Neoadjuvant Nivolumab With Chemotherapy Yields Significant Overall Survival Benefit in Resectable NSCLC

Among adults with stage 1B to 3A resectable non-small cell lung cancer (R-NSCLC), nivolumab (Opdivo; Bristol Myers Squibb) in combination with chemotherapy—followed by surgery—demonstrated a statistically significant overall survival (OS) benefit compared with chemotherapy alone while continuing to improve event-free survival (EFS). These conclusions were presented as part of an abstract from the open-label, phase 3 CheckMate 816 trial (NCT02998528) at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, and subsequently published in the Journal of Clinical Oncology.^1,2

Nivolumab and chemotherapy is a standard of care option for resectable non-small cell lung cancer. | Image Credit: © RFBSIP - stock.adobe.com

Benefits of Nivolumab in Resectable NSCLC

Nivolumab is a fully human anti-programmed death 1 (PD-1) antibody designed to restore the function of antitumor T-cells. In combination with chemotherapy, which enhances antitumor immunity through activation of the immune system, it has been demonstrated to be an effective regimen for patients with NSCLC. For patients in the neoadjuvant setting, immunotherapy with agents such as nivolumab allows for earlier targeting of harmful cancer cells and possible improvements in OS rates.^3,4

Investigators determined that OS is an ideal end point for use in evaluating the efficacy of neoadjuvant therapy in resectable NSCLC. Thus far, improvements in EFS as well as complete response have been solidified by prior investigators. In CheckMate 816, median EFS was 31.6 months with the combination of nivolumab and chemotherapy, and 24.0% of patients reached a pathological complete response. Critically, adding nivolumab to neoadjuvant chemotherapy did not heighten the incidence of adverse events, affirming the role of the regimen as a standard of care treatment.³

At 5 Years, Nivolumab Sustains Overall Survival

After a 5-year follow-up period (median: 68 months), CheckMate 816 investigators have now reported the planned final analysis of OS from the trial. Neoadjuvant nivolumab with chemotherapy elicited a statistically meaningful OS benefit compared with chemotherapy alone (median OS not reached [NR] vs 73.7 months [95% CI, 47.3—NR]; hazard ratio [HR]: 0.72 [95% CI, 0.523—0.998]; P = .0479), according to the investigators. Accordingly, 5-year OS rates were 65% with nivolumab and chemotherapy versus 55% with chemotherapy alone.¹

A subgroup analysis was conducted, examining patients defined by tumor PD-L1 expression, histology, and baseline disease state. Among all these subgroups, OS favored nivolumab with chemotherapy. Furthermore, in an exploratory analysis of patients with circulating tumor DNA (ctDNA) at baseline (nivolumab and chemotherapy, n = 43; chemotherapy alone, n = 43), patients with presurgical ctDNA clearance (56% versus 35%) had continued OS improvement versus those without across both treatment arms (HR: nivolumab + chemo, 0.38 [95% CI, 0.15—1.00]; chemotherapy, 0.39 [95% CI, 0.14—1.11]), the investigators found.¹

Significant Improvements for Patients With Pathological Complete Response

In CheckMate 816, positive pCR rates were observed with nivolumab and chemotherapy treatment. For these patients, investigators observed sustained OS improvement compared to patients who were not treated with nivolumab (HR: 0.11 [95% CI, 0.04—0.36]; 5-year OS rates, 95% versus 56%). As demonstrated in the original analysis of CheckMate 816, neoadjuvant nivolumab and chemotherapy improved EFS compared with chemotherapy alone (median, 59.6 months [95% CI, 31.6—NR] vs 21.1 months [95% CI, 16.6—36.8]; HR: .068 [95% CI, 0.51—0.91]). Importantly, 5-year EFS rates were reported at 49% versus 34%.¹

Overall, the study authors determined that patients with pCR treated with neoadjuvant nivolumab and chemotherapy had around a 90% reduction in their risk of death at 5 years compared with those without pCR. The findings signify a long-term survival benefit from a relatively short cycle of treatment—patients received the nivolumab regimen once every 3 weeks—and solidify “a paradigm shift in the treatment of resectable NSCLC without actionable genomic alterations,” the abstract authors wrote in their conclusion.¹

REFERENCES

1. Forde PM, Spicer J, Provencio M, et al. Overall survival with neoadjuvant nivolumab (NIVO) + chemotherapy (chemo) in patients with resectable NSCLC in CheckMate 816. J Clin Oncol. 2025;43(17). doi:10.1200/JCO.2025.43.17_suppl.LBA800. Presented at: 2025 American Soceity of Clinical Oncology Annual Meeting; May 30 to June 3, 2025; Chicago, Illinois.

2. A Neoadjuvant Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Versus Chemotherapy Alone in Early Stage Non-Small Cell Lung Cancer (NSCLC) (CheckMate 816). National Library of Medicine. ClinicalTrials.gov Identifier: NCT02998528. Last Updated January 24, 2025. Accessed June 9, 2025.

3. Forde PM, Spicer K, Provencio M. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. 2022;386(21):1973-1985. doi:10.1056/NEJMoa2202170

4. Uprety D, Mandrekar SJ, Wigle D, et al. Neoadjuvant immunotherapy for NSCLC: Current concepts and future approaches. J Thoracic Oncol. 2020;15(8):1281-1297. doi:10.1016/j.jtho.2020.05.020