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Prediction of patients with a tumor proportion score > 50% who do not respond to first-line monotherapy with pembrolizumab

Authors
  • Morita, Mitsunori1
  • Tamiya, Motohiro2
  • Fujimoto, Daichi3
  • Tamiya, Akihiro4
  • Suzuki, Hidekazu5
  • Hirano, Katsuya6
  • Fukuda, Yasushi7
  • Yokoyama, Toshihide7
  • Kominami, Ryota8
  • Kanazu, Masaki9
  • Uchida, Junji10
  • Hara, Satoshi11
  • Yamashita, Shuji1
  • Tomioka, Hiromi1
  • 1 Department of Respiratory Medicine, Kobe City Medical Center West Hospital, 2-4, Ichiban-cho, Nagata-ku, Kobe-shi, Hyogo, 653-0013, Japan , Kobe-shi (Japan)
  • 2 Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka, 541-8567, Japan , Osaka (Japan)
  • 3 Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminamimachi, Chuo-ku, Kobe-shi, Hyogo, 650-0047, Japan , Kobe-shi (Japan)
  • 4 National Hospital Organization Kinki-Chuo Chest Medical Center, 1180, Nagasone-cho, Kita-ku, Sakai-shi, Osaka, 591-8555, Japan , Osaka (Japan)
  • 5 Osaka Habikino Medical Center, 3-7-1, Habikino, Habikino-shi, Osaka, 583-8588, Japan , Osaka (Japan)
  • 6 Hyogo Prefectural Amagasaki General Medical Center, 2-17-77, Higashi-Naniwa-Cho, Amagasaki-shi, Hyogo, 660-8550, Japan , Amagasaki-shi (Japan)
  • 7 Kurashiki Central Hospital, 1-1-1, Miwa, Kurashiki-shi, Okayama, 710-8602, Japan , Okayama (Japan)
  • 8 National Hospital Organization Himeji Medical Center, 68, Honmachi, Himeji-shi, Hyogo, 670-8520, Japan , Himeji-shi (Japan)
  • 9 National Hospital Organization Osaka Toneyama Medical Center, 5-1-1, Toneyama, Toyonaka-shi, Osaka, 560-0045, Japan , Osaka (Japan)
  • 10 Osaka General Medical Center, 3-1-56, Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan , Osaka (Japan)
  • 11 Itami City Hospital, 1-100, Koyaike, Itami-shi, Hyogo, 664-8540, Japan , Itami-shi (Japan)
Type
Published Article
Journal
BMC Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Feb 03, 2020
Volume
20
Issue
1
Identifiers
DOI: 10.1186/s12885-020-6582-4
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundPembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50% [1]. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown.MethodsWe retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) > 50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data.ResultsA total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N = 52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥ 2 (p = 0.0832), stage IV disease or recurrence (p = 0.0487), PD-L1 TPS 50–89% (p = 0.0657), use of steroids prior to the administration of pembrolizumab (p = 0.0243), malignant pleural effusion (p = 0.0032), and baseline C-reactive protein (CRP) levels > 1.0 mg/dL (p = 0.0390) were significantly associated with non-response to treatment.In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p = 0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p = 0.0228), and baseline CRP > 1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p = 0.0402) were significantly associated with non-response to treatment.ConclusionIn real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels > 1.0 mg/dL reduced the response of first-line monotherapy with pembrolizumab.

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