The combination of neoadjuvant nivolumab plus chemotherapy continues to demonstrate potential as a standard treatment for patients with resectable non–small cell lung cancer (NSCLC), according to data presented during the European Lung Cancer Congress 2023.1
The 3-year update from the phase III CheckMate 816 study showed statistically significant and clinically meaningful improvements in long-term event-free survival and pathologic complete response with the combination of neoadjuvant nivolumab plus chemotherapy vs chemotherapy alone in patients with resectable NSCLC. The combination therapy also demonstrated a “promising overall survival trend and a tolerable safety profile,” the study authors reported. Importantly, results of an exploratory biomarker analysis suggested the potential for more personalized treatment decisions.
Nicolas Girard, MD
“[T]here is an unmet need for biomarkers to identify patients with resectable NSCLC who may derive the highest clinical benefit from neoadjuvant or adjuvant immunotherapy,” said lead study author Nicolas Girard, MD, of the Curie Institute, Paris. “These results further support the use of nivolumab plus chemotherapy as a standard neoadjuvant treatment for patients with resectable NSCLC and highlight the potential for biomarker-guided patient selection.”
Study Methods and Key Findings
CheckMate 816 is a randomized phase III trial evaluating neoadjuvant nivolumab plus chemotherapy in patients with newly diagnosed, resectable stage IB (tumors ≥ 4 cm) to IIIA NSCLC without known driver alterations. The trial included 358 patients, who were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone for three cycles every 3 weeks. Surgery was to be performed within 6 weeks after the last dose of neoadjuvant treatment, and optional adjuvant therapies could be administered at the investigator’s discretion.
As Dr. Girard reported, the 3-year event-free survival rates showed a continued, durable, long-term event-free survival improvement with the combination of nivolumab plus chemotherapy vs chemotherapy alone. With a minimum follow-up of 32.9 months and a median follow-up of 41.4 months, the 3-year event-free survival rates were 57% in the nivolumab-plus-chemotherapy arm and 43% in the chemotherapy arm (hazard ratio [HR] = 0.68). The median event-free survival was not reached in the nivolumab-plus-chemotherapy arm and 21.1 months in the chemotherapy arm. The 3-year update also demonstrated a benefit in terms of time to distant metastasis with nivolumab plus chemotherapy vs chemotherapy alone (HR = 0.55).
Among patients who underwent surgery, fewer in the nivolu-mab-plus-chemotherapy arm had disease recurrence compared with patients who received chemotherapy alone (28% vs 42%). Fewer distant recurrences were observed with nivolumab plus chemotherapy (10% of patients) vs chemotherapy alone (22%), with a significant reduction in central nervous system recurrences (4% vs 15%).
The safety profile of neoadjuvant nivolumab plus chemotherapy was consistent with previous reports, with no additional signal of toxicity identified. The rate of treatment-related grade 3 or 4 adverse events was 36% in the experimental arm vs 38% in the chemotherapy-alone arm, said Dr. Girard.
An exploratory biomarker analysis was also conducted to identify potential predictors of treatment response. The study evaluated the four-gene inflammatory signature, which includes CD8A, STAT1, LAG3, and CD274, assessed by RNA sequencing from evaluable tumor samples at baseline. In patients who received nivolumab plus chemotherapy, higher four-gene inflammatory signature scores were associated with a pathologic complete response or a major pathologic response. This trend was also observed for improved event-free survival in patients who received nivolumab plus chemotherapy, but not in those who received chemotherapy alone.
“These findings are consistent with data from other solid cancers, such as advanced NSCLC, mesothelioma, melanoma, and gastric cancer, showing a correlation between high inflammatory scores and higher response rates or improved survival,” said Dr. Girard.
DISCLOSURE: Dr. Girard reported financial relationships with AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Janssen, Boehringer Ingelheim, AbbVie, Amgen, Eli Lilly, Grünenthal, Takeda, Owkin, and Sivan.
1. Girard N, Spicer J, Provencio M, et al: Neoadjuvant nivolumab plus platinum-doublet chemotherapy for resectable NSCLC. European Lung Cancer Congress 2023. Abstract 840. Presented March 30, 2023.
Antonio Passaro, MD, PhD
Invited discussant Antonio Passaro, MD, PhD, of the European Institute of Oncology, Milan, Italy, underscored the significant results of the landmark CheckMate 816 trial, which he said, “established a new treatment paradigm for resectable NSCLC [non–small cell lung...