Perioperative nivolumab (Opdivo) has shown a significant event-free survival (EFS) benefit compared to placebo in patients with resectable non-small cell lung cancer (NSCLC). The phase 3 CheckMate 77T study, presented at the 2024 European Society of Medical Oncology Congress, revealed a median EFS of 40.1 months in patients treated with perioperative nivolumab compared to 17.0 months in the placebo arm (HR, 0.59; 95% CI, 0.45-0.79). This improvement highlights the potential of nivolumab to enhance outcomes in this patient population.
Efficacy Outcomes
The CheckMate 77T study (NCT04025879) involved patients with resectable stage IIA to IIIB NSCLC who had not received prior systemic anticancer therapy. Patients were randomized to receive either nivolumab 360 mg or placebo every 3 weeks in combination with chemotherapy for up to 4 cycles, followed by surgery and adjuvant nivolumab 480 mg every 4 weeks or placebo for up to 13 cycles. The primary endpoint was EFS by blinded independent central review.
At a median follow-up of 33.3 months (range, 23.6-52.1), the 12-month EFS rates were 73% (95% CI, 67%-79%) in the nivolumab arm and 59% (95% CI, 52%-65%) in the placebo arm. The 24-month EFS rates were 65% (95% CI, 58%-71%) and 44% (95% CI, 38%-51%), respectively. Patients who achieved a pathologic complete response (pCR) with nivolumab (n = 58) also experienced a significant EFS benefit compared to those who received placebo (n = 11; HR, 0.59; 95% CI, 0.12-2.91).
Jonathan D. Spicer, MD, PhD, FRCS, from McGill University Health Centre, emphasized the clinical significance of these findings, stating, "The EFS data show an improvement that is both statistically and clinically significant with the addition of perioperative nivolumab, with an increase in median EFS from 17.0 months to 40.1 months."
ctDNA Analysis
Exploratory analyses of circulating tumor DNA (ctDNA) clearance during the neoadjuvant period showed that evaluable patients in the nivolumab arm (n = 76) achieved ctDNA clearance at a rate of 66% compared to 38% in the placebo arm (n = 64). The EFS HR among these patients was 0.38 (95% CI, 0.16-0.88) in favor of nivolumab, with 2-year EFS rates of 81% vs 58%, respectively. Furthermore, among evaluable patients with ctDNA clearance, the pCR rates were 50% in the nivolumab arm (n = 50) and 12% in the placebo arm (n = 24).
During the post-operative period, ctDNA recurrence rates were lower in the nivolumab arm (8%) compared to the placebo arm (20%) among evaluable patients. Specifically, patients with a pCR in the nivolumab arm (n = 26) experienced ctDNA recurrence at a rate of 4%, while those in the placebo arm (n = 5) had a recurrence rate of 20%.
Safety Profile
Regarding safety, all patients who achieved a pCR in both the nivolumab (n = 58) and placebo (n = 11) arms experienced any-grade adverse effects (AEs). Grade 3 to 4 AEs were reported in 48% of patients in the nivolumab arm and 46% in the placebo arm. Treatment-related AEs (TRAEs) of any grade occurred in 97% and 82% of patients, respectively. Serious AEs of any grade were observed in 43% and 36% of patients, respectively.
In patients without a pCR, any-grade AEs were reported in 96% of the nivolumab arm (n = 170) and 98% of the placebo arm (n = 219). Grade 3 to 4 AEs occurred in 46% and 42% of patients, respectively. Two treatment-related deaths were reported in the nivolumab arm, both due to pneumonitis.
Study Design and Patient Characteristics
The CheckMate 77T study enrolled patients with resectable stage IIA to IIIB NSCLC who had an ECOG performance status of 1 or less and did not have EGFR mutations or known ALK translocations. Patients were stratified by histology (nonsquamous vs squamous), disease stage (II vs III), and tumor PD-L1 expression (≥1% vs <1% vs not evaluable/indeterminate).
Baseline characteristics were well balanced between the nivolumab and placebo arms. The median patient age was 66 years in both arms. Most patients were from Europe (54% vs 55%), had an ECOG performance status of 0 (64% vs 61%), had stage IIIA-B disease (64% vs 64%), had squamous histology (51% vs 51%), and were current or former smokers (93% vs 88%).
