STUDY DESIGN
Nivolumab + chemotherapy is an established standard-of-care neoadjuvant treatment for eligible patients with resectable non-small cell lung cancer (NSCLC).1 It is the sole neoadjuvant-only chemoimmunotherapy regimen approved in the United States, the European Union, and some other countries.1 In the phase 3 CheckMate 816 study, nivolumab + chemotherapy demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathological complete response (pCR) compared with chemotherapy alone in patients with resectable NSCLC.1 In this preplanned final analysis of overall survival (OS) from the trial, the efficacy and safety of neoadjuvant nivolumab + chemotherapy were evaluated over a minimum follow-up of 5 years.1
The trial enrolled 358 participants with newly diagnosed, resectable stage IB (≥4cm)-IIIA NSCLC per tumor, node, metastasis (TNM) 7th edition, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤1, and no known EGFR mutations or ALK alterations.1 Patients were stratified by disease stage, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS), and sex.1
Participants were randomized 1:1 to receive neoadjuvant nivolumab 360mg + chemotherapy (n=179) or chemotherapy alone (n=179), administered every 3 weeks for 3 cycles prior to surgery.1 Surgical resection was planned to occur within 6 weeks after completion of neoadjuvant therapy.1 Postoperative adjuvant chemotherapy, radiotherapy, or both were permitted.1
The dual primary endpoints were pCR and EFS.1 The key secondary endpoint presented was overall survival (OS).1 Exploratory analyses included OS stratified by circulating tumor DNA (ctDNA) clearance and pCR status, along with lung cancer-specific survival.1
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FINDINGS
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Primary endpoints:
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- The dual primary endpoints were pCR and EFS1
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- Overall, 24% of patients in the nivolumab group achieved pCR vs. only 2.2% in the chemotherapy group1
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- Among patients who achieved pCR with nivolumab + chemotherapy, 88% remained event-free at 5 years, compared to 35% of those without pCR (HR=0.14; 95% CI: 0.06-0.33)1
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- At 5 years, the hazard ratio for EFS continues to favour nivolumab + chemotherapy over chemotherapy alone1
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- Neoadjuvant nivolumab + chemotherapy significantly improved EFS vs. chemotherapy alone (median EFS: 59.6 months vs. 21.1 months; HR=0.68; 95% CI: 0.51-0.91), with 5-year EFS rates of 49% vs. 34%, respectively1
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Key secondary endpoint:
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- The key secondary endpoint presented was OS1
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- At a median follow-up of 68 months, the final analysis demonstrated a statistically significant OS benefit in the neoadjuvant nivolumab + chemotherapy group vs. chemotherapy alone1
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- Median OS was not reached in the nivolumab + chemotherapy group vs. 73.7 months in the chemotherapy group (HR=0.72; 95% CI: 0.523-0.998; p=0.0479), with 5-year OS rates of 65% vs. 55%, respectively1• Median OS was not reached in the nivolumab + chemotherapy group vs. 73.7 months in the chemotherapy group (HR=0.72; 95% CI: 0.523-0.998; p=0.0479), with 5-year OS rates of 65% vs. 55%, respectively1
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- OS benefits were consistent across subgroups by tumor PD-L1 expression and baseline stage of disease and histology1
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- Patients achieving pCR with nivolumab + chemotherapy had marked OS improvement compared to those without pCR (HR=0.11; 95% CI: 0.04-0.36), with 5-year OS rates of 95% vs. 56%1
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Exploratory analysis:
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- Presurgical ctDNA clearance was associated with long-term OS improvement in both treatment groups1
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- At 5 years, OS was 75% among patients with ctDNA clearance vs. 53% in those without (HR for death=0.38 in the nivolumab + chemotherapy group vs.0.39 in the chemotherapy-only group)1
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- The nivolumab + chemotherapy group showed an improvement in lung cancer–specific survival at 5 years, with a rate of 75% compared to 65% with chemotherapy alone (HR=0.65; 95% CI: 0.44-0.96)1
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Safety:
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- The long-term safety profile of neoadjuvant nivolumab + chemotherapy was consistent with previous reports1
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- Any-grade treatment-related adverse events (TRAEs) occurred in 84% of patients in the nivolumab + chemotherapy group and 90% in the chemotherapy group1
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- Grade 3-4 TRAEs were reported in 36% of patients receiving nivolumab + chemotherapy vs. 38% with chemotherapy alone1
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- Any-grade TRAEs leading to discontinuation occurred in 10% of participants in both groups1
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- Any-grade treatment-related serious adverse events (SAEs) were reported in 12% of patients in the nivolumab + chemotherapy group vs. 10% in the chemotherapy group1
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