Cost-effectiveness of pembrolizumab plus chemotherapy vs cemiplimab plus chemotherapy for first-line metastatic non-small cell lung cancer: a US payer perspective using a matching-adjusted indirect comparison.

[AIM] Recent clinical guidelines recommend pembrolizumab plus chemotherapy and cemiplimab plus chemotherapy as key first-line treatment options for metastatic non-small cell lung cancer (mNSCLC). We evaluated the cost-effectiveness of these regimens from a US payer perspective.

[MATERIALS AND METHODS] A partitioned survival model with 1-week cycle, a 20-year horizon, and 3% annual discounting was developed. Clinical efficacy, safety, and utility inputs were derived from the KEYNOTE-189 (non-squamous histology), KEYNOTE-407 (squamous histology) and EMPOWER-Lung 3 Part 2 (both histologies). A matching-adjusted indirect comparison was conducted to compare efficacy outcomes between pembrolizumab plus chemotherapy and cemiplimab plus chemotherapy, with additional adjustment of overall survival to account for differences in subsequent immunotherapy use in control arms. Costs included drug acquisition and administration, adverse events, non-drug disease management, and terminal care. Outcomes included total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Scenario, deterministic, and probabilistic sensitivity analyses were performed.

[RESULTS] In non-squamous mNSCLC, pembrolizumab plus chemotherapy versus cemiplimab plus chemotherapy increased discounted costs by $43,131 ($335,194 vs $292,062) and QALYs by 0.71 (2.69 vs 1.98), yielding an ICER of $60,957/QALY. In squamous mNSCLC, incremental costs were $34,675 ($276,431 vs $241,756) for a 0.43 QALY gain (2.32 vs 1.89), yielding an ICER of $80,218/QALY. In the pooled mNSCLC population, incremental costs were $41,601 ($324,561 vs $282,960) with 0.66 additional QALYs (2.62 vs 1.97), and resulting ICER of $64,442/QALY. The model is most sensitive to the OS hazard ratio between regimens. Probabilistic sensitivity analysis suggests a high probability that pembrolizumab plus chemotherapy is cost-effective at commonly cited US willingness-to-pay (WTP) thresholds ($100,000/QALY and $150,000/QALY) considering uncertainties.

[LIMITATIONS AND CONCLUSIONS] After MAIC and subsequent immunotherapy adjustments, pembrolizumab plus chemotherapy showed improved overall survival and progression-free survival versus cemiplimab plus chemotherapy in both non-squamous and squamous metastatic NSCLC at modest incremental cost.