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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Tuesday, October 29, 2024
The primary results of the phase II ECHO-305/KEYNOTE-654 trial, which were published in the journal BMC Cancer, showed that the addition of the IDO1 inhibitor epacadostat to first-line therapy with the PD-1 inhibitor pembrolizumab was generally well tolerated in patients with PD-L1–high metastatic non–small cell lung cancer (NSCLC). However, according to Takaaki Tokito, MD, PhD, of Kurume University School of Medicine, Japan, and colleagues, the combination “did not demonstrate an improved therapeutic effect.”
Patients with high PD-L1 expression levels (tumor proportion score ≥ 50%) were randomly assigned to receive either 100 mg of oral epacadostat twice daily or a matching placebo (both n = 77) in combination with 200 mg of pembrolizumab every 21 days. Follow-up data were provided for a median of 6.8 and 7.0 months, respectively.
Similar confirmed objective response rates were reported between the epacadostat and placebo arms (32.5% vs 39.0%; one-sided P = .8000). The median durations of response were 6.2 months and not reached, respectively. Although not formally tested, the median progression-free survival was 6.7 months with epacadostat and 6.2 months with the placebo; the median overall survival was not reached in either arm.
The circulating levels of the main metabolite of tryptophan (kynurenine) were found to decrease (P < .01) and increase (P < .01) with epacadostat and the placebo, respectively, from day 1 of the first cycle to day 1 of the second cycle; however, according to the investigators, these levels were not normalized in most patients. The most frequently reported serious adverse events (≥ 2.0%) with epacadostat were pneumonia (4.0%), anemia (2.7%), atelectasis (2.7%), and pneumonitis (2.7%); they were pneumonia (3.9%), pneumonitis (2.6%), and hypotension (2.6%) with the placebo. Two patients died because of drug-related adverse events, both of whom were treated with the placebo.
“Evaluating higher doses of epacadostat that normalize kynurenine levels when given in combination with checkpoint inhibitors may be warranted,” the investigators concluded.
Disclosure: For full disclosures of the study authors, visit bmccancer.biomedcentral.com.
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