The addition of neoadjuvant nivolumab to chemotherapy delivers improved event-free survival and more patients with a pathological complete response than chemotherapy alone in resectable non-small cell lung cancer (NSCLC), new findings show.
The CheckMate 816 study, published in the NEJM and presented at the 2022 AACR Annual Meeting, randomised 358 patients with stage IB to IIIA disease to either neoadjuvant nivolumab plus three cycles of platinum-doublet chemotherapy or chemotherapy alone.
With a minimum follow-up of 21 months, the median event-free survival was 31.6 months with nivolumab plus chemotherapy compared to 20.8 months with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005).
“At 1 year, the estimated percentage of patients surviving without disease progression or disease recurrence was 76.1% with nivolumab plus chemotherapy and 63.4% with chemotherapy alone; at 2 years, the corresponding values were 63.8% and 45.3%,” the study authors said.
The proportion of patients with a pathological complete response was 24.0% with nivolumab plus chemotherapy compared to 2.2% with chemotherapy alone (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001).
“A benefit with nivolumab plus chemotherapy with respect to pathological complete response was observed across all key subgroups, including those based on disease stage, tumor PD-L1 expression level, and histologic type.”
“Other key outcomes, including overall survival, time to death or distant metastases, major pathological response, event-free survival 2, objective response, and radiographic downstaging, also favored nivolumab plus chemotherapy.”
The researchers, led by Associate Professor Patrick Forde from John Hopkins Medicine, said treatment with nivolumab plus chemotherapy did not result in a higher incidence or greater severity of adverse events than chemotherapy alone.
As well nivolumab did not increase surgery-related adverse events or impede the feasibility of surgery.
“An exploratory analysis involving a subgroup of patients suggested that ctDNA clearance before surgery was more common among patients receiving nivolumab plus chemotherapy than among those receiving chemotherapy alone.”
They said ctDNA clearance during neoadjuvant therapy may be an early predictor of favorable outcomes but additional research was warranted.
“CheckMate 816 builds on robust findings for nivolumab-based regimens in advanced NSCLC and a strong biologic rationale for use in resectable NSCLC, especially in the neoadjuvant context,” the researchers concluded.
An accompanying editorial in the NEJM said broad implementation of neoadjuvant therapy was expected to herald a new era for lung cancer.
“Results from this trial are expected to be practice changing, as evidenced by the FDA approval of neoadjuvant nivolumab plus chemotherapy on March 4.”
However questions remained including whether adjuvant therapy was necessary for everyone and if not, how to select those patients who might benefit from those who might not.
The study was sponsored by Bristol Myers Squibb.