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Alexander Drilon, MD

Gregory J. Riely, MD, PhD

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Dutch Team Examines the Cost-Effectiveness of Entrectinib in NTRK-Positive Cancer

By: Celeste L. Dixon
Posted: Tuesday, November 15, 2022

Given the recent regulatory approvals of the first two histology-independent cancer drugs, entrectinib and larotrectinib, can we also conclude they are cost-effective treatment options compared with standard-of-care treatment for patients with NTRK gene fusions? Not yet, according to Maureen Rutten-van Mölken, PhD, of Erasmus University Rotterdam, the Netherlands, and colleagues, who shared their findings in the journal Value in Health. However, they added, “the study results are very uncertain because of data limitations.”

At this point, two major factors are at play: NTRK fusions are rare, and genetic testing is not inexpensive enough or applied broadly enough. So, in the future, entrectinib and larotrectinib might be cost-effective if the costs of the RNA next-generation sequencing panels that can identify NTRK fusions decreased substantially, or if broad genetic testing of patients with cancer was to become standard practice. “Payers should focus on policies supporting a reduction in the costs of testing,” the team recommended.

The investigators wanted to know whether “testing”—defined as testing patients with cancer for NTRK gene fusions and then providing entrectinib if they tested positive or standard of care if they tested negative—would be cost effective compared with “no testing”—defined as standard-of-care treatment provided to all patients. “Given that only single-arm trial data are available for entrectinib, we estimated a synthetic control arm that accounted for the prognostic value of NTRK fusions,” Dr. Rutten-van Mölken and co-investigators wrote.

Ultimately, they found that in the Netherlands, entrectinib—and probably, by extension, larotrectinib—is not cost-effective. “Testing” had higher per-patient quality-adjusted life-years (QALY) and costs than “no testing,” with differences of 0.0043 and €732, respectively.

“This corresponded to an incremental cost-effectiveness ratio of €169,957 per QALY and, using a cost-effectiveness threshold of €80,000 per QALY, an incremental net monetary benefit of €388,” they explained. “When excluding the costs of genetic testing for NTRK fusions, the incremental cost-effectiveness ratio was reduced to €36,290 per QALY, and the incremental net monetary benefit increased to €188.”

Disclosure: The study authors’ disclosure information can be found at valueinhealthjournal.com.


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