Data from Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial

• DOI: 10.1158/1078-0432.c.7181313.v1
• Publication Date: 2024-04-15T07:22:18Z
• Authors: Hyung-Joo Oh; Suk-Chul Bae; In-Jae Oh; Cheol-Kyu Park; Kyoung-Mi Jung; Da-Mi Kim; Jung-Won Lee; Chang Kyun Kang; Il Yeong Park; Young-Chul Kim

<div>AbstractPurpose:<p><i>RUNX3</i> is a tumor suppressor gene, which inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, sirtuin inhibitor, has demonstrated potential re-activating epigenetically silenced <i>RUNX3</i> cancer cells. This study assessed the therapeutic benefits combining nicotinamide with first-generation EGFR–tyrosine kinase inhibitors (TKI) for patients stage IV carrying <i>EGFR</i> mutations.</p>Patients and Methods:<p>We impact on carcinogen-induced adenocarcinomas mice observed that increased levels inhibited growth. Subsequently, 110 consecutive who had mutations were recruited: 70 females (63.6%) 84 never-smokers (76.4%). The randomly assigned to receive either (1 g/day, <i>n</i> = 55) or placebo (<i>n</i> 55). primary secondary endpoints progression-free survival (PFS) overall (OS), respectively.</p>Results:<p>After median follow-up 54.3 months, group exhibited PFS 12.7 months [95% confidence interval (CI), 10.4–18.3], while 10.9 (9.0–13.2; <i>P</i> 0.2). OS was similar two groups (31.0 vs. 29.4 placebo; Notably, subgroup analyses revealed significant reduction mortality risk (<i>P</i> 0.01) 0.03) treated nicotinamide.</p>Conclusions:<p>The addition EGFR-TKIs improvements OS, notable female those never smoked (ClinicalTrials.gov Identifier: NCT02416739).</p></div>