2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.40 Wild Type TP53 is Associated with Therapeutic Activity of Nuclear Export Inhibition in KRAS Mutant Non-Small Cell Lung Cancer

PP01.40 Wild Type TP53 is Associated with Therapeutic Activity of Nuclear Export Inhibition in KRAS Mutant Non-Small Cell Lung Cancer

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This study explores the efficacy of selinexor, a nuclear export inhibitor, combined with docetaxel in treating KRAS mutant non-small cell lung cancer (NSCLC), particularly focusing on patients with varying TP53 mutation status. The trial involved 40 patients undergoing a dose escalation of selinexor, followed by docetaxel, aiming to assess safety and therapeutic outcomes—progression-free survival (PFS) and overall survival (OS). Comprehensive sequencing data were available for 26 patients, allowing for detailed mutation analysis.<br /><br />Key findings include:<br /><br />- The maximum tolerated doses were established as selinexor 60 mg weekly and docetaxel 75 mg/m² every three weeks.<br />- Adverse events were largely hematological and gastrointestinal.<br />- Patients with wild-type (WT) TP53 showed notably better outcomes than those with TP53 mutations. Median PFS was 6 months for WT TP53 compared to 1.8 months for mutant TP53 (p = 0.006), and median OS was 15.4 months for WT TP53 versus 5.8 months for mutant TP53 (p = 0.03).<br />- Patients with a specific KRAS G12C mutation had a median PFS of 4.0 months, similar to those with non-G12C mutations (4.1 months).<br />- The study noted significant changes in serum LDH levels with treatment, decreasing by 48 U/L in TP53 WT patients, while increasing by 51 U/L in those with TP53 mutations (p = 0.06).<br /><br />These results suggest that selinexor, combined with docetaxel, is effective and well-tolerated, particularly in the TP53 WT population. The data indicate that selinexor alone might also be promising, warranting further investigation. The study underscores the importance of TP53 status in predicting treatment outcomes in KRAS mutant NSCLC.

Asset Subtitle

Mitchell von Itzstein

Keywords

selinexor

docetaxel

KRAS mutant NSCLC

TP53 mutation

progression-free survival

overall survival

maximum tolerated dose

adverse events

serum LDH levels

mutation analysis