Nivolumab-Based Treatment Yields Long-Term Survival in Resectable NSCLC

Perioperative nivolumab (Opdivo)-based treatment demonstrated long-term survival among patients with resectable stage IIA to IIIA non–small cell lung cancer (NSCLC), especially among those with a pathological complete response (pCR), according to findings from a phase 2 trial (NCT04015778) presented in a poster session at the 2026 European Lung Cancer Congress.¹

After a median follow-up of 50.5 months, the event-free survival (EFS) and overall survival (OS) rates across the intent-to-treat population were 57.2% and 72.1%, respectively. At 4 years, the EFS rates were 79.7% among patients with a pCR, 62.5% among those with a major pathological response (MPR), and 43.8% in those without an MPR. The 4-year OS rates were 94.1%, 68.4%, and 69.4% in each respective patient subgroup.

The 3-year landmark (T3) EFS rates were 73.7% among patients with minimal residual disease (MRD) negativity vs 22.2% among those with MRD positivity. LAMPAD, an XGBoost-Cox model that integrates clinicopathological features with pre-operative (T2) and T3 biomarkers, appeared to effectively stratify the T3-negative cohort into low-risk and high-risk populations. The 3-year EFS rates across the low-risk and high-risk patient groups were 86.8% and 37.1%, respectively.

When excluding events during adjuvant therapy (n = 11), Spearman correlation analysis highlighted that the number of adjuvant cycles positively correlated with EFS outcomes (P = .0013), although non-linear analysis showed that survival benefit plateaued following 13 cycles. Additionally, those who received at least 13 cycles of therapy experienced an improved 3-year EFS rate of 79% vs 60% among those with fewer than 13 cycles (HR, 0.382; 95% CI, 0.165-0.885; P = .02). Among patients in the low-risk subgroup per LAMPAD criteria, the 3-year EFS rates were 88.2% in patients with at least 13 cycles of treatment vs 100% among those with fewer than 13 cycles.

“The LAMPAD model provides superior risk stratification,” lead study author Chen Huang, MD, PhD, from the Southern Medical University of Guandong Lung Cancer Institute at Guangdong Provincial People’s Hospital (Guandong Academy of Medical Sciences), wrote with coauthors in the poster.¹ "While 13 cycles of adjuvant [nivolumab] is recommended to maximize outcomes in the general population, LAMPAD low-risk patients may be candidates for treatment de-escalation.”

Investigators of this multicenter, 2-stage phase 2 trial enrolled patients with resectable, stage IIA to IIIA EGFR or ALK wild-type NSCLC. Cohort 2, which included 49 patients, was intended to confirm the results observed in cohort 1. Patients were assigned to receive nivolumab at 240 mg every 2 weeks or 360 mg every 3 weeks with or without carboplatin area under the curve 5 every 3 weeks and nab-paclitaxel (Abraxane) at 135 mg/m² on days 1 and 8 of each cycle.²

The study’s primary end point was EFS. Investigators evaluated T3 status per circulating tumor DNA within 30 days following surgery. Additionally, the LAMPAD model was leveraged to optimize risk stratification, while investigators used Spearman correlation to determine how adjuvant nivolumab cycles correlated with EFS outcomes.

Patients 18 years and older with stage IB to IIIA operable NSCLC confirmed in tissue, lung function capacity capable of tolerating proposed lung surgery, an ECOG performance status of 0 or 1, and availability of tissue from the primary lung tumor were eligible for enrollment on the trial. Those with locally advanced, inoperable, or metastatic disease; active, known, or suspected autoimmune disease; or prior treatment with any therapy that targets T cell co-stimulation pathways were ineligible for study entry.

References

1. Huang C, Liu SM, Zhang J, et al. Perioperative nivolumab monotherapy or combined with chemotherapy in resectable stage II-IIIA NSCLC (CTONG 1804): an interim analysis and MRD guide adaptive therapy exploration from a phase II trial. Presented at the 2026 European Lung Cancer Congress; March 25-28, 2026; Copenhagen, Denmark. Abstract 225P.
2. A two-arm (phase 2) exploratory study of nivolumab monotherapy or in combination with nab-paclitaxel and carboplatin in early stage NSCLC in China. ClinicalTrials.gov. Updated February 12, 2020. Accessed March 30, 2026. https://tinyurl.com/48xa7txz