Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA NSCLC (NADIM Phase II trial)
鈥 An ASCO Reading Room selection
August 19, 2022This Reading Room is a collaboration between 名媛直播庐 and:
Purpose
Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non–small-cell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: ). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported.
Methods
This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (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 analysis were secondary objectives of the trial.
Results
OS at 36 months was 81.9% (95% CI 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR] 0.20, 95% CI 0.06 to 0.63, and HR 0.07, 95% CI 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR 0.26, 95% CI 0.07 to 0.93, and HR 0.04, 95% CI 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72).
Conclusion
The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival.
Read an interview about the study here and expert commentary about the clinical implications here.
Read the full article
Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA NSCLC (NADIM Phase II trial)
Primary Source
Journal of Clinical Oncology
Source Reference: