In the Spanish phase II NADIM II trial reported in The New England Journal of Medicine, Mariano Provencio, MD, PhD, and colleagues found that the addition of nivolumab to platinum-based chemotherapy improved pathologic complete response (pCR) rates among patients with resectable stage IIIA or IIIB non–small cell lung cancer (NSCLC).
Mariano Provencio, MD, PhD
Study Details
In the open-label multicenter trial, 86 previously untreated patients were randomly assigned 2:1 between June 2019 and February 2021 to receive neoadjuvant nivolumab at 360 mg plus paclitaxel at 200 mg/m2 and carboplatin at area under the curve = 5 every 21 days for three cycles (n = 57) or paclitaxel plus carboplatin at the same dose/schedule (n = 29). Patients in the nivolumab group who underwent R0 resection received adjuvant nivolumab at 480 mg every 4 weeks for 6 months. The primary endpoint was pCR rate.
pCR Rate
pCR was observed in 21 (37%, 95% confidence interval [CI] = 24%–51%) of 57 patients in the nivolumab group vs 2 (7%, 95% CI = 1%–23%) of 29 patients in the control group (relative risk [RR] = 5.34, 95% CI = 1.34–21.23, P = .02). Surgery was performed in 93% vs 69% of patients (RR = 1.35, 95% CI = 1.05–1.74). R0 resection was achieved in 50 (94%) vs 17 (85%) of patients.
Median follow-up was 26.1 months (interquartile range = 17.4–30.9 months). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% (95% CI = 55.8%–81.0%) in the nivolumab group vs 40.9% (95% CI = 26.2%–63.6%) in the control group (hazard ratio [HR] = 0.47, 95% CI = 0.25–0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% (95% CI = 75.9%–95.2%) in the nivolumab group vs 63.6% (95% CI = 47.8%–84.6%) in the control group (HR = 0.43, 95% CI = 0.19–0.98).
KEY POINTS
- The addition of neoadjuvant nivolumab to platinum-based chemotherapy significantly improved pCR rate.
- The addition of neoadjuvant and adjuvant nivolumab to neoadjuvant chemotherapy was associated with improved progression-free and overall survival.
Adverse Events
During neoadjuvant treatment, grade 3 or 4 adverse events occurred in 19% of patients in the nivolumab group vs 10% of the control group, most commonly febrile neutropenia (5%) and diarrhea (4%) in the nivolumab group. Treatment-related adverse events led to discontinuation of neoadjuvant treatment in four patients in the nivolumab group vs one in the control group. No delays in surgery occurred due to adverse events. Grade 3 or 4 adverse events occurred in 2 of 44 patients (5%) in the nivolumab group during adjuvant nivolumab treatment.
The investigators concluded, “In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pCR and longer survival than chemotherapy alone.”
Dr. Provencio, of the Medical Oncology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Bristol Myers Squibb and others. For full disclosures of the study authors, visit nejm.org.
