Immunotherapy to Address Unmet Needs in Oncology; Two Clinical Vignettes of Response in Metastatic Malignant Melanoma and Non-Small Cell Lung Cancer

Document Type : Case Study

Authors

1 NK Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon

2 Department of Neuroscience, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences

3 Behphar Scientific Committee, Behphar Group, Tehran

Abstract

The management of unresectable advanced, metastatic malignant melanoma (MM) and chemotherapy-resistant or refractory non-small cell lung cancer (NSCLC) has been an uphill challenge in clinical oncology. The advent of immunotherapy in cancer has put forward some new hopes to cover unmet needs in treating such cases. Immune-checkpoint inhibitors are among the well-supported options in the same vein.  Alongside other cancer immunotherapy class-molecules, pembrolizumab (PZB), a programmed cell death protein 1 (PD-1) blocking antibody, has recently been approved both for MM and NSCLC. This report presents an overview of the clinical benefits of PZB in MM and NSCLC and highlights the clinical features of two eligible cases who have undergone immunotherapy using PZB. 

Keywords


  1. Hutchinson L. Immunotherapy: pembrolizumab-is the writing on the wall for cancer? Nature reviews Clinical oncology. 2015;12(7):371.
  2. Guilleminault L, Carmier D, Heuze-Vourc'h N, Diot P, Pichon E. [Immunotherapy in non-small cell lung cancer: inhibition of PD1/PDL1 pathway]. Revue de pneumologie clinique. 2015;71(1):44-56.
  3. Flemming A. Cancer: PD1 makes waves in anticancer immunotherapy. Nature reviews Drug discovery. 2012;11(8):601.
  4. Kline J, Gajewski TF. Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. Current opinion in investigational drugs. 2010;11(12):1354-9.
  5. Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. The New England journal of medicine. 2015;372(26):2521-32.
  6. Pembrolizumab FDA approval. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125514lbl.pdf.
  7. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. The New England journal of medicine. 2015;372(21):2018-28.
  8. Mony JT, Zhang L, Ma T, Grabosch S, Tirodkar TS, Brozick J, et al. Anti-PD-L1 prolongs survival and triggers T cell but not humoral anti-tumor immune responses in a human MUC1-expressing preclinical ovarian cancer model. Cancer immunology, immunotherapy : CII. 2015;64(9):1095-108.
  9. Chang HN, Liu BY, Qi YK, Zhou Y, Chen YP, Pan KM, et al. Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy. Angewandte Chemie. 2015;54(40):11760-4.
  10. Blake SJ, Ching AL, Kenna TJ, Galea R, Large J, Yagita H, et al. Blockade of PD-1/PD-L1 promotes adoptive T-cell immunotherapy in a tolerogenic environment. PloS one. 2015;10(3):e0119483.
  11. Patel SP, Kurzrock R. PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Molecular cancer therapeutics. 2015;14(4):847-56.
  12. Errico A. Immunotherapy: PD-1-PD-L1 axis: efficient checkpoint blockade against cancer. Nature reviews Clinical oncology. 2015;12(2):63.
  13. Muenst S, Soysal SD, Tzankov A, Hoeller S. The PD-1/PD-L1 pathway: biological background and clinical relevance of an emerging treatment target in immunotherapy. Expert opinion on therapeutic targets. 2015;19(2):201-11.
  14. Aarts MJ, van den Borne BE, Biesma B, Kloover JS, Aerts JG, Lemmens VE. Improvement in population-based survival of stage IV NSCLC due to increased use of chemotherapy. International journal of cancer Journal international du cancer. 2015;136(5):E387-95.
  15. Carter D. New drug for metastatic melanoma increases survival rate. The American journal of nursing. 2011;111(9):16.
  16. Keytruda PI. Available from: https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf.
  17. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948):1109-17.
  18. Clinical Trials Registry Pembrolizumab. Available from: https://www.clinicaltrialsregister.eu/ctr-search/search?query=MK-3475.
  19. Clinicaltrials.gov Registry_Pembrolizumab. Available from: https://www.clinicaltrials.gov/ct2/results?term=pembrolizumab.
  20. Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Calio A, et al. Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers. PloS one. 2015;10(6):e0130142.
  21. Barbee MS, Ogunniyi A, Horvat TZ, Dang TO. Current status and future directions of the immune checkpoint inhibitors ipilimumab, pembrolizumab, and nivolumab in oncology. The Annals of pharmacotherapy. 2015;49(8):907-37.