In the Spanish phase II NADIM trial reported in The Lancet Oncology, Provencio et al found that the addition of nivolumab to neoadjuvant chemotherapy and the use of adjuvant nivolumab were associated with high 24-month rates of progression-free survival in patients with resectable stage IIIA non–small cell lung cancer (NSCLC).
Study Details
In the multicenter trial, 46 patients enrolled between April 2017 and August 2018 were to receive neoadjuvant treatment with paclitaxel at 200 mg/m² and carboplatin area under curve = 6 plus nivolumab at 360 mg on day 1 of each 21-day cycle for three cycles before surgical resection. Patients were then to receive adjuvant nivolumab monotherapy for 1 year at 240 mg every 2 weeks for 4 months followed by 480 mg every 4 weeks for 8 months.
The primary endpoint was progression-free survival at 24 months in the modified intent-to-treat (ITT) population (consisting of all patients who received neoadjuvant treatment) and in the per-protocol population (consisting of all patients who had tumor resection and received at least one cycle of adjuvant nivolumab).
Progression-Free Survival
At data cutoff (January 2020), median follow-up was 24 months. The modified ITT population included all 46 patients. A total of 41 patients underwent surgery; of these, 37 received one or more cycles of adjuvant nivolumab and constituted the per-protocol population.
Median progression-free survival was not reached in the ITT or per protocol populations. In the ITT population, progression-free survival was 95.7% at 12 months, 87.0% at 18 months, and 77.1% at 24 months. In the per-protocol population, progression-free survival was 100% at 12 months, 91.9% at 18 months, and 87.9% at 24 months. Of 37 patients who received adjuvant nivolumab, 33 (89%) had no evidence of disease on examination or computed tomography imaging.
In the ITT population, overall survival was 97.8% at 12 months, 93.5% at 18 months, and 89.9% at 24 months. In the per-protocol population, overall survival was 100% at 12 months, 97.3% at 18 months, and 97.3% at 24 months.
Adverse Events
Treatment-related adverse events occurred in 93% of patients during neoadjuvant treatment. Treatment-related grade ≥ 3 adverse events occurred in 30% of patients, with the most common being increased lipase (7%) and febrile neutropenia (7%). None of the adverse events during neoadjuvant treatment led to treatment discontinuation, dose reduction, surgery delay, or death. Adverse events prevented 3 (7%) of 46 patients from receiving adjuvant nivolumab, with causes consisting of hematologic toxicity in 2 and renal insufficiency in 1.
Among the 37 patients receiving adjuvant nivolumab, treatment-related grade ≥ 3 adverse events occurred in 8 patients (22%) during adjuvant therapy, with the most common being elevated serum lipase (11%) and increased serum amylase (8%). Treatment-related adverse events led to discontinuation of adjuvant nivolumab in five patients (14%). No adverse events led to death during adjuvant treatment.
The investigators concluded, “Our results support the addition of neoadjuvant nivolumab to platinum-based chemotherapy in patients with resectable stage IIIA NSCLC. Neoadjuvant chemoimmunotherapy could change the perception of locally advanced lung cancer as a potentially lethal disease to one that is curable.”
Mariano Provencio, MD, of the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb, Instituto de Salud Carlos III, and European Union’s Horizon 2020 research and innovation program. For full disclosures of the study authors, visit thelancet.com.
