1. Patients with resectable non-small cell lung cancer (NSCLC) receiving neoadjuvant nivolumab in addition to platinum-based chemotherapy demonstrated longer survival and treatment response after resection compared to patients only receiving chemotherapy.
2. Nivolumab treatment was not associated with any additional adverse events and did not impact the feasibility of surgical resection.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Nivolumab is an anti-programmed death 1 (PD-1) antibody aimed to restore anti-tumor immune responses. In patients with resectable early-stage non-small cell lung cancer (NSCLC), neoadjuvant treatment with Nivolumab prior to surgery showed promise in improving complete responses to treatment and survival outcomes. In this phase 3 clinical trial named CheckMate 816, the primary objective was to evaluate improvements in event-free survival and pathological complete response in patients with resectable NSCLC by neoadjuvant nivolumab. Selected patients were randomized in a 1:1 ratio to either receive three cycles of nivolumab plus platinum-based chemotherapy, or chemotherapy alone prior to surgical resection. The results of this study found that patients receiving nivolumab demonstrated significantly increased event-free survival and proportion of pathological complete response. Other secondary measures of overall survival, time to death or metastases, and radiographic downstaging also favored the group receiving nivolumab. More patients in receiving nivolumab successfully underwent surgical resection. Incidence rates of severe adverse events were similar between both groups. Taken together, this study supports the neoadjuvant use of nivolumab in patients with resectable NSCLC to improve survival and response to treatment. As a result, neoadjuvant nivolumab plus chemotherapy has been approved for clinical use in the United States in this patient population.
In-Depth [randomized controlled trial]: In this phase 3, open-label, international, multicenter randomized control trial named CheckMate 816, 358 patients with early-stage (IB – IIIA) non-small cell lung cancer (NSCLC) eligible for surgical resection were randomized in a 1:1 ratio to receive either 360 mg nivolumab and platinum-doublet chemotherapy, or chemotherapy alone for 3 cycles for completion 6 weeks prior to planned surgery. Patients were followed for the primary outcome of event-free survival, which was the time from randomization to any progression of disease or death, which was statistically compared using the stratified log-rank test. The other primary endpoint was pathological complete response, which described no viable residual tumor cells from primary tumor biopsy samples or associated lymph nodes, statistically compared using a Cochran-Mantel-Haenszel test. Secondary endpoints assessed any major pathological response, time to death or distant metastases, and overall survival. Across the cohort, 83.2% of patients receiving nivolumab-plus-chemotherapy underwent surgery, compared to 75.4% in the chemotherapy-only group. Patients receiving nivolumab had a significantly shorter median event-free survival of 31.6 months compared to 20.8 months in their chemotherapy counterparts (hazard ratio [HR], 0.63; 97.38% confidence interval [CI], 0.43-0.91; P=0.005). The nivolumab-plus-chemotherapy group also had a significantly greater proportion of patients who complete pathological response at 24% vs. 2.2% (odds ratio [OR], 13.94, 99% CI, 3.49 – 55.75; P<0.001). These trends held true for other subgroup analyses. However, no significant differences in overall survival were observed between groups in the first interim analysis which may require a longer follow-up period. Finally, the incidence of severe adverse events (grade 3 or 4) was statistically similar between both groups. Overall, this study provides evidence to support the use of neoadjuvant nivolumab in addition to platinum-doublet chemotherapy in patients with resectable NSCLC to improve downstream outcomes of event-free survival and complete pathological response.
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