In analyses from a Spanish phase II trial (NADIM) reported in the Journal of Clinical Oncology, Provencio et al found a high rate of 3-year overall survival in patients with operable stage IIIA non–small cell lung cancer (NSCLC) who received neoadjuvant nivolumab plus chemotherapy. Survival was associated with baseline and post–neoadjuvant therapy circulating tumor DNA (ctDNA) levels.
The primary analysis of the trial showed a 24-month progression-free survival rate of 77.1% and a pathologic complete response rate of 63.4%. Three-year overall survival and ctDNA analyses were secondary objectives of the trial.
In the multicenter trial, 46 patients (intent-to-treat [ITT] population) received paclitaxel at 200 mg/m2 once daily and carboplatin at area under the curve = 6 plus nivolumab at 360 mg once on day 1 of each 21-day cycle for three cycles, followed by adjuvant nivolumab monotherapy for 1 year at 240 mg once every 2 weeks for 4 months, and then at 480 mg once every 4 weeks for 8 months. The per-protocol population consisted of 37 patients who underwent resection and received adjuvant nivolumab.
The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year overall survival. ctDNA levels were significantly associated with overall survival and outperformed radiologic assessments in the prediction of survival.— Provencio et al
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Overall survival at 36 months was 81.9% (95% confidence interval [CI] = 66.8%–90.6%) in the ITT population and 91.0% (95% CI = 74.2%–97.0%) in the per-protocol population.
In the ITT population, patients with low ctDNA levels (< 1% mutant allele fraction) at baseline had significantly improved progression-free survival (adjusted hazard ratio [HR] = 0.20, P = .006) and overall survival (adjusted HR = 0.07, P = .002) vs patients with higher ctDNA levels. No significant associations were observed for baseline tumor mutation burden (HRs for ≥ 10 mut/Mb = 1.67, P = .474, for progression-free survival and 2.13, P = .399, for overall survival) or for tumor PD-L1 expression ≥ 1% (HRs = 0.64, P = .508, for progression-free survival and 0.35, P = .252, for overall survival.
Undetectable ctDNA after neoadjuvant treatment was significantly associated with improved progression-free survival (HR = 0.26, P = .038) and overall survival (HR = 0.04, P = .015). No association was observed for clinical objective response according to Response Evaluation Criteria in Solid Tumors version 1.1 criteria (HRs = 0.79, P = .698, for progression-free survival and 0.87, P = .848, for overall survival). The C-index values were 0.63 for undetectable ctDNA vs 0.62 for clinical response for progression-free survival and 0.82 vs 0.72 for overall survival.
The investigators concluded, “The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year overall survival. ctDNA levels were significantly associated with overall survival and outperformed radiologic assessments in the prediction of survival.”
Mariano Provencio, MD, PhD, of the Medical Oncology Department, Hospital Puerta de Hierro, Madrid, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the European Union Horizon 2020 Research and Innovation program, Bristol Myers Squibb, and others. For full disclosures of the study authors, visit ascopubs.org.
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