Original Research Pembrolizumab plus chemotherapy-induced pneumonitis in chemo-nai•ve patients with non-squamous non-small cell lung cancer: A multicentre, retrospective cohort study

被引：28

作者：

Fujimoto, Daichi ^{[1
,2
]}

Miura, Satoru ^{[3
]}

Yoshimura, Kenichi ^{[4
]}

Wakuda, Kazushige ^{[5
]}

Oya, Yuko ^{[6
]}

Yokoyama, Toshihide ^{[7
]}

Yokoi, Takashi ^{[8
]}

Asao, Tetsuhiko ^{[9
]}

Tamiya, Motohiro ^{[10
]}

Nakamura, Atsushi ^{[11
]}

Yoshioka, Hiroshige ^{[12
]}

Haratani, Koji ^{[13
]}

Teraoka, Shunsuke ^{[1
]}

Tokito, Takaaki ^{[14
]}

Murakami, Shuji ^{[15
]}

Tamiya, Akihiro ^{[16
]}

Itoh, Shoichi ^{[17
]}

Yokouchi, Hiroshi ^{[18
]}

Watanabe, Satoshi ^{[19
]}

Yamaguchi, Ou ^{[20
]}

Tomii, Keisuke ^{[2
]}

Yamamoto, Nobuyuki ^{[1
]}

机构：

[1] Wakayama Med Univ, Internal Med 3, Wakayama 6418509, Japan

[2] Kobe City Med Ctr Gen Hosp, Dept Resp Med, Kobe, Hyogo, Japan

[3] Niigata Canc Ctr Hosp, Dept Internal Med, Niigata, Japan

[4] Hiroshima Univ, Med Ctr Translat & Clin Res, Hiroshima Univ Hosp, Hiroshima, Japan

[5] Shizuoka Canc Ctr, Div Thorac Oncol, Shizuoka, Japan

[6] Aichi Canc Ctr Hosp, Dept Thorac Oncol, Nagoya, Aichi, Japan

[7] Kurashiki Cent Hosp, Dept Resp Med, Kurashiki, Okayama, Japan

[8] Hyogo Coll Med, Dept Resp Med & Hematol, Nishinomiya, Hyogo, Japan

[9] Juntendo Univ, Grad Sch Med, Dept Resp Med, Tokyo, Japan

[10] Osaka Int Canc Inst, Dept Thorac Oncol, Osaka, Japan

[11] Sendai Kousei Hosp, Dept Pulm Med, Sendai, Miyagi, Japan

[12] Kansai Med Univ Hosp, Dept Thorac Oncol, Hirakata, Osaka, Japan

[13] Kindai Univ, Dept Med Oncol, Fac Med, Osaka, Japan

[14] Kurume Univ, Div Respirol Neurol & Rheumatol, Dept Internal Med, Sch Med, Kurume, Fukuoka, Japan

[15] Kanagawa Canc Ctr, Dept Thorac Oncol, Yokohama, Kanagawa, Japan

[16] Natl Hosp Org Kinki Chuo Chest Med Ctr, Dept Internal Med, Sakai, Osaka, Japan

[17] Hyogo Canc Ctr, Dept Thorac Oncol, Akashi, Hyogo, Japan

[18] Natl Hosp Org, Dept Resp Med, Hokkaido Canc Ctr, Sapporo, Hokkaido, Japan

[19] Niigata Univ, Dept Resp Med & Infect Dis, Grad Sch Med & Dent Sci, Niigata, Japan

[20] Saitama Med Univ, Dept Resp Med, Comprehens Canc Ctr, Int Med Ctr, Saitama, Japan

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 150卷

关键词：

PD-1; PD-L1; Immune checkpoint inhibitor; Pneumonitis; Pneumonia; Non-small cell lung cancer; ADVERSE EVENTS; RISK-FACTORS; NIVOLUMAB; EFFICACY; DOCETAXEL; SAFETY;

