Is Biomarker Testing in NSCLC Cost-Effective?

August 2012 Vol 5, No 5, Special Issue ASCO 2012 Payers' Perspective
Caroline Helwick

Chicago, IL—“Economic evaluations of personalized medicine should incorporate the cost of testing for biomarkers,” said Natasha B. Leighl, MD, medical oncologist at Princess Margaret Hospital in Toronto, Canada, during a session on the cost of treating non–small-cell lung cancer (NSCLC) at ASCO 2012.

In essentially half of advanced adeno­carcinomas of the lung, a mutation is detected, and this will only increase as more is learned about the tumor’s biology. Although targeted agents are undoubtedly effective in selected populations, the cost-effectiveness of determining these patient groups has yet to be fully shown, Dr Leighl said.

Erlotinib Cost-Effective in Highly Targeted Group
The first targeted agent in NSCLC was erlotinib. In unselected patients in the pivotal NCIC CTG BR.21 trial, treatment with erlotinib led to an absolute 2-month improvement in median survival, representing a 30% reduction in mortality risk. A cost-effectiveness analysis of the pivotal trial showed that the drug itself is only marginally cost-effective.

Weighing the magnitude of survival benefit and expense, the incremental cost-effectiveness ratio (ICER) for erlotinib in the trial population was $94,638 (2007 Canadian dollars) per life-year gained.

However, when the analysis was restricted to groups that benefit most from the drug, treatment appeared to be cost-saving. The following ICERs were found among selected clinical and molecular subgroups, who also derived the greatest clinical benefit:

  • In never-smokers: ICER $39,487 versus $504,911 for current smokers
  • Epidermal growth factor receptor (EGFR) high copay: ICER $33,353 versus $109,792
  • EGFR mutation–positive: ICER $138,168 versus $87,994.

“The key in personalized medicine is defining the target population. You must identify the molecular subtype that will benefit,” Dr Leighl said.

A number of international studies have evaluated the cost-effectiveness of using EGFR tyrosine kinase inhibitors (ie, erlotinib and gefitinib) in patients with advanced NSCLC. Used first-line in patients with EGFR mutations, under the “test-and-treat” strategy, the ICERs have ranged from approximately €26,000 to €70,000 per quality-adjusted life-year (QALY), and in some circumstances the drugs were cost-saving.

In a study in which patients with the wild-type genotype received gefitinib third-line (based on the idea that the drug has modest benefit in the patients who do not have the mutation), the incremental benefit was diluted, and the ICER rose to >$80,000/QALY.

Is Crizotinib Cost-Effective in NSCLC?
The excitement over the targeted agent crizotinib for patients with NSCLC and the ALK rearrangement means that testing for this mutation will also become standard, with cost implications. “The cost varies by type of test and laboratory,” she said.

A 2012 study examined the impact of different predictive biomarker screening techniques and population enrichment criteria on the cost-effectiveness of treating ALK-positive NSCLC (Atherly AJ, et al. Br J Cancer. 2012;106: 1100-1106). The study showed the unit cost of FISH (fluorescence in situ hybridization) testing, which detects 100% of cases, to be $1400, whereas immunohistochemistry and the re­verse transcriptase polymerase chain reaction, which detect 60% to 70% of cases, cost only $600 to $900.  

The screening of all patients with advanced NSCLC for the ALK mutation using the FISH assay would be $106,707/QALY, but this decreases to $4756 when only a highly enriched population is screened (adenocarcinoma, never-smokers, EGFR-positive, KRAS wild-type), because this increases the biomarker frequency from 1.6% to 36%. But this approach would miss approximately half of the patients, resulting in some patients not being optimally treated.

“The cost would be reduced significantly because the likelihood of finding positive cases significantly increases,” Dr Leighl explained.

The study showed that cost-effectiveness of <$100,000 per QALY gained is not achievable at biomarker frequencies <5% (assuming drug costs of $1-$5000 per month and screening costs of $600-$1400 per person).

The researchers concluded that “Cost-effectiveness of oncology drugs whose prescribing is restricted to biomarker-positive subgroups should address the cost of detecting marker-positive patients. The cost of screening dominates at low frequencies, and strategies to improve cost-effectiveness, based on the assay cost, drug cost, and group screened, should be considered in these scenarios.”

Finally, Dr Leighl said, “The rapid evolution of testing technology and the costs should factor into policy decisions” about the targeted treatment of cancers, and this needs to be a continual process.

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