Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial.

Autor: Cascone T; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. tcascone@mdanderson.org., Leung CH; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Weissferdt A; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pataer A; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Carter BW; Department of Thoracic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Godoy MCB; Department of Thoracic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Feldman H; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., William WN Jr; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Hospital BP, a Beneficencia Portuguesa de Sao Paulo, Sao Paulo, Brazil., Xi Y; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Basu S; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sun JJ; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Yadav SS; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Rojas Alvarez FR; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lee Y; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Mishra AK; Platform for Innovative Microbiome and Translational Research (PRIME-TR), Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chen L; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Pradhan M; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Guo H; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sinjab A; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhou N; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Negrao MV; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Le X; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gay CM; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Tsao AS; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Byers LA; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Altan M; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Glisson BS; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Fossella FV; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Elamin YY; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Blumenschein G Jr; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang J; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Skoulidis F; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wu J; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Mehran RJ; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Rice DC; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Walsh GL; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hofstetter WL; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Rajaram R; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Antonoff MB; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Fujimoto J; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Solis LM; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Parra ER; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Haymaker C; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wistuba II; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Swisher SG; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Vaporciyan AA; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lin HY; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wang J; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gibbons DL; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Jack Lee J; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ajami NJ; Platform for Innovative Microbiome and Translational Research (PRIME-TR), Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wargo JA; Platform for Innovative Microbiome and Translational Research (PRIME-TR), Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Allison JP; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sharma P; The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Kadara H; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Heymach JV; Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sepesi B; Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2023 Mar; Vol. 29 (3), pp. 593-604. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1038/s41591-022-02189-0
Abstrakt: Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7-43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6-61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. In patients without known tumor EGFR/ALK alterations, MPR rates were 41.2% (7/17) and 62.5% (10/16) in the Nivo+CT and Ipi+Nivo+CT groups, respectively. No new safety signals were observed in either arm. Single-cell sequencing and multi-platform immune profiling (exploratory endpoints) underscored immune cell populations and phenotypes, including effector memory CD8 + T, B and myeloid cells and markers of tertiary lymphoid structures, that were preferentially increased in the Ipi+Nivo+CT cohort. Baseline fecal microbiota in patients with MPR were enriched with beneficial taxa, such as Akkermansia, and displayed reduced abundance of pro-inflammatory and pathogenic microbes. Neoadjuvant Ipi+Nivo+CT enhances pathologic responses and warrants further study in operable NSCLC. (ClinicalTrials.gov registration: NCT03158129 .).
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: