DOI QR코드

DOI QR Code

Evaluation of Efficacy and Safety of Nivolumab and Pembrolizumab in Elderly Cancer Patients

고령 암환자에서의 nivolumab과 pembrolizumab의 유효성과 안전성 평가

  • 김혜성 (차의과학대학교 임상약학대학원) ;
  • 정효근 (보훈공단 중앙보훈병원 약제실) ;
  • 심미경 (차의과학대학교 임상약학대학원)
  • Received : 2019.08.09
  • Accepted : 2020.02.26
  • Published : 2020.03.31

Abstract

Background: Nivolumab and pembrolizumab are antagonists of the programmed death-ligand 1 (PD-L1) receptor that function as immuno-oncological agents. This study aimed to evaluate the safety and efficacy of nivolumab and pembrolizumab in elderly patients in outpatient settings. Methods: The safety and efficacy of nivolumab and pembrolizumab were compared retrospectively among patients at the Veterans Health Service (VHS) Medical Center in Seoul, South Korea, from September 1, 2017 to August 25, 2018. Results: Eighty-seven patients were selected for the study. The median progression-free survival was 63 days for nivolumab (95% confidence interval (CI), [14 to 282]) vs. 243 days for pembrolizumab (95% CI, [22 to 348]) (p =0.04). The objective response rate (ORR) was 0% in the nivolumab group vs 5.6% in the pembrolizumab group (p =0.310). All the patients exhibited treatment-related adverse effects. More than 89% of the patients exhibited diseases of the gastrointestinal (GI) tract. Pneumonia, of grades three or higher, was the most common adverse effect, followed by weakness and anorexia. Conclusions: There was no statistically significant difference between the nivolumab group and the pembrolizumab group with respect to the ORR. The incidence and severity of the adverse effects in this study were higher than those of previous studies; however, these adverse effects are generally manageable in a real-world clinical setting. Further randomized controlled studies will be necessary to confirm these results in elderly patients.

Keywords

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. Cancer J Clin 2018;68:7-30. https://doi.org/10.3322/caac.21442
  2. Jung KW, Won YJ, Kong HJ, Lee ES. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2016. Cancer Res Treat 2019;51(2):417-430. https://doi.org/10.4143/crt.2019.138
  3. Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 2016;54:139-48. https://doi.org/10.1016/j.ejca.2015.11.016
  4. Eoum G, Cho Y, Rhie SJ. Evaluation of nivolumab use and factors related to treatment outcomes in a cancer center of a top tier general hospital. Korean J Clin Pharm 2018;28:88-94. https://doi.org/10.24304/kjcp.2018.28.2.88
  5. Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to,or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12,ATTRACTION-2): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;390:2461-71. https://doi.org/10.1016/S0140-6736(17)31827-5
  6. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE 010): a randomized controlled trial. Lancet 2016;387:1540-50. https://doi.org/10.1016/s0140-6736(15)01281-7
  7. Montecino-Rodriguez E, Berent-Maoz B, Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest 2013;123:958-65. https://doi.org/10.1172/JCI64096
  8. Hao C, Tian J, Liu H, Li F, Niu H, Zhu B. Efficacy and safety of anti-PD-1 and anti-PD-1 combined with anti-CTLA-4 immunotherapy to advanced melanoma: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2017;96(26):e7325. https://doi.org/10.1097/md.0000000000007325
  9. Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer. 2017;123(11):1904-11. https://doi.org/10.1002/cncr.30642
  10. Kanesvaran R, Cordoba R, Maggiore R. Immunotherapy in older adults with advanced cancers: implications for clinical decisionmaking and future research. Am Soc Clin Oncol Educ Book 2018;38:400-14. https://doi.org/10.1200/EDBK_201435
  11. Health insurance review & assessment service. Question and answer for medical care application of immune checkpoint inhibitors, nivolumab and pembrolizumab. Available from https://www.hira.or.kr/bbsDummy.do?pgmid=HIRAA030023080000&brdScnBltNo=4&brdBltNo=45624#none. Accessed August 25th, 2019
  12. Passiglia F, Galvano A, Rizzo S, et al. Looking for the best immunecheckpoint inhibitor in pre-treated NSCLC patients: An indirect comparison between nivolumab, pembrolizumab and atezolizumab. Int J Cancer 2018;142(6):1277-84. https://doi.org/10.1002/ijc.31136
  13. Ellis PM, Vella ET, Ung YC. Immune checkpoint inhibitors for patients with advanced non-small-cell lung cancer: A systematic review. Clin Lung Cancer 2017;18(5):444-59. https://doi.org/10.1016/j.cllc.2017.02.001
  14. Yan tie, Xuelei Ma, Chenjing Zhu, et al. Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Int J Cancer 2017;140:948-958. https://doi.org/10.1002/ijc.30501
  15. Wang M, Ma X, Guo L, Xia f. Safety and efficacy profile of pembrolizumab in solid cancer: pooled reanalysis based on randomized controlled trials. Drug Des Devel Ther 2017;11: 2851-60. https://doi.org/10.2147/DDDT.S146286
  16. 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