. The estimated average cost was $40,573 and the average quality-adjusted survival was 0.58 QALYs (estimated life expectancy 1.16 years), resulting in an ICER of $197,383/QALY.

In sensitivity analyses, it would be necessary to lower the price of pembrolizumab by 15%, from $47.97 per milligram to $40.60 per milligram, to reduce the ICER for the PD-L1 test strategy below the $100,000/QALY threshold.

Budget Impact Analysis

In 2018, there were 4,824 patients in the U.S. with stage IV urothelial carcinoma and 1,586 of them were eligible for second-line treatment after first-line chemotherapy. They determined that the total incremental cost of treating these patients, using the PD-L1 test strategy compared with chemotherapy, would be $14.9 million in 2018 and $16.5 million by 2022.

The combination of PD-L1 testing and price reduction could move the affordability of pembrolizumab in the right direction. Research concerning additional biomarkers for patient selection, such as tumor mutational burden, may enhance the cost-benefit tradeoff for pembrolizumab.

Learn about the Institute for Technology Assessment

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