Treating Advanced Non-small Cell Lung Cancer Patients With Immune Checkpoint Inhibitors: A Pharmacoeconomic Research

Objectives: As novel immune checkpoint inhibitors(ICIs)are gradually being approved and expanded the indications clinically,the treatment patterns for the immunotherapy in the patients with advanced non-small cell lung cancer(NSCLC)are changing.Different with the clinical trials,these new ICIs also increase the disease burden along with the prolonged clinical benefits in the real-world clinical practices.This study aims to make a real-world observational research on the second-line treatment patterns for patients with the advanced NSCLC,assess the economic burden and healthcare resource utilization(HCRU)after progression and also conduct a pharmacoeconomic analysis on the first-line immunotherapy among the patients who have positive PD-L1 expression,basing on the clinical trial KEYNOTE-042.Methods: An observational study was conducted with electronic medical records from Shanghai Chest Hospital on patients≥ 18 years old with a diagnosis of NSCLC.Hospitalized patients treated with nivolumab or another second-line chemotherapy between May 2018 and August 2019 were included.Second-line therapy agents,clinical characteristics,disease progression,HCRU and other associated costs were assessed.After that,key clinical parameters were derived from a subgroup of PD-L1 expression ≥1%from a new reporting clinical trial KEYNOTE-042.A non-homogeneous Markov cycle was built in R with a 10-year horizon.Costs of health resource utilization were acquired and estimated form the retrospective observational study.One-way sensitivity and probability sensitivity analyses were conducted for the uncertainty of this model.Results: A total of 296 patients were included in this study,of whom 187 were treated with nivolumab and 109 were treated with chemotherapy.In the nivolumab group,74.33% received monotherapy at doses of 140 mg,180 mg,200 mg,240 mg or another dose,and nearly half were treated with 180 mg or 200 mg.Docetaxel(84.40%)and pemetrexed were selected as second-line chemotherapies.The mean total cost of nivolumab monotherapy and docetaxel was 21,357.82 yuan and 6,327.42 yuan,respectively.Nivolumab decreased inpatient days to 1.95 days per patient per cycle,while chemotherapy(docetaxel)rose inpatient days to 3.12 days per patient per cycle.Laboratory testing cost was controlled,and total computed tomography(CT)and chest B ultrasound events were reduced in the nivolumab group.Regarding the costs and HCRU associated with the treatment cycles,nivolumab showed a more stable trend.However,nivolumab did not prolong progression-free survival(PFS)compared with second-line chemotherapy(the median PFS was 2.8months for both).With the 10-year time horizon,the pembrolizumab first-line therapy group gained 1.143 life years(LYs)and 1.064 quality-adjusted life years(QALYs)with a total cost of $100,273.24,while in platinum-based first-line chemotherapy group,they gained 0.674 LYs and 0.848 QALYs with a total cost of $61,506.In the base-case analysis,the incremental cost-effectiveness analysis ratio(ICER)was $181,390.50/ QALY.The most sensitive parameter was the drug cost of pembrolizumab,followed by the utilities of health states.Conclusion: In the real-world treatment patterns,compared with second-line chemotherapy,nivolumab second-line therapy decreased the hospitalization duration and the costs for diagnosis.However,nivolumab was still too expensive to burden with no significantly prolonging PFS.And when PD-L1 expression positive advanced NSCLC patients were treated with pembrolizumab as first-line therapy(docetaxel followed as second-line therapy),it is not a cost-effective treatment strategy,comparing with the platinum-based first-line therapy(nivolumab followed as second-line therapy).