Perioperative Nivolumab and Chemotherapy in Stage III NSCLC

Approximately 20% of patients with non–small-cell lung cancer (NSCLC) have stage III disease. Although therapeutic intent is curative for patients with locally advanced disease, historically, treatment outcomes have been poor, and there is lack of consensus on the most appropriate management.

In the industry-sponsored, open-label, multicenter, phase 2 NADIM II trial, 86 treatment-naive patients with resectable stage IIIA or IIIB NSCLC were randomized 2:1 to receive either neoadjuvant nivolumab and paclitaxel plus carboplatin (experimental group) or paclitaxel plus carboplatin alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant nivolumab for 6 months.

Pathologic complete response (pCR), the primary endpoint, occurred in 37% of patients in the experimental group compared with 7% in the control group (relative risk, 5.34; 95% CI 1.34–21.23; P=0.02). Progression-free survival at 24 months was 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25–0.88).

During neoadjuvant treatment, grade 3 or 4 adverse events occurred in 19% of patients in the experimental group compared with 10% in the control group, most commonly febrile neutropenia (5%) and diarrhea (4%). A higher percentage of patients in the experimental group underwent surgery (93% vs. 69%); there were no delays in surgery due to adverse events. All patients who attained pCR were free from progression at the time of data cutoff.