An exploratory analysis of the phase 3 CheckMate 77T trial has revealed that perioperative nivolumab (Opdivo) plus platinum-based chemotherapy provides consistent clinical benefits in patients with resectable non-small cell lung cancer (NSCLC), regardless of the number of neoadjuvant treatment cycles completed. The findings, presented at the 2024 European Lung Cancer Congress, support the broader applicability of this immunotherapy regimen in the perioperative setting.
Pathological Response Rates Show Consistent Benefit
Among patients who completed the full 4-cycle neoadjuvant regimen, those receiving nivolumab (n = 191) achieved a pathological complete response (pCR) rate of 26.7% compared to 5.4% in the placebo arm (n = 205). For patients who proceeded to surgical resection, the pCR rates were even more pronounced at 32.3% for nivolumab (n = 158) versus 6.5% for placebo (n = 168).
Importantly, the benefit extended to patients who received fewer than 4 neoadjuvant cycles. In this subgroup, nivolumab-treated patients (n = 38) achieved an 18.4% pCR rate compared to 0% in the placebo group (n = 27). Among the 7 patients who experienced pCR in the nivolumab arm, 3 received 3 treatment cycles and 4 received 2 cycles. For patients who underwent resection, the pCR rates were 35.0% for nivolumab (n = 20) and 0% for placebo (n = 10).
"These results further support perioperative use of nivolumab as a potential new treatment option for our patients [with resectable NSCLC], building upon the standard of care of using chemoimmunotherapy in the neoadjuvant setting," said lead study author Mark A. Awad, MD, PhD, director of Clinical Research and associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute.
Major Pathological Response and Survival Outcomes
The analysis also examined major pathological response (MPR) rates, which showed similar patterns. In patients completing 4 neoadjuvant cycles, MPR rates were 38.2% for nivolumab versus 13.7% for placebo. Among those who underwent resection, the rates were 46.2% and 16.7%, respectively.
For patients receiving fewer than 4 cycles, MPR rates were 21.1% for nivolumab and 0% for placebo. Among those who underwent resection in this subgroup, 40% of nivolumab-treated patients achieved MPR compared to 0% in the placebo group.
Event-free survival (EFS) data demonstrated the durability of treatment benefits. For patients completing 4 neoadjuvant cycles, median EFS was not reached in the nivolumab arm compared to 19.8 months for placebo (HR, 0.57; 95% CI, 0.42-0.79), with 12-month EFS rates of 76% and 61%, respectively.
Even in patients receiving fewer than 4 cycles, the nivolumab arm showed improved outcomes with median EFS not reached versus 7.8 months for placebo (HR, 0.51; 95% CI, 0.23-1.11), and 12-month EFS rates of 62% versus 36%.
Time to Distant Metastasis Analysis
The analysis revealed favorable trends in time to distant metastasis (TTDM) across all patient subgroups. For the overall study population, median TTDM was not reached for nivolumab versus 38.8 months for placebo (HR, 0.62; 95% CI, 0.44-0.85). In patients completing 4 neoadjuvant cycles, median TTDM was not reached for nivolumab compared to 38.8 months for placebo (HR, 0.61; 95% CI, 0.42-0.88).
Notably, patients who received fewer than 4 neoadjuvant cycles showed particularly strong TTDM benefits, with median TTDM not reached for nivolumab versus 10.9 months for placebo (HR, 0.46; 95% CI, 0.22-0.98).
Treatment Completion and Safety Profile
The study found that 83% of patients in the nivolumab arm and 88% in the placebo arm completed 4 cycles of neoadjuvant treatment. Among nivolumab patients who received fewer than 4 cycles, discontinuation reasons included study drug toxicity (55%), disease progression (8%), and other factors (26%). In the placebo arm, discontinuation was due to study drug toxicity (41%), disease progression (11%), and other reasons (41%).
For adjuvant treatment, 69% of nivolumab patients who completed 4 neoadjuvant cycles received adjuvant therapy compared to 71% in the placebo arm, with both groups receiving a median of 13 adjuvant cycles. Among those completing fewer than 4 neoadjuvant cycles, 29% and 26% of patients in the nivolumab and placebo arms, respectively, received adjuvant treatment.
Safety data showed that 87% of nivolumab patients who completed 4 neoadjuvant cycles experienced any-grade adverse events during adjuvant treatment versus 80% in the placebo arm. Treatment-related adverse event rates were 50% for nivolumab and 30% for placebo. Discontinuation rates due to adverse events were 14% for nivolumab and 4% for placebo.
Regulatory Progress and Study Design
The CheckMate 77T trial enrolled patients aged 18 years or older with suspected or histologically confirmed stage IIA to IIIB NSCLC considered resectable. Key inclusion criteria included available tumor tissue for biomarkers and ECOG performance status of 0 or 1. Patients with brain metastases, prior systemic NSCLC therapy, EGFR mutations, or ALK alterations were excluded.
In February 2024, the FDA accepted a supplemental biologics license application for neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab for perioperative treatment of resectable stage IIA to IIIB NSCLC. The European Medicines Agency validated a similar application. These regulatory submissions were based on the trial's primary endpoint data showing statistically significant improvement in EFS (HR, 0.58; 97.36% CI, 0.42-0.81; P = .00025).
"Most patients who could receive adjuvant nivolumab after neoadjuvant chemoimmunotherapy received the full 1 year of [adjuvant] treatment, and [adjuvant nivolumab] had a manageable safety profile," Awad concluded.
