Immune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatm

Table 3. Combination of immunotherapy and radiotherapy IMMUNOTHERAPY PHASE 0 PHASE I Pembrolizumab/MK-3475/ Keytruda (anti-PD-1) Previously untreated esophageal cancer NCT02463994 Atezolizumab/MPDL3280A (anti-PD-L1) NSCLC NCT02587455 Pembrolizumab/MK-3475/ Keytruda Thoracic tumors NCT02608385 NSCLC, previously treated with standard of care NCT02303366 Oligometastatic breast cancer NCT02402920 SCLC NCT02560636 Invasive bladder cancer NCT02298946 PHASE I/II PHASE II OTHER THERAPIES Chemotherapy AMP-224 (anti-PD-1) Colorectal cancer Chemotherapy NCT02383212 REGN281 (anti-PD-1) Advanced malignancies Chemotherapy NCT02400814 Atezolizumab/MPDL3280A Recurrent or stage IV NSCLC NCT02407171 Pembrolizumab/MK-3475/ Keytruda Melanoma, lung cancer NCT02584829 Avelumab (anti-PD-L1) Metastatic Merkel cell carcinoma Recombinant IFN-beta or MCPyV Tag-specific polyclonal autologous CD-8+ T cells NCT02586610 Pembrolizumab/MK-3475/ Keytruda Rectal cancer Chemotherapy NCT02599779 Stage IV TKI-refractory renal cell cancer NCT02289209 Inoperable recurrence or second primary squamous cell carcinoma of the head and neck NCT02677155 Follicular lymphoma Rituximab, autologous dendritic cells, and GM-CSF NCT02648282 Pancreatic cancer Chemotherapy and GVAX (pancreatic cancer vaccine) TNBC Chemotherapy NCT02499367 Nivolumab/Opdivo (anti-PD-1) Old Stars: Cytokines Cytokines have been part of the immuno-oncology arsenal for years, with interferon (IFN) first approved in 1986 for cancer treatment and has subsequently been approved and used via subcutaneous or intramuscular injections for hairy cell leukemia, malignant melanoma, non-Hodgkin lymphoma, AIDS-related Kaposi sarcoma, hepatitis C infection, and hepatitis B infection.17 The interleukin (IL) family also has a role in immune signaling, and IL-2, which regulates the immune system and acts as a growth factor that stimulates proliferation and differentiation of many immune cells, is an FDA-approved immunotherapy option for melanoma and kidney cancer and was initially approved in 1992. 8 CONDITION NCT02642809 IL-2 in particular has proven effective in metastatic melanomas and metastatic renal cell carcinoma, with a recent study reporting an overall survival at 2 years of 60.6% in 91 patients.18 However, severe toxic effects are common because of the systemic stimulation of profound lymphocytosis, eosinophilia, and thrombocytopenia2 and include pulmonary edema, capillary leak syndrome, hypotension, impaired liver function, fever, and chills. For this reason, when administered at high doses, a hospital stay is required during treatment. Furthermore, the overall cure rate is only 6%.16 However, just like Harrison Ford, who returned to help potentiate the Star Wars series in the most recent installation, some of the older immuno-oncology agents might help to further research of the newer stars. The

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