Neoadjuvant Nivolumab Plus Chemotherapy Significantly Prolongs EFS Vs Chemo Alone in Resectable NSCLC

Results from the phase 3 CheckMate 816 trial show patients with resectable non¬–small cell lung cancer had improved event-free survival when treated with neoadjuvant nivolumab plus chemotherapy vs chemotherapy alone.

Treatment with neoadjuvant nivolumab (Opdivo) plus chemotherapy resulted in a longer event-free survival (EFS) vs chemotherapy alone for patients with resectable non–small cell lung cancer, based on results of the phase 3 CheckMate 816 trial (NCT02998528).

At a minimum follow-up of 21 months, the median EFS was 31.6 months (95% CI, 30.2–not reached) in the combination arm and 20.8 months (95% CI, 14.0-26.7) in the chemotherapy arm (Hazard ratio [HR], 0.63; 97.38%, 0.43-0.91; P = .005). The pathological complete response (pCR) rate was 24.0% (95% CI, 18.0%-31.0%) in the combination arm and 2.2% (95% CI, 0.6%-5.6%) in the chemotherapy arm (OR, 13.94; 99% CI, 3.49-55.75; P <.001). The exploratory analysis found those without a pCR had a median EFS of 26.6 months in the combination group and 18.4 months in the chemotherapy group (HR, 0.84; 95% CI, 0.61-1.17).

A total of 773 patients enrolled on the study and 505 were randomized and 358 were concurrently assigned to either the combination group (n = 179) or the chemotherapy alone group (n = 179). A total of 176 patients in each group received treatment. Adjuvant chemotherapy was administered in 11.9% of patients in the combination group and 22.2% in the chemotherapy group. Subsequent cancer therapy was administered to 21.2% and 43.6%, of patients respectively, and subsequent systemic therapy was given to 17.3% of patients in the combination group and 36.3% in the chemotherapy group.

Patients in the experimental arm received 360 mg of nivolumab plus platinum doublet chemotherapy or platinum doublet chemotherapy alone every 3 weeks for 3 cycles. Patients then underwent surgery within 6 weeks of treatment completion; they could also receive up to 4 cycles of adjuvant chemotherapy, radiotherapy, or both.

Definitive surgery was performed in 83.2% of patients in the combination group and 75.4% in the chemotherapy group. Surgery was canceled for 15.6% vs 20.7% of patients, with reasons for cancellation including disease progression (6.7% vs 9.5%), adverse effects (AEs; 1.1% vs 0.6%), and other reasons (7.8% vs 10.6%), in the combination and chemotherapy groups, respectively.

In total, 76.1% vs 63.4% of patients in the experimental and control groups, respectively, were estimated to have survived without progression or recurrence at 1 year. At 2 years, the rates were 63.8% vs 45.3% in each respective group. The EFS for the combination group was maintained after adjustments so patients could receive optional adjuvant therapy (HR, 0.65; 95% CI, 0.47-0.90).

The experimental arm had a higher rate of major pCR (36.9%) compared with the chemotherapy group (8.9%; OR, 5.70; 95% CI, 3.16-10.26). Investigators also observed that the depth of pathological remission in the primary tumor was greater in the combination group vs the chemotherapy group regardless of baseline disease. When response incidence was assessed according to blinded independent central review, investigators noted that incidence was higher in the combination arm vs the chemotherapy arm, with a downstaging incidence of 30.7% and 23.5%, respectively.

The median overall survival (OS) was not reached for either group (HR, 0.57; 99.67 CI, 0.30-1.07; P = .008). Additionally, at the first interim analysis, the P-value for OS did not cross the boundary for statistical significance (P = .0033). The HR for death or distant metastases between the 2 arms was 0.53 (95% CI, 0.36-0.77), and the HR for disease recurrence, progression after the next line of therapy, or death was 0.54 (95% CI, 0.37-0.80).

Any grade AEs occurred in 92.6% vs 97.2% of patients in the combination and chemotherapy groups, respectively, and grade 3/4 AEs occurring in 33.5% vs 36.9%. The most common grade 3 or 4 AEs were neutropenia (8.5% vs 11.9%) and decreased neutrophil count (7.4% vs 10.8%) in the combination and chemotherapy groups, respectively.

A total of 10.2% of patients in the combination group and 9.7% in the chemotherapy group had treatment-related AEs of any grade that led to discontinuation Moreover, 8.5% of patients in the experimental group had any grade rash and 1.1% experienced grade 1 or 2 pneumonitis In the chemotherapy group, 3 treatment-related deaths occurred.

Two patients experienced grade 5 surgery-related AEs in the combination groups and were unrelated to treatment. AEs included pulmonary embolism and aortic rupture.


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