Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation-positive non-small-cell lung cancer in a real-world setting (OSI-FACT)

被引：64

作者：

Sakata, Yoshihiko ^{[1
]}

Sakata, Shinya ^{[2
]}

Oya, Yuko ^{[3
]}

Tamiya, Motohiro ^{[4
]}

Suzuki, Hidekazu ^{[5
]}

Shibaki, Ryota ^{[6
]}

Okada, Asuka ^{[7
]}

Kobe, Hiroshi ^{[8
]}

Matsumoto, Hirotaka ^{[9
]}

Yokoi, Takashi ^{[10
]}

Sato, Yuki ^{[11
]}

Uenami, Takeshi ^{[12
]}

Saito, Go ^{[13
]}

Tsukita, Yoko ^{[14
]}

Inaba, Megumi ^{[15
]}

Ikeda, Hideki ^{[13
,16
]}

Arai, Daisuke ^{[17
]}

Maruyama, Hirotaka ^{[18
]}

Hara, Satoshi ^{[19
]}

Tsumura, Shinsuke ^{[20
]}

Morinaga, Jun ^{[21
]}

Sakagami, Takuro ^{[2
]}

机构：

[1] Saiseikai Kumamoto Hosp, Div Resp Med, Minami Ku, 5-3-1 Chikami, Kumamoto, Kumamoto 8614193, Japan

[2] Kumamoto Univ Hosp, Dept Resp Med, Chuo Ku, 1-1-1 Honjo, Kumamoto, Kumamoto 8608556, Japan

[3] Aichi Canc Ctr Hosp, Dept Thorac Oncol, Chikusa Ku, 1-1 Kanokoden, Nagoya, Aichi 4648681, Japan

[4] Osaka Int Canc Inst, Dept Thorac Oncol, Chuo Ku, 3-1-69 Otemae, Osaka, Osaka 5418567, Japan

[5] Osaka Habikino Med Ctr, Dept Thorac Oncol, 3-7-1 Habikino, Osaka 5838588, Japan

[6] Wakayama Med Univ, Internal Med 3, 811-1 Kimiidera, Wakayama, Wakayama 6418509, Japan

[7] Osaka City Gen Hosp, Dept Med Oncol, Miyakojima Ku, 2-13-22 Miyakojima Hondori, Osaka, Osaka 5310021, Japan

[8] Kurashiki Cent Hosp, Dept Resp Med, 1-1-1 Miwa, Kurashiki, Okayama 7108602, Japan

[9] Hyogo Prefectural Amagasaki Gen Med Ctr, Dept Resp Med, 2-17-77 Higashinaniwa, Amagasaki, Hyogo 6608550, Japan

[10] Hyogo Coll Med, Dept Thorac Oncol, 1-1 Mukogawa, Nishinomiya, Hyogo 6638501, Japan

[11] Kobe City Med Ctr Gen Hosp, Dept Resp Med, Chuo Ku, 2-1-1 Minatojimaminami, Kobe, Hyogo 6500047, Japan

[12] Natl Hosp Org Osaka Toneyama Med Ctr, Dept Thorac Oncol, 5-1-1 Toneyama, Osaka, Osaka 5608552, Japan

[13] Chiba Univ, Grad Sch Med, Dept Respirol, Chuo Ku, 1-8-1 Inohana, Chiba, Chiba 2608670, Japan

[14] Tohoku Univ, Dept Resp Med, Grad Sch Med, Aoba Ku, 2-1 Seiryo, Sendai, Miyagi 9808575, Japan

[15] Kumamoto City Hosp, Div Resp Med, Minami Ku, 1-5-1 Tainoshima, Kumamoto, Kumamoto 8620965, Japan

[16] Kimitsu Chuo Hosp, Dept Resp Med, Kisarazu, 1010 Sakurai, Kisarazu, Chiba 2928535, Japan

[17] Saiseikai Utsunomiya Hosp, Dept Internal Med, 911-1 Takebayashi, Utsunomiya, Tochigi 3210974, Japan

[18] Japan Org Occupat Hlth & Safety, Dept Resp Med, Kumamoto Rosai Hosp, 1670 Takehara, Yatsushiro, Kumamoto 8668533, Japan

[19] Itami City Hosp, Dept Resp Med, 1-100 Koyaike, Itami, Hyogo 6648540, Japan

[20] Kumamoto Reg Med Ctr, Dept Resp Med, Chuo Ku, 5-16-10 Honjyo, Kumamoto, Kumamoto 8600811, Japan

