Neoadjuvant nivolumab plus chemotherapy improves event-free survival (EFS), compared with chemotherapy alone, in patients with resectable non-small cell lung cancer (NSCLC), according to results of the CheckMate 816 trial.

Nivolumab prolonged EFS by nearly 11 months and improved the pathologic complete response (pCR) rate more than 10-fold. There was a trend toward improved overall survival (OS) with nivolumab as well. 

“CheckMate 816 is the first phase 3 study with a neoadjuvant immunotherapy-based combination for resectable NSCLC to show improved event-free survival and pCR, along with promising overall survival results,” said Nicolas Girard, MD, PhD, of Institut du Thorax Curie-Montsouris in Paris.


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“These results support neoadjuvant nivolumab in combination with chemotherapy as a new standard of care for patients with resectable non-small cell lung cancer,” he added.

Dr Girard presented these results at the AACR Annual Meeting 2022.1 The findings were published simultaneously in The New England Journal of Medicine.2

The phase 3 CheckMate 816 trial (ClinicalTrials.gov Identifier: NCT02998528) enrolled 358 patients with stage IB-IIIA NSCLC. They were randomly assigned to receive neoadjuvant nivolumab plus chemotherapy (n=179) or chemotherapy alone (n=179). Baseline characteristics were well balanced between the treatment arms. 

All patients received chemotherapy every 3 weeks for 3 cycles. Patients in the nivolumab arm also received 360 mg of nivolumab every 3 weeks. Surgery was performed within 6 weeks of neoadjuvant treatment completion. Patients could receive optional adjuvant chemotherapy, with or without radiotherapy.

Results: Efficacy and Safety

The median follow-up was 29.5 months. The pCR rate was 24.0% in the nivolumab arm and 2.2% in the chemotherapy-alone arm. 

The median EFS was 31.6 months with nivolumab and 20.8 months with chemotherapy alone (hazard ratio [HR], 0.63; 97.38% CI, 0.43-0.91; P =.0052). The 2-year EFS rate was 64% and 45%, respectively. 

EFS was improved with nivolumab across nearly all patient subgroups, Dr Girard noted.

In patients with stage IIIA disease, the median EFS was 31.6 months in nivolumab arm and 15.7 months with chemotherapy alone (HR, 0.54; 95% CI, 0.37-0.80). In patients with stage IB-IIA NSCLC, there was a trend toward improvement with nivolumab, but the median EFS was not reached in either arm (HR, 0.87; 95% CI, 0.48-1.56). 

The magnitude of EFS benefit with nivolumab increased with increasing PD-L1 expression. The EFS benefit was greatest in patients with PD-L1 expression of 50% or higher (HR, 0.24; 95% CI, 0.10-0.61), followed by patients with PD-L1 expression of 1%-49% (HR, 0.58; 95% CI, 0.30-1.12) and patients with PD-L1 expression below 1% (HR, 0.85; 95% CI, 0.54-1.32). 

The researchers also observed an EFS improvement with nivolumab in both squamous (HR, 0.77; 95% CI, 0.49-1.22) and non-squamous (HR, 0.50; 95% CI, 0.32-0.79) NSCLC. 

Although the OS data are not yet mature, a preliminary OS analysis showed a trend toward improvement with nivolumab (HR, 0.57; 99.67%, 0.30-1.07; P =.0079). 

Grade 3-4 treatment-related adverse events (TRAEs) occurred in 34% of patients in the nivolumab arm and 37% of those in the chemotherapy-alone arm. TRAEs leading to treatment discontinuation occurred in 6% and 3%, respectively. There were 2 fatal TRAES in the chemotherapy-alone arm and none in the nivolumab arm. 

Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

References

1. 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 AACR 2022; April 8-13, 2022. Abstract CT012.

2. Forde P, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. Published online April 11, 2022. doi:10.1056/NEJMoa2202170

This article originally appeared on Cancer Therapy Advisor