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ICER: TKIs, PD-1 agents yield ‘uncertain’ clinical, financial benefit for NSCLC
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The cost-effectiveness and clinical benefit of tyrosine kinase inhibitors and PD-1 agents for the treatment of non–small cell lung cancer varied across patient groups and appeared uncertain in some cases, according to a draft evidence report issued by the Institute for Clinical and Economic Review.
The Institute for Clinical and Economic Review (ICER) draft report is open for public comment until Sept. 16.
Although chemotherapy has been the standard of care for advanced NSCLC, advances in precision medicine — including the use of TKIs and immunotherapies — have offered additional treatment options.
“Questions remain, however, regarding the appropriate sequence of treatment with these newer agents, the role of certain tests to inform treatment decisions, and management of the costs of these therapies,” the report stated.
Researchers identified clinical trial findings, reviews and comparative cohort studies to evaluate TKIs and PD-1 inhibitors compared with chemotherapy in:
- treatment-naive patients with EGFR–positive tumors;
- patients without a driver mutation who are treatment naive for advanced disease;
- patients without a driver mutation who have progressed after first-line treatment with a platinum-based chemotherapy doublet; and
- patients with EGFR–positive tumors that have progressed on first- or second-line TKIs.
The TKIs evaluated included afatinib (Gilotrif, Boehringer Ingelheim), erlotinib (Tarceva; Genentech, Astellas Pharma) and gefitinib (Iressa, AstraZeneca). Researchers also evaluated the PD-1 agents atezolizumab (Tecentriq, Genentech/Roche), nivolumab (Opdivo, Bristol-Meyers Squibb) and pembrolizumab (Keytruda, Merck).
In the review of TKI studies, researchers determined there was inadequate evidence to distinguish between the three agents in terms of OS and quality-of-life benefits. All three agents improved PFS and quality of life compared with platinum doublet chemotherapy in head-to-head trials; however, due to high rates of crossover, OS benefit was uncertain.
Because the studies of PD-1 agents used different assays to measure PD-L1, researchers determined there was inadequate evidence to distinguish between the three immunotherapies.
An analysis of these studies showed patients with advanced disease without a driver mutation who progressed after a platinum doublet experienced improved outcomes with immunotherapy, as did patients with PD-1–expressing tumors.
“However, only a minority of patients overall respond to these agents, even among those with high PD-L1 levels on assays,” the report stated. “Conversely, even with negative PD-L1 level results, some patients do respond to PD-1 immunotherapy. Because of the limited follow-up in the existing studies, we are uncertain of how large the benefit is for the minority of patients who do respond to these agents.”
Researchers used the commonly accepted threshold of $50,000 to $150,000 per quality-adjusted life-year gained to determine cost-effectiveness. Cost-effectiveness ratios ranged between approximately $110,000 and $130,000 per quality-adjusted life-year gained in patients treated with TKIs, and between $208,000 and $250,000 in patients treated with PD-1 agents.
However, both deterministic and probabilistic sensitivity analyses suggested uncertainty in these findings.
“At current wholesale acquisition costs, the estimated cost-effectiveness of each of the TKIs appears to fall within commonly accepted thresholds,” the report said. “While the cost-effectiveness of PD-1 immunotherapies exceeds these thresholds, there is greater uncertainty in these findings given variability in estimates of overall and progression-free survival.”
In response to the draft report, Pharmaceutical Research and Manufacturers of America (PhRMA), Personalized Medicine Coalition, and other groups have released statements about their concerns.
The report suggests there is a “disconnect” between what ICER and what oncologists define as value, Holly Campbell, senior director of communications at PhRMA, wrote in a blog post.
“As stakeholders increasingly call for movement toward more personalized, individualized care, ICER persists with static, one-size-fits all assessments of value,” Campbell wrote. “This is in direct contradiction to the objectives of widely heralded policy initiatives like the Precision Medicine Initiative and the Cancer Moonshot.”
Because patients with NSCLC are likely to progress and develop resistance mutations, it’s imperative that they have several treatment options, Campbell added.
“While the rest of the health care community moves forward together, ICER has dug in its heels,” she wrote. “If they continue to make judgments of value that ignore the complexities of treating patients with diseases like NSCLC, they will be left behind in the shift toward a personalized, value-driven health care system.”
The final evidence report is expected Sept. 28 and will be discussed at a public meeting held by the Midwest Comparative Effectiveness Public Advisory Council on Oct. 20. – by Kristie L. Kahl
References:
Institute for Clinical and Economic Review. Draft Evidence Report: Non–Small Cell Lung Cancer. Published on August 19, 2016. Accessed on September 6, 2016.
Campbell H. The Catalyst. Published on September 1, 2016. Accessed on September 6, 2016.