[21] Kumamoto Univ Hosp, Dept Clin Invest Biostat, Chuo Ku, 1-1-1 Honjo, Kumamoto, Kumamoto 8608556, Japan

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 159卷

关键词：

Non-small-cell lung cancer; EGFR mutation; Osimertinib; Multicentre study; Progression-free survival; Multivariate analysis; Adverse events; Pneumonitis; Discontinuation; Real-world; OPEN-LABEL; CHEMOTHERAPY; MULTICENTER; EXPRESSION; GEFITINIB; ERLOTINIB;

D O I：

10.1016/j.ejca.2021.09.041

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Osimertinib is the standard of care in the initial treatment for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer. However, clinical data and reliable prognostic biomarkers are insufficient. Methods: We performed a retrospective multicentre cohort study for 538 EGFR mutation-positive patients, who received osimertinib as the initial treatment between August 2018 and December 2019. The main outcome was progression-free survival (PFS). Results: The median observation period was 14.7 months (interquartile range 11.4-20.0). The median PFS was 20.5 months (95% confidence interval [CI] 18.6-not reached). Multivariate analysis showed that sex (male) (hazard ratio [HR] 1.99, 95% CI 1.35-2.93, P = 0.001), malignant effusions (HR 1.51, 95% CI 1.11-2.04, P = 0.008), liver metastasis (HR 1.55, 95% CI 1.03-2.33, P = 0.037), advanced unresectable cases (HR 1.71, 95% CI, 1.04-2. 82, P = 0.036), mutation type and programmed cell death-ligand 1 (PD-L1) expression were associated with PFS. The L858R (HR 1.55, 95% CI 1.01-2.38, P = 0.043) and uncommon mutations (HR 3.15, 95% CI 1.70-5.83, P < 0.001) were associated with PFS. PD-L1 expression of 1-49% (HR 1.66, 95% CI 1.05-2.63, P = 0.029), >50% (HR 2.24, 95% CI 1.17-4.30, P = 0.015) and unknown (HR 1.53, 95% CI 1.05-2.22, P = 0.026) was associated with PFS. The main reasons for treatment discontinuation among 219 patients were disease progression (44.3%), pneumonitis (25.5%) and other adverse events (16.0%). Conclusion: During initial treatment with osimertinib, PD-L 1 expression is significantly related to PFS. Adverse events are a noteworthy reason for discontinuation. (c) 2021 Elsevier Ltd. All rights reserved.

引用

页码：144 / 153

页数：10

共 27 条

[1] Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA [J].

Brown, Helen ;

Vansteenkiste, Johan ;

Nakagawa, Kazuhiko ;

Cobo, Manuel ;

John, Thomas ;

Barker, Craig ;

Kohlmann, Alexander ;

Todd, Alexander ;

Saggese, Matilde ;

Chmielecki, Juliann ;

Markovets, Aleksandra ;

Scott, Marietta ;

Ramalingam, Suresh S. .

JOURNAL OF THORACIC ONCOLOGY, 2020, 15 (01) :138-143

[2] Osimertinib for Patients With Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Multicenter, Open-Label, Phase II Trial (KCSG-LU15-09) [J].

Cho, Jang Ho ;

Lim, Sung Hee ;

An, Ho Jung ;

Kim, Ki Hwan ;

Park, Keon Uk ;

Kang, Eun Joo ;

Choi, Yoon Hee ;

Ahn, Mi Sun ;

Lee, Myung Hee ;

Sun, Jong-Mu ;

Lee, Se-Hoon ;

Ahn, Jin Seok ;

Park, Keunchil ;

Ahn, Myung-Ju .

JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (05)

[3] PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients [J].

D'Incecco, A. ;

Andreozzi, M. ;

Ludovini, V. ;

Rossi, E. ;

Capodanno, A. ;

Landi, L. ;

Tibaldi, C. ;

Minuti, G. ;

Salvini, J. ;

Coppi, E. ;

Chella, A. ;

Fontanini, G. ;

Filice, M. E. ;

Tornillo, L. ;

Incensati, R. M. ;

Sani, S. ;

Crino, L. ;

Terracciano, L. ;

Cappuzzo, F. .

BRITISH JOURNAL OF CANCER, 2015, 112 (01) :95-102

[4] Prognostic Value of the Lung Immune Prognostic Index for Patients Treated for Metastatic Non-Small Cell Lung Cancer [J].

