DOI QR코드

DOI QR Code

상급종합병원 암센터에서 Nivolumab 사용평가와 치료성과에 미치는 영향인자

Evaluation of Nivolumab Use and Factors related to Treatment Outcomes in a Cancer Center of a Top Tier General Hospital

  • 엄고혜 (이화여자대학교 임상보건융합대학원) ;
  • 조윤숙 (서울대학교병원 약제부) ;
  • 이정연 (이화여자대학교 임상보건융합대학원)
  • Eoum, Gohye (Graduate School of Converging Clinical and Public Health, Ewha Womans University) ;
  • Cho, Yoonsook (Department of Pharmacy, Seoul National University Hospital) ;
  • Rhie, Sandy Jeong (Graduate School of Converging Clinical and Public Health, Ewha Womans University)
  • 투고 : 2018.06.02
  • 심사 : 2018.06.18
  • 발행 : 2018.06.29

초록

Background: We strived to evaluate the status of nivolumab use and associated factors on the clinical efficacy of the drug. Methods: The study was retrospectively conducted in patients who had been administered nivolumab at least once at the cancer center of Seoul National University Hospital from June 2015 to April 2017. Data were collected from electronic medical records. A medication-use evaluation was performed based on the American Society of Health-System Pharmacists mediation-use guidelines. Results: Sixty-six of the 74 patients (89.2%) showed indications approved for nivolumab use by the Korean Ministry of Food and Drug Safety (MFDS; n=55) or the US Food and Drug Administration (FDA; n=11). Approximately 73.0% of the patients were administered the approved dose of 3 mg/kg but 25.7% were administered an unapproved fixed dose of 100 mg. The overall response rate was 21.7%, and the response rate of non-small cell lung cancer patients, who accounted for the largest number of indications, was 18.8%. Adverse reactions were found in 90.1% of the patients and were mostly mild (86%). The expression of programmed death-ligand 1 (PD-L1) was analyzed as a factor affecting treatment response (p=0.028, odds ratio [OR]=11.331). Conclusion: PD-L1 expression was found to affect treatment response. However, caution is required while using an unapproved dosage and in the absence of monitoring for effectiveness and safety. Therefore, an effective protocol or instruction manual for the proper use of nivolumab should be considered.

키워드

참고문헌

  1. Robert C, Long GV, Brady B, et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. N Engl J Med 2015;372:320-30. https://doi.org/10.1056/NEJMoa1412082
  2. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med 2015;373:123-35. https://doi.org/10.1056/NEJMoa1504627
  3. Borghaei H, Paz-Ares L, Horn L et al. Nivolumab versus Docetaxel in Advanced Non squamous Non-Small-Cell Lung Cancer. N Engl J Med 2015; 373:1627-39. https://doi.org/10.1056/NEJMoa1507643
  4. Motzer RJ, Escudier B, McDermott DF et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med 2015;373:1803-13. https://doi.org/10.1056/NEJMoa1510665
  5. Ferris RL, Blumenschein G, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med 2016;375:1856-67. https://doi.org/10.1056/NEJMoa1602252
  6. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin's Lymphoma. N Engl J Med 2015;372:311-9. https://doi.org/10.1056/NEJMoa1411087
  7. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicenter, single-arm, phase 2 trial. Lancet Oncol 2017;18(3):312-22. https://doi.org/10.1016/S1470-2045(17)30065-7
  8. Ministry of Food and Drug Safety. 2016 Medication approval report. Available from http://www.mfds.go.kr/index.do?mid=695&pageNo=1&seq=27418&cmd=v. Accessed April 13, 2017
  9. Naidoo J, Page DB, Li BT, et al. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann. Oncol 2015;26: 2375-91.
  10. American Society of Health-System Pharmacists. ASHP guidelines on medication-use evaluation. Am J Health-Syst Pharm 1996; 53:1953-5.
  11. Opdivo(R) Intravenous injection (Nivolumab, recombinant). Ministry of Food and Drug Safety; 2016.5 Available from https://www.mfds.go.kr/. Accessed April 13, 2017.
  12. Opdivo(R) [package insert]. Princeton, NJ: Bristol-Myers Squibb; Available from https://packageinserts.bms.com/pi/pi_opdivo.pdf. Accessed February 23, 2017.
  13. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Available from https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-_QuickReference_5x7.pdf. Accessed May 25, 2017.
  14. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366: 2455-65. https://doi.org/10.1056/NEJMoa1200694
  15. Agrawal S, Feng Y, Roy A, et al. Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy. J Immunother Cancer 2016; 4:72-82. https://doi.org/10.1186/s40425-016-0177-2
  16. Christian G, Simon G, Richard E, et al. Hyponatremia as an unrecognized risk factor in non-small cell lung cancer (NSCLC) treatment with nivolumab. J Clin Oncol 2017;35:suppl; abstr e14526.
  17. Kumar V, Chaudhary N, Garg M, et al. Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy. Front Pharmacol 2017;8:311.
  18. James L, Katy K, Alain P, et al. Relationship between liver metastases and PD1 blockade in melanoma. J Clin Oncol 2017; 35:suppl; abstr 3072.
  19. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2016; 375:1823-33. https://doi.org/10.1056/NEJMoa1606774

피인용 문헌

  1. 고령 암환자에서의 nivolumab과 pembrolizumab의 유효성과 안전성 평가 vol.30, pp.1, 2020, https://doi.org/10.24304/kjcp.2020.30.1.11
  2. Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer vol.14, pp.5, 2018, https://doi.org/10.3390/ph14050445