D O I：

10.1016/j.ejca.2021.03.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings. Methods: We conducted a 36-centre, retrospective cohort study in patients with chemo-na & iuml;ve advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019. Results: The study comprised 299 patients. The most frequent grade >3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9-16.7) with all grade pneumonitis and 10 (3.3%, 95% CI 1.6-6.1) with grade >3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4-10.5) and 9 patients (3.0%, 95% CI 1.4-5.6) developed all-grade and grade >3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0-6.8) and 7.5 (95% CI 6.5-8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07-3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12-8.20, P = 0.03). Conclusions: Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy. Trial registration number: UMIN000038084 & ordf; 2021 Elsevier Ltd. All rights reserved.

引用

页码：63 / 72

页数：10

共 28 条

[1] Immortal Time Bias in Observational Studies of Time-to-Event Outcomes: Assessing Effects of Postmastectomy Radiation Therapy Using the National Cancer Database [J].

Agarwal, Parul ;

Moshier, Erin ;

Ru, Meng ;

Ohri, Nisha ;

Ennis, Ronald ;

Rosenzweig, Kenneth ;

Mazumdar, Madhu .

CANCER CONTROL, 2018, 25 (01)

[2]

Akamatsu A, 2018, ANN ONCOL, V29, P431

[3] Barriers to Enrollment in Non-small Cell Lung Cancer Therapeutic Clinical Trials [J].

Baggstrom, Maria Q. ;

Waqar, Saiama N. ;

Sezhiyan, Ananth K. ;

Gilstrap, Eve ;

Gao, Feng ;

Morgensztern, Daniel ;

Govindan, Ramaswamy .

JOURNAL OF THORACIC ONCOLOGY, 2011, 6 (01) :98-102

[4] Molecular analysis of the RET and NTRK1 gene rearrangements in papillary thyroid carcinoma in the Polish population [J].

Brzezianska, Ewa ;

Karbownik, Malgorzata ;

Migdalska-Sek, Monika ;

Pastuszak-Lewandoska, Dorota ;

Wloch, Jan ;

Lewinski, Andrzej .

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2006, 599 (1-2) :26-35

[5] Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: A multicenter retrospective cohort study [J].

Fujimoto, Daichi ;

Yoshioka, Hiroshige ;

Kataoka, Yuki ;

Morimoto, Takeshi ;

Kim, Young Hak ;

Tomii, Keisuke ;

Ishida, Tadashi ;

Hirabayashi, Masataka ;

Hara, Satoshi ;

Ishitoko, Manabu ;

Fukuda, Yasushi ;

Hwang, Moon Hee ;

Sakai, Naoki ;

Fukui, Motonari ;

Nakaji, Hitoshi ;

Morita, Mitsunori ;

Mio, Tadashi ;

Yasuda, Takehiro ;

Sugita, Takakazu ;

Hirai, Toyohiro .

LUNG CANCER, 2018, 119 :14-20

[6] 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

[7] Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non-Small Cell Lung Cancer [J].

Haratani, Koji ;

Hayashi, Hidetoshi ;

Chiba, Yasutaka ;

Kudo, Keita ;

Yonesaka, Kimio ;

Kato, Ryoji ;

Kaneda, Hiroyasu ;

Hasegawa, Yoshikazu ;

Tanaka, Kaoru ;

Takeda, Masayuki ;

Nakagawa, Kazuhiko .

JAMA ONCOLOGY, 2018, 4 (03) :374-378

[8]

HERNA NM, 2018, BMJ-BRIT MED J, V360, pK182, DOI DOI 10.1136/BMJ.K182

[9] Specifying a target trial prevents immortal time bias and other self-inflicted injuries in observational analyses [J].

Hernan, Miguel A. ;

Sauer, Brian C. ;

Hernandez-Diaz, Sonia ;

Platt, Robert ;

Shrier, Ian .

JOURNAL OF CLINICAL EPIDEMIOLOGY, 2016, 79 :70-75

[10] Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available [J].

Hernan, Miguel A. ;

Robins, James M. .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 2016, 183 (08) :758-764

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