Kazandjian, Dickran ;

Gong, Yutao ;

Keegan, Patricia ;

Pazdur, Richard ;

Blumenthal, Gideon M. .

JAMA ONCOLOGY, 2019, 5 (10) :1481-1485

[5] Hippo effector YAP directly regulates the expression of PD-L1 transcripts in EGFR-TKI-resistant lung adenocarcilloma [J].

Lee, Byung Soo ;

Park, Dong Il ;

Lee, Da Hye ;

Lee, Jeong Eun ;

Yeo, Min-kyung ;

Park, Yeon Hee ;

Lim, Dae Sik ;

Choi, Wonyoung ;

Lee, Da Hye ;

Yoo, Geon ;

Kim, Han-byul ;

Kang, Dahyun ;

Moon, Jae Young ;

Jung, Sung Soo ;

Kim, Ju Ock ;

Cho, Sang Yeon ;

Park, Hee Sun ;

Chung, Chaeuk .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2017, 491 (02) :493-499

[6] 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

[7] Relationship between PD-L1 expression and outcome in EGFR-mutant lung cancer patients treated with EGFR tyrosine kinase inhibitors [J].

Liu, Jia ;

Itchins, Malinda ;

Nagrial, Adnan ;

Cooper, Wendy A. ;

De Silva, Madhawa ;

Barnet, Megan ;

Varikatt, Winny ;

Sivasubramaniam, Vanathi ;

Davis, Alexander ;

Gill, Anthony J. ;

Blinman, Prunella ;

Lee, Kenneth ;

Hui, Rina ;

Gao, Bo ;

Pavlakis, Nick ;

Clarke, Stephen ;

Lee, Jenny ;

Boyer, Michael ;

Kao, Steven .

LUNG CANCER, 2021, 155 :28-33

[8] Gefitinib or Chemotherapy for Non-Small-Cell Lung Cancer with Mutated EGFR. [J].

Maemondo, Makoto ;

Inoue, Akira ;

Kobayashi, Kunihiko ;

Sugawara, Shunichi ;

Oizumi, Satoshi ;

Isobe, Hiroshi ;

Gemma, Akihiko ;

Harada, Masao ;

Yoshizawa, Hirohisa ;

Kinoshita, Ichiro ;

Fujita, Yuka ;

Okinaga, Shoji ;

Hirano, Haruto ;

Yoshimori, Kozo ;

Harada, Toshiyuki ;

Ogura, Takashi ;

Ando, Masahiro ;

Miyazawa, Hitoshi ;

Tanaka, Tomoaki ;

Saijo, Yasuo ;

Hagiwara, Koichi ;

Morita, Satoshi ;

Nukiwa, Toshihiro .

NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (25) :2380-2388

[9] Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry [J].

Mazieres, J. ;

Drilon, A. ;

Lusque, A. ;

Mhanna, L. ;

Cortot, A. B. ;

Mezquita, L. ;

Thai, A. A. ;

Mascaux, C. ;

Couraud, S. ;

Veillon, R. ;

Van Den Heuvel, M. ;

Neal, J. ;

Peled, N. ;

Fruh, M. ;

Ng, T. L. ;

Gounant, V ;

Popat, S. ;

Diebold, J. ;

Sabari, J. ;

Zhu, V. W. ;

Rothschild, S. I. ;

Bironzo, P. ;

Martinez-Marti, A. ;

Curioni-Fontecedro, A. ;

Rosell, R. ;

Lattuca-Truc, M. ;

Wiesweg, M. ;

Besse, B. ;

Solomon, B. ;

Barlesi, F. ;

Schouten, R. D. ;

Wakelee, H. ;

Camidge, D. R. ;

Zalcman, G. ;

Novello, S. ;

Ou, S. I. ;

Milia, J. ;

Gautschi, O. .

ANNALS OF ONCOLOGY, 2019, 30 (08) :1321-1328

[10] Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer [J].

Mok, T. S. ;

Wu, Y. -L. ;

Ahn, M. -J. ;

Garassino, M. C. ;

Kim, H. R. ;

Ramalingam, S. S. ;

Shepherd, F. A. ;

He, Y. ;

Akamatsu, H. ;

Theelen, W. S. M. E. ;

Lee, C. K. ;

Sebastian, M. ;

Templeton, A. ;

Mann, H. ;

Marotti, M. ;

Ghiorghiu, S. ;

Papadimitrakopoulou, V. A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2017, 376 (07) :629-640

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