The Role of Chemotherapy Plus Immune Checkpoint Inhibitors in Oncogenic-Driven NSCLC: A University of California Lung Cancer Consortium Retrospective Study

被引:10
作者
Benjamin, David J. [1 ,12 ]
Chen, Shuai [2 ]
Eldredge, Joanna B. [3 ]
Schokrpur, Shiruyeh [4 ]
Li, Debory [5 ]
Quan, Zhikuan [2 ]
Chan, Jason W. [6 ]
Cummings, Amy L. [7 ]
Daly, Megan E. [8 ]
Goldman, Jonathan W. [7 ]
Gubens, Matthew A. [9 ]
Harris, Jeremy P. [10 ]
Onaitis, Mark W. [4 ,11 ]
Zhu, Viola W. [1 ,13 ]
Patel, Sandip P. [4 ]
Kelly, Karen [3 ,14 ,15 ]
机构
[1] Univ Calif Irvine, Dept Med, Divs Hematol Oncol, Irvine, CA USA
[2] Univ Calif Davis, Dept Publ Hlth Sci, Div Biostat, Davis, CA USA
[3] Univ Calif Davis, Sch Med, Dept Internal Med, Div Hematol & Oncol, Sacramento, CA USA
[4] Univ Calif San Diego, Sch Med, Dept Med, Div Hematol Oncol, La Jolla, CA USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA
[6] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA
[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA USA
[8] Univ Calif Davis, Sch Med, Dept Radiat Oncol, Sacramento, CA USA
[9] Univ Calif San Francisco, Dept Med, Div Hematol & Oncol, San Francisco, CA USA
[10] Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA USA
[11] Univ Calif San Diego, Dept Surg, Div Cardiothorac Surg, La Jolla, CA USA
[12] Hoag Dr, Bldg 51, Newport Beach, CA USA
[13] Nuvalent, 1 Broadway, 14th Floor, Cambridge, MA USA
[14] 999, 17th St, Suite 200, Denver, CO USA
[15] Int Assoc Study Lung Canc, 999 17th St, Suite 200, Denver, CO 80202 USA
来源
JTO CLINICAL AND RESEARCH REPORTS | 2022年 / 3卷 / 12期
基金
美国国家卫生研究院;
关键词
Driver mutations; Oncogenic driven; Immune checkpoint inhibitors; Chemotherapy; Non-small cell lung cancer; Actionable mutations; PS; 2; NIVOLUMAB; DOCETAXEL;
D O I
10.1016/j.jtocrr.2022.100427
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction: There is a paucity of data on immune checkpoint inhibitors (ICIs) plus doublet chemotherapy (C) in patients with advanced lung cancer whose tumor harbors an actionable mutation. We sought to provide insight into the role of this combination in relation to chemotherapy alone in this patient population.Methods: We conducted a retrospective study at the five University of California National Cancer Institute- designated Comprehensive Cancer Centers. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and significant adverse events. Adverse events in patients who received a tyrosine kinase inhibitor (TKI) post-ICI were also captured. Results: A total of 246 patients were identified, 170 treated with C plus ICI and 76 treated with C alone. Driver alterations included EGFR (54.9%), KRAS (32.9%), ALK (5.3%), HER2/ERBB2 (2.9%), ROS1 (1.2%), MET (1.2%), RET (0.8%), and BRAF non-V600 (0.8%). The overall PFS and OS hazard ratios were not significant at 1.12 (95% confidence interval 0.83-1.51; p = 0.472) and 0.86 (95% confidence interval: 0.60-1.24, p = 0.429), respectively. No significant differences in PFS or OS were observed in the mutational subgroups. Grade 3 or greater adverse events were lower in the C plus ICI group. The multivariate analysis for PFS and OS revealed a performance status (Eastern Cooperative Oncology Group) score of 2, and previous TKI treatment was associated with poorer outcomes with C plus ICI.Conclusions: Our study suggests that patients with oncogenic-driven NSCLC, primarily those with EGFR-driven tumors, treated with a TKI should not subsequently receive C plus ICI. Analysis from prospective clinical trials will provide additional information on the role of ICIs in this group of patients.(c) 2022 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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页数:13
相关论文
共 30 条
[1]   Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors [J].
Akbay, Esra A. ;
Koyama, Shohei ;
Carretero, Julian ;
Altabef, Abigail ;
Tchaicha, Jeremy H. ;
Christensen, Camilla L. ;
Mikse, Oliver R. ;
Cherniack, Andrew D. ;
Beauchamp, Ellen M. ;
Pugh, Trevor J. ;
Wilkerson, Matthew D. ;
Fecci, Peter E. ;
Butaney, Mohit ;
Reibel, Jacob B. ;
Soucheray, Margaret ;
Cohoon, Travis J. ;
Janne, Pasi A. ;
Meyerson, Matthew ;
Hayes, D. Neil ;
Shapiro, Geoffrey I. ;
Shimamura, Takeshi ;
Sholl, Lynette M. ;
Rodig, Scott J. ;
Freeman, Gordon J. ;
Hammerman, Peter S. ;
Dranoff, Glenn ;
Wong, Kwok-Kin .
CANCER DISCOVERY, 2013, 3 (12) :1355-1363
[2]   Targeted therapy in lung cancer: Are we closing the gap in years of life lost? [J].
