Assessing the Cost–Benefit of Immune Checkpoint Inhibitors
Although immune checkpoint inhibitors can significantly extend survival of patients with metastatic disease, more than 50% of the patients who use them have serious, grade 3 to grade 5 adverse events. These toxicities comprise a considerable proportion of the total number of immune checkpoint inhibitors, especially those that target PD-1, said Neil T. Mason, MBA, Personalized Medicine Strategist, Moffitt Cancer Center, Tampa, FL, who presented his study results at a poster session at the 2016 American Society of Clinical Oncology annual meeting.
Immune checkpoint inhibitors, such as the PD-1 inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda), and the CTLA-4 inhibitor ipilimumab (Yervoy), have demonstrated significant improvements in survival for patients with metastatic disease, despite common toxicities.
“The cost of managing toxicities associated with immune checkpoint inhibitor therapy is not insignificant and could change the value-to-cost ratio between equally effective drugs, such as nivolumab and pembrolizumab,” Mr Mason said.
“Single-agent immune checkpoint therapy yields a clinical response in 11% to 32% of patients. Unfortunately, efficacy and toxicity are not clearly correlated, meaning some patients receive benefit without experiencing toxicities, while others suffer severe adverse events with no benefit,” he said.
Although results from clinical practice differ from those of clinical trials, the majority of economic analyses use results from clinical trials to determine the cost-effectiveness of drugs. Therefore, Mr Mason and colleagues’ model used patient data from the Moffitt Cancer Center to estimate the average cost of treatment with immune checkpoint inhibitors.
These costs were based on the average treatment duration and reported toxicity rates from the electronic health record and billing data. The weighted average cost of managing toxicities associated with each drug was compared with the estimated total cost of therapy.
The estimated cost of therapy for ipilimumab was $101,290—the highest of the 3 treatment regimens. The estimated costs of therapy for nivolumab and pembrolizumab were $30,078 and $58,008, respectively.
The estimated costs of managing side effects were similar for all 3 drugs, with nivolumab being the most expensive. Nivolumab’s toxicity-related costs were driven by high rates of peripheral neuropathy (33.7%), dyspnea (31.7%), and ventricular arrhythmia (18.8%), reported Mr Mason.
The estimated total cost of therapy (including toxicities) per patient for ipilimumab was $109,506, driven by its steep price. By comparison, the estimated total cost for pembrolizumab treatment was $66,555, and $47,686 for nivolumab. “Nivolumab and pembrolizumab therapy cost less on average than ipilimumab due to the high cost per dose of ipilimumab and average number of doses received for each drug,” Mr Mason said.
Nivolumab and pembrolizumab are less expensive and yield better clinical outcomes than ipilimumab, which will likely increase the use of PD-1 inhibitors and replace ipilimumab therapy in the clinical pathways, he added.
Novel Diagnostics Needed
Clinical trials combining a PD-1 inhibitor with a CTLA-4 inhibitor have demonstrated significant improvements in efficacy, but these clinical gains have been associated with a dramatic increase in toxicities.
“Extrapolating from this model, it is clear that these regimens would be extremely, and possibly prohibitively, costly,” said Mr Mason.
“To improve the cost-benefit ratio of expensive immunotherapies, new diagnostics must be developed to identify patients most likely to respond, or those most likely to suffer from catastrophic toxicities that could be prevented or preemptively managed to contain the overall cost of care,” he concluded.