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.

Reference: ascopubs.org/doi/full/10.1200/JCO.21.02660