FDA-Approved Drug Shows Promise in Advanced NSCLC
Selinexor shows promise in treating KRAS-mutated NSCLC, achieving tumor control in 80% of cases during a clinical trial.
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A clinical trial led by researchers at UT Southwestern Medical Center has demonstrated that selinexor, an FDA-approved drug for multiple myeloma and lymphoma, may also benefit patients with non-small cell lung cancer (NSCLC) carrying KRAS mutations. The findings, published in Clinical Cancer Research, suggest selinexor could address a significant unmet need for effective treatments in this challenging cancer subset.
KRAS mutations
Changes in the KRAS gene that lead to abnormal cell signaling and growth, commonly seen in many cancers, including NSCLC.
Selinexor
A nuclear export inhibitor that disrupts cancer cell processes by blocking proteins responsible for exporting molecules out of the cell nucleus.
Non-small cell lung cancer (NSCLC)
The most common type of lung cancer, accounting for about 85% of cases.
KRAS mutations and NSCLC
KRAS mutations are found in approximately 25% of NSCLC cases, representing one of the most common and challenging-to-treat subsets of lung cancer. While targeted therapies such as sotorasib and adagrasib have recently emerged, their efficacy is limited to specific KRAS mutations and provides only modest benefits, typically lasting about six months. This underscores the need for new approaches to manage these cancers.
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Subscribe for FREEClinical trial design and results
The trial involved 40 NSCLC patients with various KRAS mutation types who had progressed after multiple treatments. Participants received weekly oral doses of selinexor, a nuclear export inhibitor, followed by docetaxel, a chemotherapy agent. Tumor size and treatment safety were assessed using imaging and blood tests.
TP53 mutations
Alterations in the TP53 gene, which normally suppresses tumor growth, often associated with resistance to cancer therapies.
Nuclear export inhibitors
Drugs that target the transport of proteins and RNA from the nucleus to the cytoplasm, disrupting cancer cell function.
The combination therapy showed promising results:
- Tumor control was achieved in approximately 80% of cases, surpassing expectations for docetaxel alone.
- Selinexor was effective across different KRAS mutation types.
- Patients with TP53 mutations, a tumor-suppressor gene, were less likely to respond.
“This novel treatment appears promising for one of the most common and difficult-to-treat forms of lung cancer.”
Professor. David E. Gerber
Side effects and implications
Most patients experienced side effects such as nausea, fatigue, diarrhea and neutropenia (a drop in white blood cells). Despite these effects, the combination therapy showed potential for improved outcomes in advanced NSCLC. Preliminary data also suggested that selinexor may have anti-tumor activity independently of chemotherapy, warranting further investigation in future trials.
Expanding applications
These results highlight selinexor’s potential to treat NSCLC and possibly other KRAS-mutated cancers. By advancing therapies that target specific genetic changes, researchers aim to improve outcomes for patients who currently have limited options.
Reference: von Itzstein MS, Burns TF, Dowell JE, et al. Phase 1/2 trial of XPO1 inhibitor selinexor plus docetaxel in previously treated, advanced KRAS mutant non-small cell lung cancer. Clin Can Res. 2024. doi: 10.1158/1078-0432.CCR-24-1722
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