As reported in The New England Journal of Medicine by Tina Cascone, MD, PhD, and colleagues, interim analysis in the phase III CheckMate 77T trial has shown that the addition of perioperative nivolumab to neoadjuvant chemotherapy improved event-free survival in patients with resectable non–small cell lung cancer (NSCLC).

Tina Cascone, MD, PhD

Study Details

The multinational double-blind trial included 461 patients with resectable stage IIA to IIIB disease. They were randomly assigned between November 2019 and April 2022 to receive neoadjuvant nivolumab at 360 mg plus platinum-doublet chemotherapy (nivolumab group, n = 229) or neoadjuvant chemotherapy plus placebo (chemotherapy group, n = 232) every 3 weeks for four cycles, followed by surgery and adjuvant nivolumab at 480 mg or placebo every 4 weeks for 1 year.  

Chemotherapy was cisplatin-based in 24% vs 18% of patients and carboplatin-based in 73% vs 78%. The primary outcome measure was event-free survival on blinded independent review, with events defined as disease progression or recurrence, abandoned surgery, or death.

Event-Free Survival Results

At the prespecified interim analysis, with a median follow-up of 25.4 months (range = 15.7–44.2 months), 18-month event-free survival was 70.2% (95% confidence interval [CI] = 63.4%–76.0%) in the nivolumab group and 50.0% (95% CI = 42.9%–56.7%) in the chemotherapy group (hazard ratio = 0.58, 97.36% CI = 0.42–0.81, P < .001).  Median event-free survival was not reached (95% CI = 28.9 months to not reached) vs 18.4 months (95% CI = 13.6–28.1 months). Rates at 6 and 12 months were 84.6% vs 79.9% and 73.4% vs 59.2%, respectively.

For stratification factors, hazard ratios for event-free survival for the nivolumab group vs chemotherapy group were:

• 73 (95% CI = 0.47–1.15) among 186 patients with tumor PD-L1 expression < 1% and 0.52 (95% CI = 0.35–0.78) among 256 patients with expression ≥ 1%
• 81 (95% CI = 0.46–1.43) among 162 patients with stage II disease and 0.51 (95% CI = 0.36–0.72) among 297 with stage III disease
• 46 (95% CI = 0.30–0.72) among 234 patients with squamous histology and 0.72 (95% CI = 0.49–1.07) among 227 with nonsquamous histology.

Pathologic complete response was achieved in 25.3% of patients in the nivolumab group vs 4.7% of patients in the chemotherapy group (odds ratio [OR] = 6.64, 95% CI = 3.40–12.97); major pathologic response occurred in 35.4% vs 12.1% (OR = 4.01, 95% CI = 2.48–6.49).

Adverse Events

Grade 3 or 4 treatment-related adverse events occurred in 32.5% of patients in the nivolumab group vs 25.2% of those in the chemotherapy group; the most common event was decreased neutrophils in both groups (10.1% vs 6.5%). Treatment-related serious adverse events occurred in 19.3% vs 13.6% of patients, and treatment-related adverse events led to treatment discontinuation in 19.3% vs 7.4%.

The most common immune-mediated adverse event was hypothyroidism/thyroiditis, observed in 11.0% vs 1.7% of patients. Fatal adverse events considered related to treatment occurred in two patients in the nivolumab group (pneumonitis in both patients) and in no patients in the chemotherapy group.

The investigators concluded, “Perioperative treatment with nivolumab resulted in significantly longer event-free survival than chemotherapy in patients with resectable NSCLC. No new safety signals were observed.”

Tina Cascone, MD, PhD, of The Uni­versity of Texas MD Anderson Cancer Center, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit nejm.org.