Download PDF
CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2020; 41(03): 393-396
DOI: 10.4103/ijmpo.ijmpo_37_20
Drug Review

Pembrolizumab: The Nut Cracker

Gangothri Selvarajan
Department of Medical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
› Author Affiliations Financial support and sponsorship Nil.
› Further Information
   Permissions and Reprints

Abstract

Anti-programmed cell death-1 (PD-1)/PD ligand-1 immune checkpoint inhibitors (ICIs) are the newest class of drugs approved for various advanced cancers. Pembrolizumab, an anti-PD1 inhibitor, is approved for treating advanced-stage solid malignancies and refractory lymphomas. Recently, it has been approved as tumor agnostic therapy for microsatellite instability-high advanced-stage disease. In all these studies, pembrolizumab has shown dramatic efficacy with lesser Grade3/4 immune-related adverse events. Contemporarily, immunotherapy paved the way for diagnostic assays and immunotherapy-related response assessment criteria definitions. No published Indian experience with ICIs exists other than isolated case reports. This article aims to review on pembrolizumab mechanism, its indications, and safety. The description of other ICIs is beyond the scope of this review.

Keywords

Advanced stage solid cancers - immune checkpoint inhibitors - lymphomas - pembrolizumab


Publication History

Received: 01 February 2020

Accepted: 09 June 2020

Article published online:
28 June 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Oiseth SJ, Aziz MS. Cancer immunotherapy: A brief review of the history, possibilities, and challenges ahead. J Cancer Metastasis Treat 2017; 3: 250-61
    CrossrefGoogle Scholar
  • 2 O'Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol 2019; 16: 151-67
    CrossrefPubMedGoogle Scholar
  • 3 Johnson DB, Peng C, Sosman JA. Nivolumab in melanoma: Latest evidence and clinical potential. Ther Adv Med Oncol 2015; 7: 97-106
    CrossrefPubMedGoogle Scholar
  • 4 Borrie AE, Maleki Vareki S. T lymphocyte-based cancer immunotherapeutics. Int Rev Cell Mol Biol 2018; 341: 201-76
    CrossrefPubMedGoogle Scholar
  • 5 Duan J, Cui L, Zhao X, Bai H, Cai S, Wang G. et al. Use of immunotherapy with programmed cell death 1 vs programmed cell death ligand 1 inhibitors in patients with cancer: A systematic review and meta-analysis. JAMA Oncol 2019; 6: 375-84
    CrossrefPubMedGoogle Scholar
  • 6 Traila A, Dima D, Achimas-Cadariu P, Micu R. Fertility preservation in Hodgkin's lymphoma patients that undergo targeted molecular therapies: An important step forward from the chemotherapy era. Cancer Manag Res 2018; 10: 1517-26
    CrossrefPubMedGoogle Scholar
  • 7 Ellinger I, Fuchs R. HFcRn-mediated transplacental immunoglobulin G transport: Protection of and threat to the human fetus and newborn. Wien Med Wochenschr 2012; 162: 207-13
    CrossrefPubMedGoogle Scholar
  • 8 Heinzerling L, Goldinger SM. A review of serious adverse effects under treatment with checkpoint inhibitors. Curr Opin Oncol 2017; 29: 136-44
    CrossrefPubMedGoogle Scholar
  • 9 Li Z, Song W, Rubinstein M, Liu D. Recent updates in cancer immunotherapy: A comprehensive review and perspective of the 2018 China cancer immunotherapy workshop in Beijing. J Hematol Oncol 2018; 11: 142
    CrossrefPubMedGoogle Scholar
  • 10 Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP. et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: Results from the phase II Keynote158 study. J Clin Oncol 2020; 38: 1-10
    CrossrefPubMedGoogle Scholar
  • 11 Balar AV, Kulkarni GS, Uchio EM, Boormans J, Moure L, Krieger LEM. et al Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG). J Clin Oncol 2019; 37: 350
    CrossrefPubMedGoogle Scholar
  • 12 Cohen EE, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ. et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 2019; 7: 184
    CrossrefPubMedGoogle Scholar
  • 13 Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D. et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019; 380: 1116-27
    CrossrefPubMedGoogle Scholar
  • 14 Li D, Sedano S, Allen R, Gong J, Cho M, Sharma S. Current treatment landscape for advanced hepatocellular carcinoma: Patient outcomes and the impact on quality of life. Cancer s (Basel) 2019; 11: 11
    Google Scholar
  • 15 Nanda R, Liu MC, Yau C, Asare S, Hylton N, Veer LVT. et al Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): Results from I-SPY 2. J Clin Oncol 2017; 15 Suppl 35: 506
    CrossrefGoogle Scholar
  • 16 Loibl S, Untch M, Burchardi N, Huober JB, Blohmer JU, Grischke EM. et al. Randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC). J Clin Oncol 2018; 15 Suppl 36: 14
    Google Scholar
  • 17 Schmid P, Park Y, Muñoz-Couselo E, Kim S-B, Sohn J, Im SA. et al. Abstract PD5–01: KEYNOTE-173: Phase 1b multicohort study of pembrolizumab (Pembro) in combination with chemotherapy as neoadjuvant treatment for triple-negative breast cancer (TNBC). Cancer Res 2019; 4 Suppl 79: PD5-01
    Google Scholar
  • 8 Necchi A, Raggi D, Gallina A, Madison R, Colecchia M, Lucianò B. et al. Updated results of PURE-01 with preliminary activity of neoadjuvant pembrolizumab in patients with muscle-invasive bladder carcinoma with variant histologies. Eur Urol 2020; 77: 439-46
    CrossrefPubMedGoogle Scholar
  • 19 Abdel-Rahman O. Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: A systematic review. Immunotherapy 2016; 8: 1383-91
    CrossrefPubMedGoogle Scholar
  • 20 Marin-Acevedo JA, Chirila RM, Dronca RS. Immune checkpoint inhibitor toxicities. Mayo Clin Proc 2019; 94: 1321-9
    CrossrefPubMedGoogle Scholar
  • 21 Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F. et al. Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis. JAMA Oncol 2018; 4: 1721-8
    CrossrefPubMedGoogle Scholar
  • 22 Kennedy LB, Salama AK. A review of cancer immunotherapy toxicity. CA Cancer J Clin 2020; 70: 86-104
    CrossrefPubMedGoogle Scholar
  • 23 Trinh S, Le A, Gowani S, La-Beck NM. Management of immune-related adverse events associated with immune checkpoint inhibitor therapy: A minireview of current clinical guidelines. Asia Pac J Oncol Nurs 2019; 6: 154-60
    CrossrefPubMedGoogle Scholar
  • 24 FDA Accepts Merck's Supplemental Biologics License Applications for KEYTRUDA® (Pembrolizumab) Six-Week Dosing Schedule for Melanoma and Multiple Other Indications. Kenilworth, NJ: Merck; July 9, 2019. Available from: https://bit.ly/2xzRfnE. [Last accessed on 2019 Jul 09].