Immunotherapy Guided by Immunohistochemistry PD-L1 Testing for Patients with NSCLC: A Microsimulation Model-Based Effectiveness and Cost-Effectiveness Analysis.

Background: On the basis of immunohistochemistry PD-L1 testing results, patients with advanced non-small cell lung cancer (NSCLC) are treated differently. Theoretically, patients with high PD-L1 expression (50% or 1%) should receive PD-1 monotherapy for fewer adverse reactions and cost savings from avoiding chemotherapy; however, there is controversy surrounding the cut-off criteria (1% or 50%) for immunohistochemistry testing and threshold for PD-1 monotherapy.

Objective: This study aims to predict the effectiveness and cost-effectiveness of different immunotherapy strategies for patients with NSCLC in China from the healthcare system perspective.

Patients and methods: A microsimulation model was developed to evaluate the effectiveness and cost-effectiveness of three treatment strategies: PD-L1 testing (1%) (PD-1 monotherapy for those with PD-L1 expression at 1% threshold, and combination with chemotherapy for others with immunohistochemistry testing), PD-L1 testing (50%) (PD-1 monotherapy for those with PD-L1 expression at 50% threshold, and combination with chemotherapy for others with immunohistochemistry testing), and No PD-L1 testing (PD-1 combined with chemotherapy without immunohistochemistry testing). The model assumed 1000 patients per strategy, with each patient entering a unique clinical path prior to receiving treatment on the basis of PD-L1 test results. Clinical inputs were derived from clinical trials. Cost and utility parameters were obtained from the database and literature. One-way probabilistic sensitivity analyses (PSA) and six scenario analyses were used to test the model's robustness.

Results: The study revealed a hierarchy of survival benefits across three strategies, with No PD-L1 testing demonstrating the most survival advantage, followed by PD-L1 testing (50%), and finally, PD-L1 testing (1%). The comparative analysis demonstrated that No PD-L1 testing significantly enhanced overall survival (OS) (HR 0.85, 95% CI 0.78-0.93), progression-free survival (HR 0.82, 95% CI 0.75-0.90), and progression-free2 survival (PFS2) (HR 0.91, 95% CI 0.83-0.99) when juxtaposed against PD-L1 testing (1%). However, these improvements were not as pronounced when compared with PD-L1 testing (50%), particularly in relation to PFS, PFS2, and OS. The cost-effectiveness analysis further unveiled incremental cost-utility ratios (ICUR), with No PD-L1 testing versus PD-L1 testing (50%) at $34,003 per quality-adjusted life year (QALY) and No PD-L1 testing versus PD-L1 testing (1%) at $34,804 per QALY. In parallel, the ICUR for PD-L1 testing (50%) versus PD-L1 testing (1%) stood at $35,713 per QALY. Remarkably, the PSA result under a willingness-to-pay (WTP) threshold of $10,144 per QALY, with a 100% probability, demonstrated PD-L1 testing (1%) as the most cost-effective option.

Conclusions: The survival benefits of PD-1 monotherapy for high expression with PD-L1 immunohistochemistry testing are inferior to those of PD-1 combined with chemotherapy without testing, but it is found to be more cost-effective at the WTP thresholds in China and holds great potential in increasing affordability and reducing the economic burden.