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Cited by 2,825Lung Cancer Diagnosis and TreatmentLung Cancer Treatments and MutationsLung Cancer Research Studies

Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer

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Forde, Patrick M., Spicer, Jonathan, Lu, Shun, Provencio, Mariano, Mitsudomi, Tetsuya, Awad, Mark M., Felip, Enriqueta, Broderick, Stephen R. +21 more·2022·New England Journal of Medicine
DOI 10.1056/nejmoa2202170PMC PMC9844511
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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.).

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  • In perioperative HCC, no surrogate endpoint has been validated, unlike pathological complete response in NSCLC and breast cancer.

    “Given the lack of successful trials in the perioperative space in HCC, no surrogate end point has been validated yet, as is the case for pCR in patients with NSCLC20,120 and breast cancer8.”

    From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [20]

    The Discussion says that a trial-level association between pathological complete response and survival in NSCLC had not been shown prospectively. It describes pathological complete response as promising and says its association with survival benefit requires further evaluation, contrary to the claim that it is a validated surrogate endpoint in NSCLC. This paper does not assess surrogate-endpoint validation in HCC. (LLM, conf=0.88)

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  • Neoadjuvant immune checkpoint inhibitor efficacy and safety are firmly established in multiple tumour types, with FDA approvals for NSCLC and triple-negative breast cancer.

    “Since results from one of the first clinical trials of such a therapeutic approach in patients with NSCLC were reported in 2018 (ref. 19), the efficacy and safety of neoadjuvant ICIs have been firmly established in multiple tumour types, with FDA approvals for two indications (NSCLC20,120 and triple-negative breast cancer8).”

    From Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma (2024) · cites this paper as [20]

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Authors
Forde, P. M., Spicer, J., Lu, S., Provencio, M., Mitsudomi, T., Awad, M. M., Felip, E., Broderick, S. R., Brahmer, J. R., Swanson, S. J., Kerr, K., Wang, C., Ciuleanu, T.-E., Saylors, G. B., Tanaka, F., Ito, H., Chen, K.-N., Liberman, M., Vokes, E. E., Taube, J. M., Dorange, C., Cai, J., Fiore, J., Jarkowski, A., Balli, D., Sausen, M., Pandya, D., Calvet, C. Y., & Girard, N.
Affiliations
  • Johns Hopkins University (US)
  • From the Bloomberg–Kimmel Institute for Cancer Immunotherapy, Johns Hopkins Kimmel Cancer Center, Baltimore (P.M.F., S.R.B., J.R.B., J.M.T.); McGill University Health Center (J.S.), and Centre Hospitalier de l’Université de Montréal (M.L.) — both in Montreal; Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai (S.L.), Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin (C.W.), and Peking University School of Oncology, Beijing Cancer Hospital, Beijing (K.-N.C.) — all in China; Hospital Universitario Puerta de Hierro, Madrid (M.P.); Kindai University Faculty of Medicine, Ohno-Higashi, Osaka-Sayama (T.M.), the University of Occupational and Environmental Health, Kitakyushu (F.T.), and Kanagawa Cancer Center, Yokohama (H.I.) — all in Japan; Dana–Farber Cancer Institute, Boston (M.M.A., S.J.S.); Vall d’Hebron Institute of Oncology, Barcelona (E.F.); Aberdeen Royal Infirmary, Aberdeen, United Kingdom (K.K.); Institutul Oncologic Prof. Dr....
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2022-05-26
Volume
386
Issue
21
Pages
1973-1985
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2202170
PMC
PMC9844511
OpenAlex
W4223502512
Cited by
2,825
References
38
Citations by year
2026: 583 · 2025: 683 · 2024: 724 · 2023: 624 · 2022: 209
FWCI
361.74
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
Bristol-Myers Squibb (N/A)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
Keywords
nivolumab, neoadjuvant therapy, non-small cell lung cancer, resectable lung cancer, platinum-based chemotherapy, immune checkpoint inhibitors, event-free survival, pathological complete response, overall survival, treatment-related adverse events
MeSH terms
Antineoplastic Agents, Immunological, Ipilimumab, Nivolumab, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Neoplasm Recurrence, Local, Platinum Compounds, Neoadjuvant Therapy

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