Among patients with resectable non–small cell lung cancer (NSCLC), and more frequent pathological complete response in patients than chemotherapy alone.
“Our data show that three cycles of neoadjuvant nivolumab plus chemotherapy improved long-term clinical outcomes in patients with resectable stage IB-IIIA NSCLC without impeding the feasibility of surgery or increasing the incidence of adverse events as compared with chemotherapy alone,” wrote the investigators, who were led by Patrick M. Forde, MB, BCh, Johns Hopkins Kimmel Cancer Center, Baltimore. The study was published online in the New England Journal of Medicine.
Nivolumab (Opdivo, Bristol-Myers Squibb), in combination with platinum-doublet chemotherapy, was approved in March by the Food and Drug Administration as a treatment for adults with early-stage, resectable NSCLC. It is the first approval of a neoadjuvant therapy for this patient population. The results of the study, called CheckMate 816, formed the basis of the approval.
About one in four NSCLC patients have resectable disease at diagnosis, but their mortality rate is 30%-55% even after surgery. Neoadjuvant chemotherapy improves survival in this group, but 5-year recurrence rates improve by just 5%-6%, and rates of pathological complete response are low.
In the neoadjuvant setting, the anti–programmed death 1 (PD-1) antibody nivolumab could reduce micrometastases and boost immune response against bulk tumor and tumor antigens. A phase 2 study published in the Journal of Thoracic Oncology showed that neoadjuvant nivolumab combined with chemotherapy conferred good 3-year overall survival (81.9%) and progression-free survival (69.6%) among patients with stage IIIA NSCLC.
Results from CheckMate 816
CheckMate 816 is an open-label, phase 3 trial in which 358 patients were randomized to a neoadjuvant course of 360 mg nivolumab and platinum-doublet chemotherapy or platinum-doublet chemotherapy alone. Treatments occurred every 3 weeks for three cycles.
Definitive surgery was performed in 83.2% of the combination group (R0, 83.2%) and 75.4% in the chemotherapy-only group (R0, 77.8%). 93.8% in the combined group and 84.7% in the chemotherapy-only group completed neoadjuvant treatment. 11.9% of the combination group and 22.2% in the chemotherapy-only group underwent adjuvant therapy. A total of 21.2% in the combination group had cancer therapy versus 43.6% of the chemotherapy-only group.
After a minimum follow-up of 21 months, the combination group had a median event-free survival of 31.6 months versus 20.8 months in the chemotherapy-only group (hazard ratio for disease progression, disease recurrence, or death, 0.63; P = .005). The interim analysis for overall survival showed a possible trend towards improved overall survival in the combination group (HR, 0.57; 99.67% confidence interval, 0.30-1.07; P = .0008).
A total of 24.0% of the combination therapy achieved a pathological complete response versus 2.2% in the chemotherapy-only group (odds ratio, 13.94; P < .001).
Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the combination group and 36.9% of the chemotherapy-only group.
The researchers noted that 63.1% of patients in the study had stage IIIA tumors, which has a poor prognosis.
There were benefits to the combination treatment across PD-1–status subgroups, but event-free survival was higher where PD-L1 expression level was 1% or more.
The study is limited by its open-label nature. It was funded by Bristol-Myers Squibb.
