Nivolumab plus chemotherapy as a neoadjuvant treatment improves event-free survival (EFS) among patients with resectable non-small cell lung cancer (NSCLC) compared with chemotherapy alone, according to phase 3 trial data. The findings from the CHECKMATE-816 study (Abstract CT012) were presented on April 11 at the AACR Annual Meeting 2022 in New Orleans and published in The New England Journal of Medicine.
On March 4, 2002, the U.S. Food and Drug Administration (FDA) approved nivolumab with platinum-doublet chemotherapy for the treatment of adult patients with resectable NSCLC based on these findings. The move marks the first FDA approval for neoadjuvant therapy for early-stage NSCLC and is a significant step for treatment in this setting, said David Carbone, MD, PhD, who served as the discussant at the AACR session.
“Progress in lung cancer typically happens by slow progress punctuated by quantum leaps,” said Dr. Carbone, who is also the director of the Thoracic Oncology Center at The Ohio State University Comprehensive Cancer Center in Columbus.
“Combining immuno-oncology with surgery I think is a new standard of care and will almost certainly improve overall survival in early-stage disease for the first time in decades in my entire career,” Dr. Carbone said.
About 20 to 25% of patients who are diagnosed with NSCLC have resectable disease, but roughly half of those who undergo potentially curative surgery experience recurrence that can ultimately lead to death. Neoadjuvant chemotherapy can be administered before the surgery, but the difference in recurrence-free and overall survival has typically been small, between only 5% and 6%.
Phase 2 studies suggested that neoadjuvant nivolumab alone or in combination with chemotherapy could improve outcomes among patients with resectable NSCLC.
Nivolumab is an anti–programmed death 1 (PD-1) antibody that restores the function of existing antitumor T cells, while chemotherapy improves the antitumor immunity caused by immune-system activation. The FDA has also approved nivolumab, ipilimumab, and chemotherapy for the first-line treatment in metastatic NSCLC patients with no EGFR or ALK genomic tumor aberrations.
In the CHECKMATE-816 trial, 179 patients were randomly assigned to receive nivolumab plus chemotherapy, and 179 patients were given chemotherapy alone. The primary endpoints were pathologic complete response (pCR), defined as a lack of signs of cancer in tissue samples removed after radiation treatment or chemotherapy, and EFS, the amount of time after treatment where the cancer has not come back or gotten worse.
The median EFS was 31.6 month for patients who received nivolumab plus chemotherapy compared with 20.8 months for chemotherapy alone. For the nivolumab/chemotherapy arm, 24% of patients reached pCR, versus 2.2% in the chemotherapy-alone arm. Overall survival (OS) is a secondary endpoint and an interim analysis showed that the two-year OS was 83% among patients who received the combination and 71% for those who received chemotherapy.
“Preliminary overall survival analysis showed a trend of improvement with nivolumab plus chemotherapy versus chemotherapy alone,” said Nicolas Girard, MD, PhD, lead author of the study and professor of respiratory medicine at Versailles Saint Quentin University and head of the Curie-Montsouris Thorax Institute in Paris.
Among patients treated with nivolumab and chemotherapy, 33.5% experienced grade 3 or 4 adverse events (AEs), as did 36.9% who received chemotherapy alone. The most common grade 3 or 4 AEs were neutropenia and decreased neutrophil count, which increases risk for serious infection.
Dr. Girard reported relationships with several companies, including Bristol Myers Squibb, Roche, and Novartis.
Dr. Carbone also reported relationships with many companies, including AstraZeneca, Bristol Myers Squibb, and Janssen.