# Perioperative nivolumab and chemotherapy in stage III non-small-cell lung cancer

Source: https://onco.cc/key-papers/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023/  
OnCo record `paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A Spanish trial of 86 patients with stage III lung cancer. Adding immunotherapy before surgery left 37 percent with no viable tumour in the specimen against 7 percent, and 85 percent were alive at two years against 64.

## Summary

The NADIM II investigators, reported by Provencio, Nadal, Gonzalez-Larriba and colleagues, randomised 86 patients with resectable stage IIIA or IIIB non-small-cell lung cancer to neoadjuvant nivolumab with platinum chemotherapy or chemotherapy alone, followed by surgery, with six months of adjuvant nivolumab after an R0 resection in the experimental group. The primary endpoint was pathological complete response.

It is a small investigator-initiated phase 2 trial with an effect size the large industry trials have not matched, and it is the trial that made pathological complete response credible as a surrogate. It also showed something the larger trials mostly do not report: more patients in the immunotherapy arm actually reached the operating theatre.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Tags: lung-evidence
- Journal: New England Journal of Medicine
- Year: 2023
- DOI: 10.1056/NEJMoa2215530
- Authors: Provencio M, Nadal E, Gonzalez-Larriba JL, et al.
- Findings: Pathological complete response in 37 percent of the nivolumab group against 7 percent of the control group (relative risk 5.34, 95 percent confidence interval 1.34 to 21.23; P equals 0.02).; Surgery was performed in 93 percent of the nivolumab group against 69 percent of controls (relative risk 1.35, 1.05 to 1.74).; Progression-free survival at 24 months 67.2 percent against 40.9 percent (hazard ratio 0.47, 0.25 to 0.88).; Overall survival at 24 months 85.0 percent against 63.6 percent (hazard ratio for death 0.43, 0.19 to 0.98).; Grade 3 or 4 adverse events in 11 of 57 patients (19 percent) in the experimental group and 3 of 29 (10 percent) in the control group.; 86 patients underwent randomisation, 57 to the experimental group and 29 to the control group.
- What it means: The strongest signal that neoadjuvant immunotherapy makes stage III lung cancer operable as well as more often curable. Twenty-four percentage points more patients reaching surgery is a result that only a neoadjuvant design can produce.
- Caveats: 86 patients in a phase 2 trial; the confidence intervals are wide and the overall survival hazard ratio only just excludes one.; Open-label, with chemotherapy alone as the comparator, in a single country.; The adjuvant nivolumab component means the trial cannot separate the effect of treatment before surgery from treatment after it.

## Sources

- N Engl J Med 2023: https://doi.org/10.1056/NEJMoa2215530
- PubMed: https://pubmed.ncbi.nlm.nih.gov/37379158/
- ClinicalTrials.gov NCT03838159: https://clinicaltrials.gov/study/NCT03838159

## Connected records

- key papers: [CheckMate 816: three cycles of nivolumab plus chemotherapy before lung cancer surgery](https://onco.cc/key-papers/paper-checkmate-816-nejm-2022/), [Perioperative durvalumab for resectable non-small-cell lung cancer](https://onco.cc/key-papers/paper-heymach-aegean-perioperative-durvalumab-nejm-2023/), [Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer](https://onco.cc/key-papers/paper-keynote-671-n-engl-j-med-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/)
- fronts: [Immunotherapy](https://onco.cc/fronts/immunotherapy/), [Surgery & Interventional](https://onco.cc/fronts/surgery/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Cisplatin](https://onco.cc/drugs/cisplatin/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- companies: [Bristol Myers Squibb](https://onco.cc/companies/bms/)
- terms: [Immune checkpoint](https://onco.cc/terms/immune-checkpoint/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/)
- bottlenecks: [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- 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/)

---
JSON: https://onco.cc/api/v1/entities/paper-provencio-nadim-ii-perioperative-nivolumab-stage-iii-nejm-2023.json