@article{5f04bf18d2814d5f853c3dcd18868fe6,
title = "Neoadjuvant atezolizumab for resectable non-small cell lung cancer: an open-label, single-arm phase II trial",
abstract = "In an ongoing, open-label, single-arm phase II study (NCT02927301), 181 patients with untreated, resectable, stage IB–IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14–28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches.",
author = "{LCMC study investigators} and Chaft, {Jamie E.} and Filiz Oezkan and Kris, {Mark G.} and Bunn, {Paul A.} and Wistuba, {Ignacio I.} and Kwiatkowski, {David J.} and Owen, {Dwight H.} and Yan Tang and Johnson, {Bruce E.} and Lee, {Jay M.} and Gerard Lozanski and Maciej Pietrzak and Michal Seweryn and Byun, {Woo Yul} and Katja Schulze and Alan Nicholas and Ann Johnson and Jessica Grindheim and Stephanie Hilz and Shames, {David S.} and Chris Rivard and Eric Toloza and Haura, {Eric B.} and McNamee, {Ciaran J.} and Patterson, {G. Alexander} and Waqar, {Saiama N.} and Rusch, {Valerie W.} and Carbone, {David P.} and Waqar, {Saiama N.} and Elaine Shum and Misako Nagasaka and Marianna Koczywas and Garon, {Edward B.} and Finley, {David J.} and Camidge, {David R.} and Carlisle, {Jennifer W.} and Blasberg, {Justin D.}",
note = "Funding Information: The authors thank the patients and their families, the study investigators and clinical site staff and the collaborating laboratories for biomarker testing. The authors thank J. Minna, LCMC3 Steering Committee member and consultant. The authors thank R.L. Kitzler and R. Pearson for their contributions to the IMMUNOME analysis. Clinical trial and operations support was provided by E. Brand{\~a}o, Senior Clinical Trial Leader, M. Rocha, Clinical Program Leader, A. Gopalakrishnan, Senior Biosample Operations Manager and A. Stone, Principal Biosample Operations Manager. The LCMC3 study was funded by Genentech. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Ashfield MedComms, an Ashfield Health company and was funded by Genentech. F.O. was supported by the Deutsche Forschungsgemeinschaft (OE698/1–1). Funding Information: J.E.C. serves as an advisor to Genentech/Roche, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb, Flame Biosciences, Janssen Oncology, Guardant Health, Regeneron/Sanofi and Novartis. She reports research funding from Genentech/Roche, Bristol Myers Squibb, AstraZeneca/MedImmune, Novartis and Merck. F.O. reports honoraria from Novartis, serves as an advisor to Epigenomics, Sanofi-Aventis and Decibio and has received travel, accommodations and expenses from Genentech/Roche and research funding (paid to her institution) from Genentech/Roche. M.G.K. reports speaking fees from AstraZeneca and Pfizer, consultant fees from Janssen and in-kind support for medical writing from Hoffman La Roche. P.A.B. is on advisory or data safety monitoring boards for Bristol Myers Squibb and Merck and reports membership on the Board of Directors for Verastem, with funding paid to his institution. I.I.W. reports grants and personal fees from Genentech/Roche, Bayer, Bristol Myers Squibb, AstraZeneca, Pfizer, HTG Molecular, GlaxoSmithKline, Guardant Health, Merck, Novartis, Sanofi and Amgen; personal fees from Asuragen, Flame, Daiichi Sankyo, Oncocyte, MSD and Platform Health; and grants from Adaptive, Adaptimmune, EMD Serono, Takeda, Karus, Johnson & Johnson, 4D, Iovance and Akoya, outside of the submitted work. D.J.K. serves as an advisor to AstraZeneca and Genentech/Roche and reports research funding from AADi, Genentech and Revolution Medicines. D.H.O. reports funding (paid to his institution) from Genentech, Merck, Pfizer, Palobiofarma and Bristol Myers Squibb. Y.T. reports no relationships to disclose. B.E.J. reports consultant fees from Checkpoint Therapeutics, Genentech, Hummingbird Diagnostics and Hengrui Therapeutics. J.M.L. reports grants, consulting fees and honoraria from AstraZeneca, Bristol Myers Squibb, Genentech and Novartis and leadership roles at AstraZeneca, Genentech and Novartis. G.L. reports research funding from Genentech, Innate Pharma, Novartis and Stemline Therapeutics. M.P. reports no relationships to disclose. M.S. reports no relationships to disclose. W.Y.B. reports no relationships to disclose. K.S. is an employee of Genentech and reports stock ownership with Roche. A.N. is an employee of Genentech and reports stock ownership with Roche. A.J. is an employee of Genentech and reports stock ownership with Roche. J.G. is an employee of Genentech and reports stock ownership with Roche. S.H. is an employee of Genentech and reports stock ownership with Roche. D.S. is an employee of Genentech and reports stock ownership with Roche. C.R. reports no relationships to disclose. E.T. reports honoraria from Intuitive Surgical. E.B.H. serves in a consulting or advisory role to Amgen, Ellipses Pharma, Janssen Oncology, Janssen Research & Development and Revolution Medicines; reports research funding (paid to his institution) from AstraZeneca, Genentech, Incyte, Janssen, Novartis, Revolution Medicines and Spectrum Pharmaceuticals; and reports patents, royalties or other intellectual property from Protein–Protein Interactions as Biomarkers Patent. C.J.M. reports no relationships to disclose. G.A.P. reports no relationships to disclose. S.N.W. reports research support grants from AbbVie, Ariad Pharmaceuticals, Genentech, Immunomedics, Millennium Pharmaceuticals, Roche, Astellas Pharma, Daiichi Sankyo, Cullinan Pearl, Verastem, GlaxoSmithKline/GSK, Janssen Research & Development, Elevation Oncology, Genentech, Loxo Oncology, Takeda Pharmaceuticals Company Limited and the SWOG Clinical Trials Partnership; has received honoraria from the American Society of Clinical Oncology; and serves as Chair of the Data Safety Monitoring Board for the Hoosier Cancer Research Network. V.W.R. is a member of the Data Safety and Monitoring Committee for the MARS2 trial (UK) and serves as Co-Chair of the National Cancer Institute Thoracic Staging Malignancy Committee. She reports funding (paid to her institution) from Genentech. D.P.C. serves in a consultant or advisory role to AbbVie, Agenus, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, EMD Serono, Genentech/Roche, Helsinn Healthcare, Incyte, Inivata, Inovio Pharmaceuticals, Janssen, Kyowa Hakko Kirin, Merck, Novartis, Pfizer, prIME Oncology and Takeda and research funding from Bristol Myers Squibb and Genentech. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = oct,
doi = "10.1038/s41591-022-01962-5",
language = "English",
volume = "28",
pages = "2155--2161",
journal = "Nature medicine",
issn = "1078-8956",
number = "10",
}