Benjamin, David J. ;
Haslam, Alyson ;
Gill, Jenny ;
Prasad, Vinay .
CANCER MEDICINE, 2022, 11 (18) :3417-3424
[3]   Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].
Borghaei, H. ;
Paz-Ares, L. ;
Horn, L. ;
Spigel, D. R. ;
Steins, M. ;
Ready, N. E. ;
Chow, L. Q. ;
Vokes, E. E. ;
Felip, E. ;
Holgado, E. ;
Barlesi, F. ;
Kohlhaeufl, M. ;
Arrieta, O. ;
Burgio, M. A. ;
Fayette, J. ;
Lena, H. ;
Poddubskaya, E. ;
Gerber, D. E. ;
Gettinger, S. N. ;
Rudin, C. M. ;
Rizvi, N. ;
Crino, L. ;
Blumenschein, G. R. ;
Antonia, S. J. ;
Dorange, C. ;
Harbison, C. T. ;
Finckenstein, F. Graf ;
Brahmer, J. R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639
[4]   Response to immune checkpoint inhibition as monotherapy or in combination with chemotherapy in metastatic ROS1-rearranged lung cancers. [J].
Choudhury, Noura J. ;
Schneider, Jaime Laurel ;
Patil, Tejas ;
Zhu, Viola Weijia ;
Goldman, Debra A. ;
Yang, Soo-Ryum ;
Falcon, Christina ;
Do, Andrew ;
Nie, Yunan ;
Plodkowski, Andrew J. ;
Chaft, Jamie E. ;
Digumarthy, Subba ;
Rekhtman, Natasha ;
Arcila, Maria E. ;
Iasonos, Alexia ;
Ou, Sai-Hong Ignatius ;
Lin, Jessica Jiyeong ;
Drilon, Alexander E. .
JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (15)
[5]   New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].
Eisenhauer, E. A. ;
Therasse, P. ;
Bogaerts, J. ;
Schwartz, L. H. ;
Sargent, D. ;
Ford, R. ;
Dancey, J. ;
Arbuck, S. ;
Gwyther, S. ;
Mooney, M. ;
Rubinstein, L. ;
Shankar, L. ;
Dodd, L. ;
Kaplan, R. ;
Lacombe, D. ;
Verweij, J. .
EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247
[6]   CheckMate 171: A phase 2 trial of nivolumab in patients with previously treated advanced squamous non-small cell lung cancer, including ECOG PS 2 and elderly populations [J].
Felip, Enriqueta ;
Ardizzoni, Andrea ;
Ciuleanu, Tudor ;
Cobo, Manuel ;
Laktionov, Konstantin ;
Szilasi, Maria ;
Califano, Raffaele ;
Carcereny, Enric ;
Griffiths, Richard ;
Paz-Ares, Luis ;
Duchnowska, Renata ;
Alonso Garcia, Miriam ;
Isla, Dolores ;
Jassem, Jacek ;
Appel, Wiebke ;
Milanowski, Janusz ;
Van Meerbeeck, Jan P. ;
Wolf, Juergen ;
Li, Ang ;
Acevedo, Angelic ;
Popat, Sanjay .
EUROPEAN JOURNAL OF CANCER, 2020, 127 :160-172
[7]  
Gadgeel S, 2019, ANN ONCOL, V30, P64
[8]  
Gadgeel S, 2021, J Thorac Oncol, V16, pS83
[9]   EGFR Mutations and ALK Rearrangements Are Associated with Low Response Rates to PD-1 Pathway Blockade in Non-Small Cell Lung Cancer: A Retrospective Analysis [J].
Gainor, Justin F. ;
Shaw, Alice T. ;
Sequist, Lecia V. ;
Fu, Xiujun ;
Azzoli, Christopher G. ;
Piotrowska, Zofia ;
Huynh, Tiffany G. ;
Zhao, Ling ;
Fulton, Linnea ;
Schultz, Katherine R. ;
Howe, Emily ;
Farago, Anna F. ;
Sullivan, Ryan J. ;
Stone, James R. ;
Digumarthy, Subba ;
Moran, Teresa ;
Hata, Aaron N. ;
Yagi, Yukako ;
Yeap, Beow Y. ;
Engelman, Jeffrey A. ;
Mino-Kenudson, Mari .
CLINICAL CANCER RESEARCH, 2016, 22 (18) :4585-4593
[10]   Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer [J].
Gandhi, L. ;
Rodriguez-Abreu, D. ;
Gadgeel, S. ;
Esteban, E. ;
Felip, E. ;
De Angelis, F. ;
Domine, M. ;
Clingan, P. ;
Hochmair, M. J. ;
Powell, S. F. ;
Cheng, S. Y. -S. ;
Bischoff, H. G. ;
Peled, N. ;
Grossi, F. ;
Jennens, R. R. ;
Reck, M. ;
Hui, R. ;
Garon, E. B. ;
Boyer, M. ;
Rubio-Viqueira, B. ;
Novello, S. ;
Kurata, T. ;
Gray, J. E. ;
Vida, J. ;
Wei, Z. ;
Yang, J. ;
Raftopoulos, H. ;
Pietanza, M. C. ;
Garassino, M. C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (22) :2078-2092