A perioperative regimen combining neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab demonstrated statistically significant and clinically meaningful improvement in event-free survival compared to chemotherapy alone in patients with resectable non-small cell lung cancer, according to results from the phase 3 CheckMate 77T trial presented at the European Society for Medical Oncology Congress 2023.
The study, led by Tina Cascone, MD, PhD, Associate Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, represents the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy approach.
Primary Efficacy Results
After a median follow-up of 25.4 months, median event-free survival was not reached in the nivolumab/chemotherapy arm compared to 18.4 months in the placebo/chemotherapy arm, yielding a hazard ratio of 0.58 (P=0.00025). This represents a 42% reduction in the risk of recurrence, disease progression, or death.
The 12-month event-free survival rates were 73% in the nivolumab arm versus 59% in the placebo arm, while 18-month rates were 70% versus 50%, respectively. "The 18-month EFS rates suggest greater benefit for patients over time," Dr. Cascone noted during her presentation.
Pathologic Response Outcomes
The study revealed dramatic improvements in pathologic response rates with nivolumab treatment. Pathologic complete response was observed in 25.3% of patients in the nivolumab arm versus 4.7% in the chemotherapy arm, representing more than a fourfold increase. Major pathologic response occurred in 35.4% of nivolumab-treated patients compared to 12.1% of those receiving chemotherapy alone, nearly a threefold increase.
Subgroup Analysis
The benefit of nivolumab on event-free survival was observed across most patient subgroups. Patients with stage III disease showed particular benefit, and those with nodal disease, including both single and multistation N2 status, demonstrated improved event-free survival with nivolumab. The treatment favored nivolumab regardless of tumor histology, with particularly clear benefit in patients with squamous disease.
In patients with tumor PD-L1 expression less than 1%, median event-free survival was 29 months with nivolumab versus 19.8 months with placebo (HR 0.73). The magnitude of benefit was numerically greater in patients with PD-L1 expression of 1% or greater, where median event-free survival was not reached with nivolumab compared to 15.8 months with placebo (HR 0.52).
Study Design and Patient Population
The global, randomized, double-blind, placebo-controlled CheckMate 77T study enrolled 461 patients with resectable stage IIA to IIIB NSCLC. Patients were randomized 1:1 to receive either neoadjuvant nivolumab (360 mg every 3 weeks) plus chemotherapy for 4 cycles followed by surgery and adjuvant nivolumab (480 mg every 4 weeks for 1 year), or neoadjuvant chemotherapy plus placebo followed by surgery and adjuvant placebo.
Baseline characteristics were well-balanced between treatment arms. The median patient age was approximately 66 years, with more than 50% of patients from Europe and more than 20% from Asia. Approximately two-thirds had stage III disease at presentation, and approximately 90% were current or former smokers. More than 50% of patients in each arm had tumor PD-L1 expression of 1% or greater.
Treatment Delivery and Surgery
Some 78% of patients in the nivolumab arm and 77% in the chemotherapy arm underwent definitive surgery. Lobectomy was the most common surgical procedure, performed in 80% of patients in the nivolumab arm and 72% in the placebo arm. Nearly two-thirds of patients across both arms received adjuvant treatment, with a median of 13 doses administered.
Safety Profile
The perioperative nivolumab-based regimen showed no new safety signals. A similar percentage of patients in both arms experienced grade 3/4 treatment-related adverse events. Any-grade treatment-related adverse events were observed in 50% of patients treated with adjuvant nivolumab/chemotherapy and 30% of those treated with adjuvant placebo/chemotherapy.
Any-grade surgery-related adverse events were reported in 41% of nivolumab-treated patients and 39% of placebo-treated patients. Treatment-related deaths occurred in 2 patients (1%) in the nivolumab arm: one due to grade 5 pneumonitis and one due to grade 4 pneumonitis, both occurring after completion of neoadjuvant treatment.
Clinical Implications
"CheckMate 77T is the first phase 3 perioperative study to build on the standard of care, neoadjuvant nivolumab plus chemotherapy, and supports perioperative nivolumab as a potential new treatment option for patients with resectable NSCLC," Dr. Cascone stated.
The study demonstrated that neoadjuvant nivolumab plus chemotherapy continued to provide benefit over chemotherapy alone even in patients who were not able to receive adjuvant therapy, suggesting the neoadjuvant component contributes meaningfully to the overall treatment effect.
As of the September 6, 2023 database lock, overall survival data has not yet been formally tested and continues to mature, representing an important future milestone for the study.
