Are New Checkpoint Inhibitors Cost-Effective for Metastatic NSCLC Therapy?

Pembrolizumab offers survival advantages at a much lower cost over atezolizumab.

An economic simulation found that the addition of atezolizumab (Tencentriq) to bevacizumab (Avastin), carboplatin, and paclitaxel (Taxol) as a first-line treatment for metastatic nonsquamous non–small cell lung cancer (NSCLC) was not a cost-effective option, though it does provide survival benefit. Pembrolizumab (Keytruda), in contrast, offers survival advantages at a much lower cost than atezolizumab. 

“The implications of PD-1 or PD-L1 immune checkpoint inhibitor approval in the first-line treatment of nonsquamous NSCLC are considerable, given the potential population of patients eligible to receive these therapies and their high cost,” wrote study authors led by Steven D. Criss, BS, of Massachusetts General Hospital in Boston. “Cost-effectiveness analysis can be an important tool to assess whether new therapies provide clinical benefit at a justifiable cost, which is increasingly necessary as approved indications continue to expand.” Pembrolizumab’s cost effectiveness has previously been studied, but the newest approved immune checkpoint inhibitor in this setting, atezolizumab, has not.    

The authors created a primary microsimulation model to assess the combination of atezolizumab, bevacizumab, carboplatin and paclitaxel; a second model was then used to compare this to pembrolizumab along with the same agents. Treatment strategies and other conditions were derived from results of the IMpower150 and KEYNOTE-189 trials, and one million patients were simulated in each model. The results were published online ahead of print on September 25 in JAMA Network Open.

In a control case where 1,00,000,000 patients were treated only with bevacizumab, carboplatin, and paclitaxel, there was a mean cost of $112,551, and a mean survival of 1.48 quality-adjusted life-year (QALY) per patient. The addition of atezolizumab increased the mean cost to $244,166 per patient, with a mean survival of 2.13 QALYs per patient. This yielded an estimated incremental cost-effectiveness ratio of $201,676 per QALY.

In the simulation where pembrolizumab was used instead of atezolizumab, the mean cost was $226,282 per patient, with a mean survival of 2.45 QALYs per patient. This yielded an incremental cost-effectiveness ratio of $116,698 per QALY, which came closer to a pre-specified willingness-to-pay threshold of $100,000 per QALY.   

The authors wrote that atezolizumab along with bevacizumab, carboplatin, and paclitaxel “would not be a cost-effective option at a willingness-to-pay threshold of $100,000 per QALY…. Price reductions remain the most pragmatic solution for the insufficient cost-effectiveness of these PD-1 or PD-L1 immune checkpoint inhibitors in the treatment of metastatic nonsquamous NSCLC.”         

In an accompanying editorial, Darren R. Brenner, PhD, of the University of Calgary in Canada, wrote that identifying subpopulations of patients with an improved response to immunotherapy may offer an alternative method to increase the agents’ cost-effectiveness.

“By reducing the size of the approved populations to those for whom response to targeted therapies is most pronounced, the costs may be offset by larger gains in QALYs,” he wrote. 


Criss SD, Mooradian MJ, Watson TR, Gainor JF, Reynolds KL, Kong CY. Cost-effectiveness of Atezolizumab Combination Therapy for First-Line Treatment of Metastatic Nonsquamous Non–Small Cell Lung Cancer in the United States. JAMA Netw Open. Published online September 25, 20192(9):e1911952. doi:10.1001/jamanetworkopen.2019.11952