Trial reportNature medicine2021
Neoadjuvant nivolumab or nivolumab plus ipilimumab in operable non-small cell lung cancer: the phase 2 randomized NEOSTAR trial.
3 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph
Trial report in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 405 papers, 10 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
405citing papers in PubMed, 10 pooled it
44.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Study of Induction Checkpoint Blockade for Untreated Stage I-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection
NCT06218069 phase2 / phase3not yet recruitingnot on this mapstarted 2025, after this paper: background citation
Immuno-pet IMaging ResPonses AdministeRed Immune CheckpoiNt InhibiTor (IMPRINT)
TRIPL: Thoracic Radiotherapy and Inhibition of PD-1 and LAG-3 for Locally Advanced Non-Small Cell Lung Cancer
Who cites it
405 citing papers in PubMed, 10 syntheses or guidelines pooled it, 588 citations in OpenAlex.
- Cancer-related fatigue during treatment with neoadjuvant and/or adjuvant immune checkpoint inhibitors: a systematic review and meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Pooled it
- Global research trends and thematic evolution in neoadjuvant therapy and surgery for non-small cell lung cancer: a bibliometric and scientometric analysis.Frontiers in immunology · 2026Pooled it
- Pooled it
- Neoadjuvant immunotherapy for NSCLC: superior combination strategies, optimal treatment cycles, and predictive indicators from a Bayesian meta-analysis.Frontiers in immunology · 2025Pooled it
- Comparative Efficacy and Safety of Neoadjuvant Immunotherapy with Nivolumab vs. Pembrolizumab in Resectable Non-Small Cell Lung Cancer: A Systematic Review.Current oncology (Toronto, Ont.) · 2024Pooled it
- A Meta-Analysis of Efficacy and Safety of Neoadjuvant Immunotherapy Plus Chemotherapy for Resectable Non-Small Cell Lung Cancer.The clinical respiratory journal · 2024Pooled it
- Efficacy and safety of neoadjuvant immunotherapy protocols and cycles for non-small cell lung cancer: a systematic review and meta-analysis.Frontiers in oncology · 2024Pooled it
- A meta-analysis of the efficacy of programmed cell death 1/its ligand inhibitors plus cytotoxic T-lymphocyte-associated antigen 4 inhibitors in non-small cell lung cancer.Frontiers in pharmacology · 2024Pooled it
- Prognosis prediction using significant pathological response following neoadjuvant immunotherapy in resectable non-small-cell lung tumors: a meta-analysis.Frontiers in surgery · 2024Pooled it
- Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis.World journal of surgical oncology · 2023Pooled it
- Neoadjuvant Atezolizumab and Chemotherapy for Non-Squamous Non-Small Cell Lung Cancer: Efficacy and Safety Results of an Open-Label, Single-Arm, Phase II Trial.International journal of cancer · 2026Trial
- Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): conventional and distribution-based immune profiling of the tumor microenvironment and peripheral circulation.Journal for immunotherapy of cancer · 2025Trial
- Consolidative nivolumab versus observation in unresectable stage III non-small cell lung cancer patients following neoadjuvant nivolumab plus chemotherapy and concurrent chemoradiotherapy (CA209-7AL): a randomized clinical trial.Signal transduction and targeted therapy · 2025Trial
- Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: results of the NEOMUN trial.Journal for immunotherapy of cancer · 2025Trial
- Neoadjuvant Nivolumab Plus Ipilimumab Versus Chemotherapy in Resectable Lung Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Perioperative pembrolizumab in early-stage non-small cell lung cancer (NSCLC): safety, efficacy, and exploratory biomarker analysis.Journal for immunotherapy of cancer · 2025Trial
- Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings.Journal for immunotherapy of cancer · 2024Trial
- High peripheral T cell diversity is associated with lower risk of toxicity and superior response to dual immune checkpoint inhibitor therapy in patients with metastatic NSCLC.Journal for immunotherapy of cancer · 2024Trial
- Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial.Cancer cell · 2024Trial
- Neoadjuvant nivolumab or nivolumab plus ipilimumab in early-stage triple-negative breast cancer: a phase 2 adaptive trial.Nature medicine · 2024Trial
345 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
53 authors at 1 institution in 3 countries.
