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

Qiao Liu,Chongqing Tan,Zhen Zhou,Lidan Yi,Liubao Peng,Xiaomin Wan,Xia Luo,Xiaohui Zeng

doi:10.3389/fphar.2021.803626

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.

Highlights

Lung cancer is the leading cause of cancer-related deaths in the United States and globally, contributing to roughly 25% of cancer-related deaths
Through mathematical modeling and network metaanalysis (NMA), we evaluated the cost-effectiveness of first-line pembrolizumab monotherapy (Pembro)+Chemo relative to first-line Pembro among metastatic nonsmall-cell lung cancer (NSCLC) patients with programmed death-ligand 1 (PD-L1) expression ≥50% from the United States (US) health care sector perspective
In our base case analysis, we found that in non-squamous NSCLC patient population, first-line Pembro+Chemo was superior to first-line Pembro in survival, but was associated with an overwhelming healthcare cost

Summary

Introduction

Lung cancer is the leading cause of cancer-related deaths in the United States and globally, contributing to roughly 25% of cancer-related deaths. Gene therapies targeting the oncogenic drivers such as sensitizing epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations, has showed a great efficacy on the management of NSCLC (Brahmer et al, 2015; Borghaei et al, 2015; Garon et al, 2015; Herbst et al, 2016; Kazandjian et al, 2016; Reck et al, 2016; Rittmeyer et al, 2017; Barlesi et al, 2018; Gandhi et al, 2018; Paz-Ares et al, 2018; Antonia et al, 2019; Mok et al, 2019; Reck et al, 2021) These therapies do not take effect in patients with metastatic NSCLC without driver molecular alterations, who constitutes approximately 80% of the NSCLC cases (Aisner and Marshall, 2012). The latest National Comprehensive Cancer Network (NCCN) guidelines for NSCLC recommend replacing traditional chemotherapies with ICIs-containing regimens as the preferred first-line therapies for NSCLC when PD-L1 expresses in at least 50% of tumor cells (National Comprehensive Cancer Network, 2021)

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Discussion

Conclusion