Non–Small Cell Lung Cancer: Epidemiology,Screening, Diagnosis,and Treatment

Lung cancer remains the leading cause of cancer deaths in the United States. In the past decade, significant advances have been made in the science of non–small cell lung cancer (NSCLC). Screening has been introduced with the goal of early detection. The National Lung Screening Trial found a lung cancer mortality benefit of 20% and a 6.7% decrease in all-cause mortality with the use of low-dose chest computed tomography in high-risk individuals. The treatment of lung cancer has also evolved with the introduction of several lines of tyrosine kinase inhibitors in patients with EGFR, ALK, ROS1, and NTRK mutations. Similarly, immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of NSCLC treatment. Furthermore, the results of new trials continue to help us understand the role of these novel agents and which patients are more likely to benefit; ICIs are now part of the first-line NSCLC treatment armamentarium as monotherapy, combined with chemotherapy, or after definite chemoradiotherapy in patients with stage III unresectable NSCLC. Expression of programmed cell death protein-ligand 1 in malignant cells has been studied as a potential biomarker for response to ICIs. However, important drawbacks exist that limit its discriminatory potential. Identification of accurate predictive biomarkers beyond programmed cell death protein-ligand 1 expression remains essential to select the most appropriate candidates for ICI therapy. Many questions remain unanswered regarding the proper sequence and combinations of these new agents; however, the field is moving rapidly, and the overall direction is optimistic.     

Economic Burden of Checkpoint Inhibitor Immunotherapy for the Treatment of Non–Small Cell Lung Cancer in US Clinical Practice

PurposeThe efficacy of checkpoint inhibitor (CPI) immunotherapy in patients with non–small cell lung cancer (NSCLC) is limited by a lack of strongly predictive response markers, subjecting patients to potential underutilization of alternative effective treatments, increased risk for futile care, and unnecessary costs. Here, we characterize the extent to which basic molecular tumor-marker testing has been performed for NSCLC therapy selection in the United States, and compare medical resource utilization and costs in CPI-treated patients versus CPI-eligible patients treated with other therapies.MethodsWe identified a cohort of CPI-treated patients with NSCLC and a propensity score–matched cohort of CPI-eligible patients with NSCLC treated with non-CPI therapies (3095 patients in each group), using US administrative claims data covering the pre- and postinitial FDA-approval period for nivolumab, pembrolizumab, and atezolizumab (October 2012 to September 2017). We describe the utilization of recommended baseline molecular testing for CPI selection (pre–index date for CPI or other anticancer therapy), including programmed death ligand 1 (PD-L1) immunohistochemistry, ALK rearrangement and EGFR mutation testing, and pre- and postindex treatment patterns. All-cause medical resource utilization and semiannual total reimbursement (costs) were compared between CPI-treated and non-CPI–treated patients.FindingsAt baseline, in the propensity score–matched CPI- and non–CPI-treated patient cohorts, mean PD-L1 immunohistochemistry test utilization for CPI selection was moderate (0.6 vs 0.7 per patient, respectively). However, we observed much lower mean utilization of testing for EGFR mutations (0.1 vs 0.1 per patient) and ALK rearrangements (0.1 vs 0.2 per patient). Postindex, the use of both chemotherapy and ALK- and EGFR-targeted therapies were decreased in both cohorts. The CPI-treated group had significantly higher mean medical resource utilization in nearly all categories in the postindex period, and total per-patient semiannual costs, than did the CPI-eligible patients who received other therapies (141,537 vs 75,429 US dollars [USD]; P < 0.0001), driven by CPI drug reimbursement. Median (interquartile range) time on CPI was longest with pembrolizumab (113 [106–127] days), followed by nivolumab (105 [97–106] days) and atezolizumab (64 [50–85] days). Despite being associated with the lowest drug cost and the shortest treatment duration, atezolizumab was associated with the highest mean total per-patient semiannual costs (160,540 USD) compared with pembrolizumab (153,003 USD) and nivolumab (138,542 USD).ImplicationsThe advent of CPI treatment for NSCLC has added substantial care-related costs for patients and payers, concurrent with underutilization of minimum recommended molecular testing for therapy selection. Broad uptake of panel-based comprehensive targeted-therapy and immunotherapy profiling can promote optimal treatment selection and sequencing, reduce the likelihood of futile treatment, and further improve patient outcomes.     

Cost-effectiveness of Osimertinib as a Second-line Treatment in Patients With EGFR-mutated Advanced Non–Small Cell Lung Cancer in China

PurposeTo assess the cost-effectiveness of osimertinib used as a second-line treatment after failure of epidermal growth factor receptor tyrosine kinase inhibitor therapy for advanced non–small cell lung cancer (NSCLC) in China.MethodsFrom the perspective of China's health care system, a Markov model was used for estimating the costs and health outcomes of osimertinib and 4 platinum-based chemotherapies, including pemetrexed + platinum (PP), gemcitabine + platinum (GP), docetaxel + platinum (DP), and paclitaxel + platinum (TP). Two scenarios were considered, one in all confirmed patients with T790M-positive disease (scenario 1) and the other in all patients whose disease progressed after epidermal growth factor receptor tyrosine kinase inhibitor therapy, which consisted of patients with T790M-positive or T790M-negative NSCLC (scenario 2). Clinical data for transition probabilities and treatment effects were obtained from published clinical trials. Health care resource utilization and costs were derived from local administrative databases and published literature. Deterministic and probabilistic sensitivity analyses were conducted to assess the uncertainty of the results.FindingsIn the base-case analysis, compared with the 4 platinum-based chemotherapies, osimertinib yielded an additional 0.671 to 0.846 quality-adjusted life-year (QALY), with incremental costs of 15,943 to 20,299 USD in scenario 1, and an additional 0.376 to 0.808 QALY with incremental costs of 9710 to 15,407 USD in scenario 2. In the probabilistic sensitivity analysis, the probabilities that osimertinib would be cost-effective were 57.7% in scenario 1 and 58.4% in scenario 2 if the willingness-to-pay threshold were 30,000 USD/QALY, and probabilities would be more than 75 % in both scenarios if the willingness-to-pay threshold were 50,000 USD/QALY.ImplicationsOsimertinib is likely to be cost-effective when used as a second-line treatment of advanced NSCLC in China based on the latest reimbursement price of osimertinib through National Reimbursement Drug List negotiation.