Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

被引：97

作者：

Park, Sehhoon ^{[1
]}

Kim, Tae Min ^{[2
]}

Han, Ji-Youn ^{[3
]}

Lee, Gyeong-Won ^{[4
,5
]}

Shim, Byoung Yong ^{[6
]}

Lee, Yun-Gyoo ^{[7
]}

Kim, Sang-We ^{[8
]}

Kim, Il Hwan ^{[9
]}

Lee, Suee ^{[10
]}

Kim, Yu Jung ^{[11
]}

Park, Ji Hyun ^{[12
]}

Park, Sang-Gon ^{[13
]}

Lee, Ki Hyeong ^{[14
]}

Kang, Eun Joo ^{[15
]}

Kim, Ju Won ^{[16
]}

Shin, Seong-Hoon ^{[17
]}

Ock, Chan-Young ^{[18
]}

Nam, Byung-Ho ^{[19
]}

Lee, Jaebong ^{[20
]}

Jung, Hyun-Ae ^{[1
]}

Sun, Jong-Mu ^{[1
]}

Lee, Se-Hoon ^{[1
]}

Ahn, Jin Seok ^{[1
]}

Ahn, Myung-Ju ^{[1
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hematol Oncol,Dept Med, 81 Irwon Ro, Seoul 06351, South Korea

[2] Seoul Natl Univ, Seoul Natl Univ Hosp, Dept Internal Med, Canc Res Inst, Seoul, South Korea

[3] Natl Canc Ctr, Ctr Lung Canc, Res Inst & Hosp, Goyang Si, Gyeonggi Do, South Korea

[4] Gyeongsang Natl Univ, Gyeongsang Natl Univ Hosp, Inst Hlth Sci, Dept Internal Med,Div Hematol,Coll Med, Jinju, South Korea

[5] Gyeongsang Natl Univ, Gyeongsang Natl Univ Hosp, Inst Hlth Sci, Dept Internal Med,Dept Oncol,Coll Med, Jinju, South Korea

[6] Catholic Univ Korea, Coll Med, Dept Internal Med, Div Med Oncol,St Vincents Hosp, Seoul, South Korea

[7] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Div Hematol & Med Oncol,Dept Internal Med, Seoul, South Korea

[8] Univ Ulsan, Coll Med, Dept Internal Med, Div Oncol,Asan Med Ctr, Seoul, South Korea

[9] Inje Univ, Coll Med, Haeundae Paik Hosp, Div Hematooncol,Dept Internal Med, Busan, South Korea

[10] Dong A Univ, Coll Med, Dept Internal Med, Busan, South Korea

[11] Seoul Natl Univ, Coll Med, Dept Internal Med, Div Hematol & Med Oncol,Bundang Hosp, Seongnam, South Korea

[12] Konkuk Univ, Med Ctr, Sch Med, Dept Hematooncol, Seoul, South Korea

[13] Chosun Univ Hosp, Dept Internal Med, Hematooncol, Gwangju, South Korea

[14] Chungbuk Natl Univ, Chungbuk Natl Univ Hosp, Coll Med, Div Hematol Oncol,Dept Internal Med, Cheongju, South Korea

[15] Korea Univ, Coll Med, Dept Internal Med, Div Hematol Oncol,Guro Hosp, Seoul, South Korea

[16] Korea Univ, Coll Med, Dept Med, Div Hematol Oncol,Anam Hosp, Seoul, South Korea

[17] Kosin Univ, Gospel Hosp, Dept Internal Med, Div Hematooncol, Busan, South Korea

[18] Lunit, Seoul, South Korea

[19] Herings, Seoul, South Korea

[20] Seoul CRO, Seoul, South Korea

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2024年 / 42卷 / 11期

关键词：

D O I：

10.1200/JCO.23.01891

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy. MATERIALS AND METHODS We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). RESULTS A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 >= 1%, >= 10%, and >= 50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm. CONCLUSION To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-mutated NSCLC who have progressed on relevant targeted therapy.

引用

页码：1241 / 1251

页数：24

共 26 条

[1] Brigatinib versus Crizotinib in ALK-Positive Non-Small-Cell Lung Cancer [J].

