Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 May 26;386(21):1973-1985.
doi: 10.1056/NEJMoa2202170. Epub 2022 Apr 11.

Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer

Patrick M Forde  1 , Jonathan Spicer  1 , Shun Lu  1 , Mariano Provencio  1 , Tetsuya Mitsudomi  1 , Mark M Awad  1 , Enriqueta Felip  1 , Stephen R Broderick  1 , Julie R Brahmer  1 , Scott J Swanson  1 , Keith Kerr  1 , Changli Wang  1 , Tudor-Eliade Ciuleanu  1 , Gene B Saylors  1 , Fumihiro Tanaka  1 , Hiroyuki Ito  1 , Ke-Neng Chen  1 , Moishe Liberman  1 , Everett E Vokes  1 , Janis M Taube  1 , Cecile Dorange  1 , Junliang Cai  1 , Joseph Fiore  1 , Anthony Jarkowski  1 , David Balli  1 , Mark Sausen  1 , Dimple Pandya  1 , Christophe Y Calvet  1 , Nicolas Girard  1 ; CheckMate 816 Investigators
Collaborators, Affiliations
Clinical Trial

Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer

Patrick M Forde et al. N Engl J Med. .

Abstract

Background: Neoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.

Methods: In this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.

Results: The median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.

Conclusions: In patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

PubMed Disclaimer

Figures

Figure 1 (facing page).
Figure 1 (facing page).. Event-free Survival According to Blinded Independent Central Review.
Panel A shows event-free survival among the patients who underwent concurrent randomization, and Panel B shows event-free survival in prespecified patient subgroups. Event-free survival was defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence of disease after surgery (on the basis of assessment by blinded independent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1), progression of disease in the absence of surgery, or death from any cause; data on patients who received subsequent therapy were censored at the last tumor assessment that could be evaluated on or before the date of subsequent therapy. Eastern Cooperative Oncology Group (ECOG) performance-status scores range from 0 to 5, with higher scores reflecting greater disability. NR denotes not reached, PD-L1 programmed death ligand 1, and TMB tumor mutational burden.
Figure 2 (facing page).
Figure 2 (facing page).. Pathological Complete Response According to Blinded Independent Pathological Review.
Panel A shows pathological complete response in the primary analysis population, and Panel B shows pathological complete response in prespecified patient subgroups. Pathological complete response was defined as 0% residual viable tumor cells in both primary tumor (lung) and sampled lymph nodes. According to the intention-to-treat principle, patients who did not undergo surgery were counted as not having had a response for the primary analysis. In Panel A, the between-group difference was calculated by means of a stratified Cochran–Mantel–Haenszel method.
Figure 3.
Figure 3.. Overall Survival.
The 95% confidence interval of the hazard ratio was 0.38 to 0.87. At this first prespecified interim analysis, the P value for overall survival did not cross the boundary for statistical significance (0.0033).
See this image and copyright information in PMC

Comment in

Similar articles

  • Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer.
    Provencio M, Nadal E, González-Larriba JL, Martínez-Martí A, Bernabé R, Bosch-Barrera J, Casal-Rubio J, Calvo V, Insa A, Ponce S, Reguart N, de Castro J, Mosquera J, Cobo M, Aguilar A, López Vivanco G, Camps C, López-Castro R, Morán T, Barneto I, Rodríguez-Abreu D, Serna-Blasco R, Benítez R, Aguado de la Rosa C, Palmero R, Hernando-Trancho F, Martín-López J, Cruz-Bermúdez A, Massuti B, Romero A. Provencio M, et al. N Engl J Med. 2023 Aug 10;389(6):504-513. doi: 10.1056/NEJMoa2215530. Epub 2023 Jun 28. N Engl J Med. 2023. PMID: 37379158 Clinical Trial.
  • Perioperative Nivolumab in Resectable Lung Cancer.
    Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, Karaseva N, Kuzdzal J, Petruzelka LB, Wu L, Pujol JL, Ito H, Ciuleanu TE, de Oliveira Muniz Koch L, Janssens A, Alexandru A, Bohnet S, Moiseyenko FV, Gao Y, Watanabe Y, Coronado Erdmann C, Sathyanarayana P, Meadows-Shropshire S, Blum SI, Provencio Pulla M; CheckMate 77T Investigators. Cascone T, et al. N Engl J Med. 2024 May 16;390(19):1756-1769. doi: 10.1056/NEJMoa2311926. N Engl J Med. 2024. PMID: 38749033 Clinical Trial.
  • Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer.
    Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Hellmann MD, et al. N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231. Epub 2019 Sep 28. N Engl J Med. 2019. PMID: 31562796 Clinical Trial.
  • Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data.
    NSCLC Meta-analysis Collaborative Group. NSCLC Meta-analysis Collaborative Group. Lancet. 2014 May 3;383(9928):1561-71. doi: 10.1016/S0140-6736(13)62159-5. Epub 2014 Feb 25. Lancet. 2014. PMID: 24576776 Free PMC article. Review.
  • Comparative Efficacy and Safety of Neoadjuvant Immunotherapy with Nivolumab vs. Pembrolizumab in Resectable Non-Small Cell Lung Cancer: A Systematic Review.
    Papaporfyriou A, Bartziokas K, Apessos I, Mueller J, Leivaditis V, Koletsis E, Grapatsas K. Papaporfyriou A, et al. Curr Oncol. 2024 Oct 18;31(10):6289-6299. doi: 10.3390/curroncol31100469. Curr Oncol. 2024. PMID: 39451773 Free PMC article. Review.
See all similar articles

Cited by

See all "Cited by" articles

References

    1. Liang Y, Wakelee HA. Adjuvant chemotherapy of completely resected early stage non-small cell lung cancer (NSCLC). Transl Lung Cancer Res 2013;2:403–10. - PMC - PubMed
    1. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Transl Lung Cancer Res 2014;3:242–9. - PMC - PubMed
    1. Taylor MD, Nagji AS, Bhamidipati CM, et al. Tumor recurrence after complete resection for non-small cell lung cancer. Ann Thorac Surg 2012;93:1813–20. - PubMed
    1. National Comprehensive Cancer Network. Guidelines for treatment of cancer by type: non-small cell lung cancer. Version 2.2022. 2022.
    1. NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet 2014;383:1561–71. - PMC - PubMed

Publication types

MeSH terms

Associated data