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PLoS One. 2020 Jan 29;15(1):e0228288. doi: 10.1371/journal.pone.0228288. eCollection 2020.

Cost-effectiveness of pembrolizumab for advanced non-small cell lung cancer patients with varying comorbidity burden.

Author information

Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA, United States of America.
Division of General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Division of Pulmonary and Critical Care Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Harvard Medical School, Boston, MA, United States of America.



While previous cost-effectiveness studies on pembrolizumab in stage IV non-small cell lung cancer (NSCLC) have found these regimens to be cost-effective, their reliance on randomized controlled trial (RCT) data with strict inclusion criteria limits generalizability to patients with comorbidities. We estimated the cost-effectiveness of first-line pembrolizumab for patients with various comorbidities.


In our base case analysis, we studied pembrolizumab plus chemotherapy (pembrolizumab combination therapy) versus chemotherapy alone. In a secondary analysis, we considered only patients with PD-L1 expression of at least 50% (PD-L1-high) and evaluated pembrolizumab monotherapy, pembrolizumab combination therapy, and chemotherapy alone. Microsimulation models were developed for the base case and the PD-L1-high analyses. To estimate outcomes of patients with differing comorbidities, we combined survival data from patients with few or no comorbidities from the RCTs with estimates from the general population obtained from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Comorbidity burden level was divided into three groups based on the Charlson score (equal to 0, 1, or 2+); patients with various other specific comorbidities were also analyzed. Incremental cost-effectiveness ratios (ICER) were compared to a willingness-to-pay (WTP) threshold of $100,000/quality-adjusted life-year (QALY).


In the Charlson 0, Charlson 1, and Charlson 2+ patient populations, estimated ICERs for pembrolizumab combination therapy in the base case model were $173,919/QALY, $175,165/QALY, and $181,777/QALY, respectively, compared to chemotherapy. In the PD-L1-high model, the Charlson 0, Charlson 1, and Charlson 2+ patients had ICERs of $147,406/QALY, $149,026/QALY, and $154,521/QALY with pembrolizumab combination therapy versus chemotherapy. Pembrolizumab monotherapy was weakly dominated for each comorbidity group in the PD-L1-high model.


For patients with stage IV NSCLC and varying comorbidity burden, first-line treatment with pembrolizumab does not represent a cost-effective strategy compared to chemotherapy. Resources should be focused on collecting immunotherapy survival data for more representative NSCLC patient populations.

Conflict of interest statement

Dr. Wisnivesky is a member of the research board of EHE International and has received consulting honorarium from Quintiles, Merck, and AstraZeneca and research grants from Sanofi and Quorum. All other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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