# CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery

Source: https://onco.cc/key-papers/paper-checkmate-816-nejm-2022/  
OnCo record `paper-checkmate-816-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Just three cycles of chemotherapy with the immunotherapy nivolumab before surgery wiped out all viable tumour in a quarter of patients and reduced relapse or death by about a third, without making surgery harder.

## Summary

Open-label phase 3 trial of 358 patients with resectable stage IB-IIIA NSCLC randomised to three cycles of neoadjuvant nivolumab plus platinum-doublet chemotherapy or chemotherapy alone, followed by surgery. Primary endpoints were pathological complete response (pCR) and event-free survival (EFS).

pCR was 24.0% vs 2.2% and median EFS 31.6 vs 20.8 months (HR 0.63). Surgery rates and complications were not worse with nivolumab. A 2025 report confirmed an overall survival benefit (HR about 0.72). It was the first neoadjuvant immunotherapy approval in lung cancer and, together with the perioperative trials (KEYNOTE-671, AEGEAN, CheckMate 77T), moved immunotherapy before surgery.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2202170
- Authors: Forde PM, Spicer J, Lu S, et al.
- Findings: Pathological complete response 24.0% vs 2.2% (odds ratio 13.9).; Median event-free survival 31.6 vs 20.8 months; HR 0.63 (97.38% CI 0.43-0.91).; Definitive surgery was performed in 83% vs 75% of patients; grade 3-4 surgery-related adverse events 11% in both arms.; Patients achieving pCR had markedly better EFS (HR about 0.13 within the nivolumab arm).; Overall survival (2025 update): HR about 0.72, with 5-year OS of roughly 65% vs 55%.
- What it means: Patients with operable stage II-III lung cancer without EGFR or ALK alterations should have chemo-immunotherapy discussed before surgery rather than only afterwards. Three pre-operative cycles do not compromise the operation and improve cure rates. Whether to continue immunotherapy after surgery, as the perioperative trials do, and whether patients with pCR need any further treatment, remain open questions.
- Caveats: Open-label; EFS by blinded review.; About one in six patients did not proceed to surgery in either arm, an under-appreciated risk of any neoadjuvant strategy.; Benefit was smaller in stage IB-II and in PD-L1-negative tumours.; No adjuvant immunotherapy was given, so the trial cannot say whether the perioperative approach adds value over neoadjuvant alone.

## Sources

- NEJM 2022: https://doi.org/10.1056/NEJMoa2202170
- ClinicalTrials.gov NCT02998528: https://clinicaltrials.gov/study/NCT02998528

## Connected records

- roadmaps: [Lung cancer roadmap: from Doll and Hill and the naming of tobacco, through the cytotoxic plateau, computed tomography screening, EGFR and ALK, immunotherapy by PD-L1, the perioperative trials and PACIFIC, to DLL3 in small-cell disease and a 2032 registry watch](https://onco.cc/roadmaps/lung-cancer-evidence-roadmap/)
- key papers: [Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)](https://onco.cc/key-papers/paper-felip-impower010-adjuvant-atezolizumab-lancet-2021/), [Perioperative durvalumab for resectable non-small-cell lung cancer](https://onco.cc/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/), [Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer](https://onco.cc/key-papers/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023/)
- cancers: [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Resectable stage I to III non-small-cell lung cancer](https://onco.cc/cancers/resectable-nsclc/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/)
- institutions: [Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center](https://onco.cc/institutions/johns-hopkins/)
- terms: [Event-free / disease-free survival (EFS, DFS, iDFS, RFS)](https://onco.cc/terms/efs/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- people: [Enriqueta Felip](https://onco.cc/people/enriqueta-felip/), [Everett E. Vokes](https://onco.cc/people/everett-vokes/), [Jonathan Spicer](https://onco.cc/people/jonathan-spicer/), [Julie R. Brahmer](https://onco.cc/people/julie-brahmer/), [Patrick M. Forde](https://onco.cc/people/patrick-forde/), [Shun Lu](https://onco.cc/people/lu-shun/), [Tina Cascone](https://onco.cc/people/tina-cascone/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- trials: [CheckMate 816](https://onco.cc/trials/checkmate-816/)

---
JSON: https://onco.cc/api/v1/entities/paper-checkmate-816-nejm-2022.json