Camidge, D. R. ;

Kim, H. R. ;

Ahn, M. -J. ;

Yang, J. C. -H. ;

Han, J. -Y. ;

Lee, J. -S. ;

Hochmair, M. J. ;

Li, J. Y. -C. ;

Chang, G. -C. ;

Lee, K. H. ;

Gridelli, C. ;

Delmonte, A. ;

Garcia Campelo, R. ;

Kim, D. -W. ;

Bearz, A. ;

Griesinger, F. ;

Morabito, A. ;

Felip, E. ;

Califano, R. ;

Ghosh, S. ;

Spira, A. ;

Gettinger, S. N. ;

Tiseo, M. ;

Gupta, N. ;

Haney, J. ;

Kerstein, D. ;

Popat, S. .

NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (21) :2027-2039

[2] Combinations of Bevacizumab With Cancer Immunotherapy [J].

Chen, Daniel S. ;

Hurwitz, Herbert .

CANCER JOURNAL, 2018, 24 (04) :193-204

[3] Oncology Meets Immunology: The Cancer-Immunity Cycle [J].

Chen, Daniel S. ;

Mellman, Ira .

IMMUNITY, 2013, 39 (01) :1-10

[4] 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

[5] Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study [J].

Garassino, Marina C. ;

Gadgeel, Shirish ;

Speranza, Giovanna ;

Felip, Enriqueta ;

Esteban, Emilio ;

Domine, Manuel ;

Hochmair, Maximilian J. ;

Powell, Steven F. ;

Bischoff, Helge G. ;

Peled, Nir ;

Grossi, Francesco ;

Jennens, Ross R. ;

Reck, Martin ;

Hui, Rina ;

Garon, Edward B. ;

Kurata, Takayasu ;

Gray, Jhanelle E. ;

Schwarzenberger, Paul ;

Jensen, Erin ;

Pietanza, M. Catherine ;

Rodriguez-Abreu, Delvys .

JOURNAL OF CLINICAL ONCOLOGY, 2023, 41 (11) :1992-+

[6] Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics [J].

Hegde, Priti S. ;

Wallin, Jeffrey J. ;

Mancao, Christoph .

SEMINARS IN CANCER BIOLOGY, 2018, 52 :117-124

[7] Epidermal growth factor receptor mutation enhances expression of vascular endothelial growth factor in lung cancer [J].

Hung, Ming-Szu ;

Chen, I-Chuan ;

Lin, Paul-Yann ;

Lung, Jr-Hau ;

Li, Ya-Chin ;

Lin, Yu-Ching ;

Yang, Cheng-Ta ;

Tsai, Ying-Huang .

ONCOLOGY LETTERS, 2016, 12 (06) :4598-4604

[8] Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer A Meta-Analysis [J].

Lee, Chee Khoon ;

Man, Johnathan ;

Lord, Sally ;

Links, Matthew ;

Gebski, Val ;

Mok, Tony ;

Yang, James Chih-Hsin .

JOURNAL OF THORACIC ONCOLOGY, 2017, 12 (02) :403-407

[9] Sintilimab plus chemotherapy for patients with EGFR- mutated non-squamous non-small-cell lung cancer with disease progression after EGFRtyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double- blind, randomised, placebo-controlled, phase 3 trial [J].

Lu, Shun ;

Wu, Lin ;

Jian, Hong ;

Cheng, Ying ;

Wang, Qiming ;

Fang, Jian ;

Wang, Ziping ;

Hu, Yanping ;

Han, Liang ;

Sun, Meili ;

Miao, Liyun ;

Ding, Cuimin ;

Cui, Jiuwei ;

Wang, Ke ;

Li, Baolan ;

Li, Xingya ;

Ye, Feng ;

Liu, Anwen ;

Pan, Yueyin ;

Cang, Shundong ;

Zhou, Hui ;

Sun, Xing ;

Shen, Yuping ;

Wang, Shuyan ;

Zhang, Wen ;

He, Yue .

LANCET RESPIRATORY MEDICINE, 2023, 11 (07) :624-636

[10] Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3trial [J].