In the NADIM trial, neoadjuvant chemotherapy combined with nivolumab was successful in treating resectable non-small-cell lung cancer (NSCLC). The investigation of the circulating tumor DNA (ctDNA) and 3-year overall survival (OS) had not been published.

Patients with stage IIIA NSCLC who were considered to be surgically treatable participated in this open-label, multicenter, single-arm, phase II trial and received adjuvant nivolumab monotherapy for 1 year after receiving 3 cycles of neoadjuvant paclitaxel (200 mg/m2 once daily) and carboplatin (area under curve 6) plus nivolumab (360 mg) on day 1 of each 21-day cycle (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analyses were the trial’s secondary goals.

The intention-to-treat population’s OS at 36 months was 81.9% (95% CI, 66.8 to 90.6), but the per-protocol population’s OS increased to 91.0% (95% CI, 74.2 to 97.0). Neither the number of tumor mutations nor the staining for programmed cell death ligand-1 was an indicator of survival. On the other hand, OS and progression-free survival were both significantly enhanced by reduced pretreatment ctDNA levels (hazard ratio [HR], 0.20; 95% CI, 0.06 to 0.63; and HR, 0.07; 0.01 to 0.39, respectively). The RECIST v1.1 criteria for clinical responses did not predict survival results. However, following neoadjuvant therapy, undetectable ctDNA levels were substantially linked to both progression-free survival and OS (HR, 0.26; 95% CI, 0.07 to 0.93; and HR, 0.04; 0.00 to 0.55, respectively). Compared to RECIST criteria (0.72), the C-index to predict OS for ctDNA levels following neoadjuvant therapy (0.82) performed better.

Three-year OS data confirmed the effectiveness of neoadjuvant chemotherapy with nivolumab in resectable NSCLC. In terms of predicting survival, ctDNA levels exceeded radiologic evaluations and were substantially linked with OS.