Tina CasconeThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA. tcascone@mdanderson.org.ORCID http://orcid.org/0000-0003-3008-5407
William N WilliamThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Annikka WeissferdtPathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cheuk H LeungBiostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Heather Y LinBiostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Apar PataerThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Myrna C B GodoyThoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Brett W CarterThoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lorenzo FedericoMelanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Alexandre ReubenThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4510-0382
Md Abdul Wadud KhanSurgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-0596-862X
Hitoshi DejimaTranslational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-2401-4357
Alejandro Francisco-CruzTranslational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Edwin R ParraTranslational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9068-1636
Luisa M SolisTranslational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1253-630X
Junya FujimotoTranslational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hai T TranThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Neda KalhorPathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Frank V FossellaThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Frank E MottThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anne S TsaoThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
George BlumenscheinThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiuning LeThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jianjun ZhangThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7872-3477
Ferdinandos SkoulidisThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jonathan M KurieThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mehmet AltanThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Charles LuThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bonnie S GlissonThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lauren Averett ByersThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0780-2677
Yasir Y ElaminThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Reza J MehranThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
David C RiceThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Garrett L WalshThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Wayne L HofstetterThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jack A RothThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8955-1313
Mara B AntonoffThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Humam KadaraTranslational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cara HaymakerTranslational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-1317-9287
Chantale BernatchezMelanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nadim J AjamiGenomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Robert R JenqGenomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Padmanee SharmaGenitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-4658-055X
James P AllisonImmunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Andrew FutrealGenomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-8663-2671
Jennifer A WargoSurgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-3438-7576
Ignacio I WistubaThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Stephen G SwisherThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-3080-1920
J Jack LeeBiostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5469-9214
Don L GibbonsThoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0003-2362-3094
Ara A VaporciyanThoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
John V Heymach *Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9068-8942
Boris Sepesi *Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4MNCI NIH HHS P30 CA016672NCI NIH HHS P50 CA070907
Abstract
Ipilimumab improves clinical outcomes when combined with nivolumab in metastatic non-small cell lung cancer (NSCLC), but its efficacy and impact on the immune microenvironment in operable NSCLC remain unclear. We report the results of the phase 2 randomized NEOSTAR trial (NCT03158129) of neoadjuvant nivolumab or nivolumab + ipilimumab followed by surgery in 44 patients with operable NSCLC, using major pathologic response (MPR) as the primary endpoint. The MPR rate for each treatment arm was tested against historical controls of neoadjuvant chemotherapy. The nivolumab + ipilimumab arm met the prespecified primary endpoint threshold of 6 MPRs in 21 patients, achieving a 38% MPR rate (8/21). We observed a 22% MPR rate (5/23) in the nivolumab arm. In 37 patients resected on trial, nivolumab and nivolumab + ipilimumab produced MPR rates of 24% (5/21) and 50% (8/16), respectively. Compared with nivolumab, nivolumab + ipilimumab resulted in higher pathologic complete response rates (10% versus 38%), less viable tumor (median 50% versus 9%), and greater frequencies of effector, tissue-resident memory and effector memory T cells. Increased abundance of gut Ruminococcus and Akkermansia spp. was associated with MPR to dual therapy. Our data indicate that neoadjuvant nivolumab + ipilimumab-based therapy enhances pathologic responses, tumor immune infiltrates and immunologic memory, and merits further investigation in operable NSCLC.
Indexed as
AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleHumansIpilimumabLung NeoplasmsMaleMiddle AgedNeoadjuvant TherapyNivolumabBiomarkers, TumorIpilimumabNivolumab
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.