Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

Abstract

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

Cost-effectiveness of immunotherapies for advanced squamous non-small cell lung cancer: a systematic review

“…Liu 2021 [ 50 ] confirmed that compared to pembrolizumab monotherapy, pembrolizumab combined chemotherapy could add 0.22 QALY to life expectancy in patients with LSCC, with a corresponding marginal incremental cost of $3,449, and $15,613 /QALY of ICER.…”

“…Based on the 10 evaluation criteria of the Drummond Checklist, 13 of the 15 cost-effectiveness analyses were evaluated with perfect scores. The remaining two studies, Liu 2022 [ 50 ] and Shao 2022 [ 53 ], received a score of 9 for not providing a calculation method of the cost discount rate over time.…”

“…Based on current evidence, pembrolizumab monotherapy is more cost-effective as first-line treatment in patients with LSCC than combination chemotherapy [ 46 ], and pembrolizumab + chemotherapy has been shown to be more cost-effective than Pembrolizumab alone [ 50 ]. Sensitivity analysis of model parameters showed that in addition to first-line pembrolizumab + chemotherapy vs. pembrolizumab quantitative measures such as hazard ratios and AE that reflect the efficacy and safety of cancer therapy, drug price also had a considerable impact on our cost-effectiveness results.…”

“…Previous studies have also indicated that the factor most likely to reverse the results of cost-benefit analysis is the cost difference between two competing treatments [ 57 , 58 ]. Deterministic sensitivity analysis (DSA) results from the Liu et al [ 50 ] showed that for the LSCC patient population, pembrolizumab’s price per mg ranked first among all drugs in the DSA. However, the model still affirmed the cost-effectiveness of pembrolizumab + Chemo because of the inclusion of first-line treatment disruptions due to AE and decreased effectiveness due to AE in this analysis.…”