Neoadjuvant Nivolumab and Platinum-Doublet Chemotherapy for Resectable NSCLC: CheckMate 816

Treatment outcomes for patients with resectable non–small-cell lung cancer (NSCLC) have been inconsistent. Approximately 20% to 25% of patients with NSCLC present with resectable disease, but 30% to 55% of patients experience disease recurrence following curative surgery.¹ In addition, the benefit of neoadjuvant chemotherapy compared with surgery alone is modest.¹

Nivolumab, a fully human anti–PD-1 antibody, has been shown to induce an anticancer immune response by activating antitumor T-cells.¹ Furthermore, chemotherapy was shown to induce antitumor immunity through direct or indirect immune-system activation. Accordingly, it was hypothesized that the combination of immune checkpoint inhibitors and chemotherapy could improve efficacy.¹

CheckMate 816 is a randomized phase 3 study that investigated the efficacy of neoadjuvant nivolumab plus platinum doublet chemotherapy for patients with resectable NSCLC. The study included patients with stage IB (≥4 cm) to IIIA (per AJCC Cancer Staging Manual, 7th ed) resectable NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and no known EGFR/ALK alterations. Patients were randomly assigned to receive nivolumab (360 mg) plus chemotherapy every 3 weeks (n = 179) or chemotherapy every 3 weeks for 3 cycles (n = 179). The primary end points were event-free survival (EFS) and pathologic complete response (pCR), assessed by a blinded independent review.^1,2

Patients treated with nivolumab plus chemotherapy achieved a statistically significant improvement in pCR rate compared with those treated with chemotherapy alone (24% vs 2%, respectively; odds ratio, 13.94; 99% confidence interval [CI], 3.49-55.75; P <.001).¹ The observed pCR benefit was achieved among all key subgroups, including disease stages, histologies, and PD-L1 expression levels. It is important to note that neoadjuvant nivolumab plus chemotherapy had no impact on the feasibility of curative surgery and did not result in an increased incidence of surgical complications or adverse events (AEs) compared with chemotherapy alone.¹

At a median follow-up of 29.5 months, neoadjuvant nivolumab plus chemotherapy significantly improved EFS compared with chemotherapy alone (31.6 months; 95% CI, 30.2-not reached [NR] vs 20.8 months; 95% CI, 14.0-26.7; hazard ratio [HR], 0.63; 97.38% CI, 0.43-0.91; P = .005).¹ The 2-year EFS rates were 63.8% versus 45.3%.1 In the pooled patient population, EFS was improved in patients with pCR compared with those without (median, NR vs 21.1 months; HR, 0.11; 95% CI, 0.04-0.29).²

The incidence of grade 3 to 4 treatment-related AEs was similar for both arms (33.5% vs 36.9%), and surgery-related AEs were also similar (11.4% vs 14.8%).

The researchers concluded that neoadjuvant nivolumab plus chemotherapy resulted in clinically meaningful improvement in EFS and pCR compared with chemotherapy alone. These findings established nivolumab plus chemotherapy as a potential new neoadjuvant treatment option for patients with stage IB to IIIA resectable NSCLC.

References

1. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386:1973-1985.
2. Girard N, Spicer J, Provencio M, et al. Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as neoadjuvant treatment for resectable (IB-IIIA) non-small cell lung cancer (NSCLC): event-free survival (EFS) results from the phase 3 CheckMate 816 trial. Presented at: 2022 American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract CT012.