NEW YORK (Reuters Health) – For patients with metastatic melanoma, triplet therapy of atezolizumab and vemurafenib plus cobimetinib offers significant survival benefits over vemurafenib plus cobimetinib alone, but the therapy may not be cost-effective, researchers say.

“Economic evaluation is an important component in assessing the incremental value of newly approved cancer treatments,” said Dr. Chao Cai of the University of South Carolina at Columbia emailed Reuters Health. “The triplet combination of the PD-L1 inhibitor atezolizumab plus the BRAF inhibitor vemurafenib plus the MEK inhibitor cobimetinib was approved in July 2020 by the US Food and Drug Administration as the first triplet regimen for the treatment of patients with advanced melanoma approved with BRAF V600 mutations. “

“Adding immunotherapy to targeted therapies could be cost-effective over a lifetime horizon if long-term immunotherapeutic effects were sustained and doctors were willing to stop systematic immunotherapy after two years without the disease getting worse,” he said. “It is noteworthy that we considered the $ 150,000 / QALY willingness-to-pay threshold to be ‘affordable’.”

As reported in JAMA Network Open, the economic evaluation study used a three-state survival model to assess the cost-effectiveness of atezolizumab with vemurafenib plus cobimetinib compared to vemurafenib plus cobimetinib alone.

The primary endpoints were expected years of life gained (LYs) and QALYs; Costs; and the incremental cost effectiveness ratio (ICER), expressed as the cost per LYs and per QALYs saved.

Dr. Cai and colleagues found that adding atezolizumab to vemurafenib and cobimetinib delivered an additional 3,267 QALYs compared to the doublet regimen, at an ICER of $ 271,669 per QALY, which is not considered cost-effective given a willingness to pay threshold of $ 150,000.

As Dr. However, Cai stated, scenario analysis indicated that triplet therapy could be cost-effective after 20 years (ICER, $ 121,432 per QALY) and 30 years ($ 98,092 per QALY) if both strategies were discontinued after two years of treatment. Triplet therapy was also cost-effective and over the lifetime horizon ($ 122,220 per QALY) when atezolizumab alone was discontinued after two years of treatment.

The authors conclude: “These results suggest that therapy with atezolizumab and vemurafenib plus cobimetinib offers significant survival benefits over vemurafenib plus cobimetinib alone, and a price reduction would be encouraged to maximize the value of the survival gain.”

Dr. Cai noted that outside of the US, the regime’s costs “probably not” are similar because “some countries like Canada, the UK and Australia are negotiating cancer drug prices”.

Nonetheless, he advised clinicians “evaluate the need for years of treatment, considering 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. “For a very young and fit patient with voluminous and rapidly progressing disease, triplet therapy makes sense because you have to slow down the disease with the BRAF and MEK inhibitors, which work very quickly and give the immunotherapy time to take effect; the immunotherapy works slower, but gives you a permanent response. “

“However,” she noted, “this is a very select patient population. No overall survival benefit has been reported yet, so it would be nice to know if you really need all three drugs at the same time before we make final decisions. ”Time or you can use them sequentially – for example, immunotherapy followed by BRAF and MEK inhibitors. “

“I’m not sure the cost is really an issue because we’re already using all three drugs one at a time in a patient with metastatic BRAF-positive disease,” she concluded.

SOURCE: https://bit.ly/3cNfuTK JAMA Network Open, online November 11, 2021.

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