Cost-effectiveness of Pembrolizumab versus Carboplatin-based Chemotherapy as First-line Treatment of PD-L1–positive Locally Advanced or Metastatic Urothelial Carcinoma Ineligible for Cisplatin-based Therapy in the United States

Abstract

A partitioned survival cost-effectiveness model informed by the final analyses from KEYNOTE-052 predicted long-term health and cost outcomes for cisplatin-ineligible patients with urothelial cancer with programmed death-ligand 1-positive tumors receiving either pembrolizumab or carboplatin plus gemcitabine. Over 20 years, treatment with pembrolizumab resulted in a mean gain of 2.58 life years and was shown to be cost-effective over carboplatin plus gemcitabine. Introduction: Pembrolizumab has been approved in the United States (US) for the first-line treatment of patients with advanced or metastatic urothelial carcinoma, who are ineligible for cisplatin-containing chemotherapy and with tumors expressing programmed death-ligand 1 (PD-L1) (Combined Positive Score ! 10), or ineligible for any platinumcontaining chemotherapy regardless of PD-L1 status. Long-term KEYNOTE-052 data continue to demonstrate pembrolizumab's meaningful, durable, and well-tolerated antitumor activity. This study evaluates the costeffectiveness of pembrolizumab versus carboplatin plus gemcitabine as first-line treatment for cisplatin-ineligible patients who have PD-L1epositive tumors from a US third-party healthcare payer's perspective. Patients and Methods: A partitioned survival model containing 3 health states (progression-free, progressed, and death) was developed. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin-based chemotherapy. Overall survival, progression-free survival, time on treatment, adverse events, and utilities were modeled using the final analyses of the KEYNOTE-052 trial and 4 studies for carboplatin plus gemcitabine. Cost data were estimated using US standard sources and real-world data. Deterministic, probabilistic, and scenario analyses were conducted to assess the robustness of the results. Results: Over 20 years, pembrolizumab resulted in a mean gain of 2.58 life-years, 2.01 quality-adjusted life-years, and additional costs of $158,561, leading to an incremental cost-effectiveness ratio of $78,925/qualityadjusted life-year compared with carboplatin plus gemcitabine. Conclusion: This study suggests that pembrolizumab is cost-effective compared with carboplatin plus gemcitabine as a first-line therapy for patients with advanced or metastatic urothelial carcinoma who are PD-L1epositive.

Cost-Effectiveness of Avelumab Maintenance Therapy Plus Best Supportive Care vs. Best Supportive Care Alone for Advanced or Metastatic Urothelial Carcinoma

“…A recent study based on the JAVELIN Bladder 100 Clinical Trial demonstrate that avelumab maintenance therapy was cost-effective both in the overall population and PD-L1–positive population in the US, which was similar to our results ( 28 ). Pembrolizumab, another ICIs, was demonstrated as a cost-effective first-line treatment for patients with mUC whose tumors strongly expressed PD-L1 in Sweden and the US at the WTP threshold of £100,000 and $150,000 per QALY, respectively ( 20 , 21 ). Although pembrolizumab shows great efficacy for patients with UC, recently the National Institute for Health and Care Excellence (NICE) decided to reject coverage of pembrolizumab for platinum-refractory UC due to its failure to meet their threshold of £50,000/QALY in the UK, which was also a good illustration for the growing importance of cost-effectiveness analysis in expensive treatments ( 29 ).…”

Cost-Effectiveness of Immune Checkpoint Inhibitors in Urothelial Carcinoma—A Review

“…Hale et al evaluated first-line pembrolizumab vs. gemcitabine/carboplatin (GCa) in cisplatin-ineligible patients whose tumors expressed PD-L1 with a CPS ≥10% [ 15 ]. A partitioned survival model with the similar three health states was created using the KEYNOTE-052 trial as a template for PFS and OS estimates [ 9 ].…”

Atezolizumab plus platinum-based chemotherapy as first-line therapy for metastatic urothelial cancer: A cost-effectiveness analysis

“…We noted that similar economic studies on pembrolizumab for urothelial cancer showed an improvement in survival benefit significantly. Hale et al (2021 ) concluded that pembrolizumab was a cost-effective alternative to chemotherapy based on a US third-party healthcare payer’s perspective, with a significant QALY benefit (2.91 QALYs in the pembrolizumab group vs. 0.90 QALYs in the chemotherapy group). Similarly, Patterson et al (2019 ) concluded that pembrolizumab was a cost-effective choice compared to chemotherapy from a Swedish healthcare perspective.…”

“…Highly relevant and robust data are extremely crucial. Since the quality of life is related to the progressive stage, the utility estimates for PF and PD states were assumed to be 0.80 and 0.75, respectively, based on similar UC studies ( Hale et al, 2021 ).…”