Stage IIIA/B NSCLC: Perioperative nivolumab plus chemo improves pCR, survival vs neoadjuvant chemo

Perioperative nivolumab plus platinum-based chemotherapy improves pathological complete response (pCR) rate and survival outcomes vs neoadjuvant platinum-based chemotherapy alone in patients with resectable stage IIIA/B non-small-cell lung cancer (NSCLC), results of the NADIM II trial have shown.

In the open-label, multicentre, phase II trial, 86 patients with previously untreated, resectable, stage IIIA/B NSCLC with nodal stage of N0–2 and no known sensitizing EGFR mutations or ALK rearrangements were randomized to receive neoadjuvant nivolumab (360 mg) plus chemotherapy with paclitaxel (200 mg/m²) and carboplatin (area under curve, 5 mg/mL/min) (n=57; median age, 65 years; male, 63 percent; median tumour size, 50 mm; N2 stage, 72 percent), or chemotherapy alone (n=29; median age, 63 years; male, 55 percent; median tumour size, 52 mm; N2 stage, 55 percent) Q3W for 3 cycles, followed by surgery within 4 weeks. Patients with R0 resection after neoadjuvant nivolumab plus chemotherapy further received adjuvant nivolumab 480 mg Q4W for 6 months. [N Engl J Med 2023;389:504-513]

The primary endpoint of pCR rate was significantly higher in the nivolumab plus chemotherapy vs chemotherapy alone group (37 percent vs 7 percent; relative risk [RR], 5.34; 95 percent confidence interval [CI], 1.34–21.23; p=0.02) in the intention-to-treat population, with improvement across all subgroups.

At a median follow-up of 26.1 months (data maturity at 24 months, 95.2 percent), progression-free survival (PFS) was improved with nivolumab plus chemotherapy vs chemotherapy alone (median, not reached [NR] vs 15.4 months; hazard ratio [HR], 0.47; 95 percent CI, 0.25–0.88). Estimated PFS rate at 24 months was 67.2 percent vs 40.9 percent.

Median overall survival (OS) was NR in both groups, while estimated OS rate at 24 months was 85.0 percent with nivolumab plus chemotherapy vs 63.6 percent with chemotherapy alone (HR, 0.43; 95 percent of CI, 0.19–0.98).

Notably, all patients achieving pCR were alive and free from disease progression or recurrence. Survival outcomes were not worse in patients with N2 disease than those with N0 or N1 disease.

Grade 3/4 adverse events (AEs) occurred in 19 percent (n=11) vs 10 percent (n=3) of patients treated with nivolumab plus chemotherapy vs chemotherapy alone. No delays in surgery were due to AEs.

Surgery was performed in 93 percent (n=53) vs 69 percent (n=20) of patients in the nivolumab plus chemotherapy vs chemotherapy alone group (RR, 1.35; 95 percent CI, 1.05–1.74). R0 resection was achieved in 94 percent (n=50) vs 85 percent (n=17) of patients, while nodal downstaging was achieved in 72 percent (n=38) vs 40 percent (n=8) of patients. Only one death due to surgical complication was reported in the nivolumab group 13 days after right pneumonectomy.

“Neoadjuvant chemoimmunotherapy [ie, nivolumab plus chemotherapy] has been shown to be safe, without impacting surgical feasibility and outcomes [in resectable NSCLC],” the researchers noted. [J Clin Oncol 2022;40:2924-2933; N Engl J Med 2022;386:1973-1985; Eur J Cardiothorac Surg 2021;60:81-88; J Clin Oncol 2021;39(Suppl):8503]

Among patients with R0 resection after neoadjuvant nivolumab plus chemotherapy, 84 percent (n=42) received ≥1 cycle (median, 4.2 cycles) of adjuvant nivolumab, and 66 percent (n=33) completed adjuvant nivolumab. Grade 3/4 AEs occurred in 5 percent (n=2/44) of patients. [N Engl J Med 2023;389:504-513]

“Upon R0 resection, patients who completed adjuvant nivolumab achieved better survival outcomes [including OS and PFS] vs those who did not. These results suggest a positive effect of this treatment approach [ie, use of adjuvant nivolumab in patients with completely resected stage IIIA/B NSCLC],” commented the researchers.