NEW YORK (Reuters Health) – For patients with metastatic melanoma, triplet therapy with atezolizumab and vemurafenib plus cobimetinib provides significant survival benefits over vemurafenib plus cobimetinib alone, but the regimen may not be cost-effective, researchers say.
“Economic evaluation is an important component to assess the incremental value of newly approved cancer treatments,” Dr. Chao Cai of the University of South Carolina in Columbia told Reuters Health by email. “The triplet combination of the PD-L1 inhibitor atezolizumab plus the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib was approved by the US Food and Drug Administration in July 2020 as the first triplet regimen for treating advanced melanoma patients with BRAF V600 mutations.”
“Adding immunotherapy to the targeted therapies could be cost-effective over a lifetime horizon if a long-lasting immunotherapeutic effect was sustainable and physicians would be willing to stop systematic immunotherapy after two years in the absence of disease progression,” he said. “It is noteworthy that we considered ‘cost-effective’ at the willingness to pay threshold of $150k/quality-adjusted life-year (QALY).”
As reported in JAMA Network Open, the economic evaluation study used a three-state partitioned survival model to assess the cost-effectiveness of atezolizumab with vemurafenib plus cobimetinib versus vemurafenib plus cobimetinib alone.
The primary outcomes of were expected life-years (LYs) gained and QALYs; costs; and the incremental cost-effectiveness ratio (ICER), expressed as cost per LYs and per QALYs saved.
Dr. Cai and colleagues found that adding atezolizumab to vemurafenib and cobimetinib provided an additional 3.267 QALYs compared with the doublet regimen, at an ICER of $271,669 per QALY, which is not considered cost-effective at the willingness-to-pay threshold of $150,000.
However, as Dr. Cai indicated, scenario analyses found that the triplet therapy could be cost-effective at 20-year (ICER, $121,432 per QALY) and 30-year ($98,092 per QALY) time horizons when both strategies were stopped after two years of treatment. Triplet therapy was also cost-effective and over a lifetime horizon ($122,220 per QALY) when only atezolizumab was stopped after two years of treatment.
The authors conclude, “These findings suggest that the atezolizumab and vemurafenib plus cobimetinib regimen provides significant survival benefits over vemurafenib plus cobimetinib alone, and a price reduction would be encouraged to maximize the value of its survival gain.”
Dr. Cai noted that the cost of the regimen is “probably not” similarly high outside of the U.S. because “some countries like Canada, the UK and Australia negotiate the prices of cancer drugs.”
Nonetheless, he advised, clinicians should “assess the need for treatments that go on for years, taking into account toxicities and costs.”
Dr. Rekha Chaudhary of the University of Cinncinati College of Medicine, a hematologist and oncologist specializing in skin cancer and melanoma, commented on the study in an email to Reuters Health. “In a patient with bulky and rapidly progressive disease who is very young and fit, the triplet regimen makes sense because you need to slow the disease down with the BRAF and MEK inhibitor, which work very quickly, while allowing the immunotherapy time to work; the immunotherapy works slower but gives you a durable response.”
“However,” she noted, “this is a highly selected patient population. There has been no overall survival benefit reported yet, so before we make final decisions, it would be nice to know if you really need all three drugs together at the same time or can you use them sequentially – for example, immunotherapy followed by the BRAF and MEK inhibitor.”
“I am not sure if cost is really an issue, as in a patient with metastatic BRAF-positive disease, we are already using all three drugs, just sequentially,” she concluded.
SOURCE: https://bit.ly/3cNfuTK JAMA Network Open, online November 11, 2021.