In the last ten years, immune control point inhibitors (ICPI 'S) have been one of the most significant breakthroughs in cancer therapy. Different studies have reported desired clinical activity and durable response amongst advanced non-small cell lung cancer(NSCLC) patients in programmed cell death protein 1 ( Pd-1) and programmed death ligand 1 (PD-L1). Such findings have led to changes in the current advanced NSCLC therapy methods, and a new standard first-line treatment option has been introduced for patients with PD-L1 positives. In October 2016, the United States Food and Drug Administration (US FDA ) approved Pembrolizumab, a highly selective, humanised antipD-1 monoclonal antibody. Platinum-based chemotherapy is the first line treatment for advanced non-small cell lung cancer (NSCLC). Pembrolizumab replaced cytotoxic chemotherapy as the first line of treatment of choice in all patients with a tumour ratio score of 50% or higher for programmed death ligand 1 (PD-L1). Pembrolizumab was significantly higher in chemotherapy than chemotherapy with desirable responses and progressions free survival.

Keywords: Pembrolizumab, NSCLC, PD-L1, ICPI, Keytruda, Tumour Proportion Score.

1. Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015). Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer cell, 27(4), 450-461.
2. Mahoney, K. M., Rennert, P. D., & Freeman, G. J. (2015). Combination cancer immunotherapy and new immunomodulatory targets. Nature reviews Drug discovery, 14(8), 561-584.
3. Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A (December 2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet Oncology. 18 (12)
4. Francisco LM, Sage PT, Sharpe AH (July 2010). "The PD-1 pathway in tolerance and autoimmunity". Immunological Reviews. 236: 219–42.
5. Fife BT, Pauken KE (January 2011). "The role of the PD-1 pathway in autoimmunity and peripheral tolerance". Annals of the New York Academy of Sciences. 1217: 45–59.
6. Butte MJ, Peña-Cruz V, Kim MJ, Freeman GJ, Sharpe AH (August 2008). "Interaction of human PD-L1 and B7-1". Molecular Immunology. 45 (13): 3567–72.
7. Said EA, Dupuy FP, Trautmann L, Zhang Y, Shi Y, El-Far M, Hill BJ, Noto A, Ancuta P, Peretz Y, Fonseca SG, Van Grevenynghe J, Boulassel MR, Bruneau J, Shoukry NH, Routy JP, Douek DC, Haddad EK, Sekaly RP (April 2010). "Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection". Nature Medicine. 16 (4): 452–9.
8. Michaelidou, K., Agelaki, S., & Mavridis, K. (2020). Molecular markers related to immunosurveillance as predictive and monitoring tools in non-small cell lung cancer: recent accomplishments and future promises. Expert Review of Molecular Diagnostics, 20(3), 335-344.
9. FDA approves pembrolizumab for advanced esophageal squamous cell cancer". U.S. Food and Drug Administration (FDA) (Press release). 30 July 2019. Retrieved 10 January 2020.
10. Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A (2017). "De-novo and acquired resistance to immune checkpoint targeting". The Lancet Oncology. 18 (12)
11. Keytruda- pembrolizumab injection, powder, lyophilized, for solution Keytruda- pembrolizumab injection, solution". DailyMed. 17 September 2019. Retrieved 10 January 2020.
12. Keytruda 50 mg powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC)". (emc). 25 November 2019. Retrieved 10 January 2020.
13. Buqué A, Bloy N, Aranda F, Castoldi F, Eggermont A, Cremer I, Fridman WH, Fucikova J, Galon J, Marabelle A, Spisek R, Tartour E, Zitvogel L, Kroemer G, Galluzzi L (July 2010). "The PD-1 pathway in tolerance and autoimmunity". Immunological Reviews. 236: 219–42
14. Buqué, Aitziber (April 2015). "Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications".
15. Pardoll DM (March 2012). "The blockade of immune checkpoints in cancer immunotherapy". Nature Reviews Cancer. 12 (4): 252–64.
16. Bala S, Nair A, Lemery S, et al. (30 May 2017). "FDA D.I.S.C.O.: First Tissue/Site Agnostic Approval Transcript". U.S. Food and Drug Administration (FDA).
17. https://www.cancer.gov/news-events/cancer-currents-blog/2015/pembrolizumab-nsclc
18. Linardou, Helena; Gogas, Helen (July 2016). "Toxicity management of immunotherapy for patients with metastatic melanoma". Annals of Translational Medicine. 4 (14): 272
19. Wang, S., Zimmermann, S., Parikh, K., Mansfield, A. S., & Adjei, A. A. (2019, August). Current diagnosis and management of small-cell lung cancer. In Mayo Clinic Proceedings (Vol. 94, No. 8, pp. 1599-1622). Elsevier.
20. Pai‐Scherf, L., Blumenthal, G. M., Li, H., Subramaniam, S., Mishra‐Kalyani, P. S., He, K., ... & McKee, A. E. (2017). FDA approval summary: pembrolizumab for treatment of metastatic non‐small cell lung cancer: first‐line therapy and beyond. The oncologist, 22(11), 1392.
21. Lim, S. H., Sun, J. M., Lee, S. H., Ahn, J. S., Park, K., & Ahn, M. J. (2016). Pembrolizumab for the treatment of non-small cell lung cancer. Expert opinion on biological therapy, 16(3), 397-406.
22. Dang, T. O., Ogunniyi, A., Barbee, M. S., & Drilon, A. (2016). Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. Expert review of anticancer therapy, 16(1), 13-20.
23. Malhotra, J., Jabbour, S. K., & Aisner, J. (2017). Current state of immunotherapy for non-small cell lung cancer. Translational lung cancer research, 6(2), 196.
24. Postow, M. A., Callahan, M. K., & Wolchok, J. D. (2015). Immune checkpoint blockade in cancer therapy. Journal of clinical oncology, 33 (17), 1974.
25. Qin, Q., & Li, B. (2019). Pembrolizumab for the treatment of nonsmall cell lung cancer: Current status and future directions. Journal of cancer research and therapeutics, 15(4), 743.
26. Rihawi, K., Gelsomino, F., Sperandi, F., Melotti, B., Fiorentino, M., Casolari, L., & Ardizzoni, A. (2017). Pembrolizumab in the treatment of metastatic non-small cell lung cancer: a review of current evidence. Therapeutic advances in respiratory disease, 11(9), 353-373.
27. 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 randomised controlled trial. Lancet 387(10027), 1540–1550 (2016). Crossref, Medline, CAS, Google Scholar
28. 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. 375(19), 1823–1833 (2016). Crossref, Medline, CAS, Google Scholar
29. Fvasconcellos (talk • contribs) – From PDB entry 5DK3. More information: Scapin G, Yang X, Prosise WW, et al. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab. Nat Struct Mol Biol 2015; 22(12):953-8.

Kallem Sharat Venkat Reddy

Pharm-D, Bharat Institute of Technology

Address: H-no.1-76, Shantinagar, Vanasthalipuram

Hyderabad, Telangana-500070, India