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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Monday, December 23, 2024
The combination of the SINE (selective inhibitor of nuclear export) inhibitor selinexor and docetaxel showed activity in patients with advanced KRAS-mutant non–small cell lung cancer (NSCLC), particularly those with TP53 wild-type tumors. In this multicenter phase I/II trial, David Gerber, MD, of the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, Dallas, and colleagues discovered that the regimen was generally well tolerated, and TP53 status emerged as a key determinant of clinical benefit, suggesting its potential as a predictive biomarker for treatment response.
“Our results suggest that selinexor could be a useful addition to our toolbox to treat lung cancer and could offer hope for other cancers with KRAS mutations,” said Dr. Gerber in an institutional press release.
This trial evaluated the safety, tolerability, and efficacy of selinexor combined with docetaxel in patients with previously treated advanced KRAS-mutant NSCLC. Selinexor was administered weekly starting 1 week before docetaxel to assess pharmacodynamic effects. A total of 40 patients (median age, 66 years; 55% female; 85% White) were enrolled.
Of 32 efficacy-evaluable patients, 22% achieved partial responses, and 56% had stable disease. Outcomes were significantly better in TP53 wild-type cases compared with TP53-altered cases, with higher response rates (27% vs 9%) and longer progression-free survival (7.4 vs 1.8 months; hazard ratio = 0.2; P = .003). Changes in serum lactate dehydrogenase levels after treatment with selinexor and before docetaxel initiation further correlated with TP53 status.
The maximum tolerated dose of selinexor was 60 mg, administered orally weekly with docetaxel at 75 mg/m² intravenously every 3 weeks. Common adverse events included nausea (73%; 8% grade ≥ 3), fatigue (70%; 5% grade ≥ 3), neutropenia (65%; 60% grade ≥ 3), and diarrhea (58%; 10% grade ≥ 3).
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.
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