Nivolumab Opdivo Study Materials

Nivolumab (Opdivo) MOA: PD-1 receptor inhibitor, immune checkpoint inhibitor Dosing 240 me with pilimumab 1 mg/ke on the same day every 3 weeks for a maximum of 4 doses, then 240 mg every 2 weeks or 480 mg every 4 weeks OR 240 mg every 2 weeks or 480 mg every 4 weeks Administration: In-line filter for administration Run over 30 minutes; always give first when giving in combo Monitoring: CBC w/diff and CMP prior to every dose Full thyroid panel (every 6 weeks.or every cycle if given with.ipi), Free random cortisol every 8 weeks No dose reduction for OPDIVO is recommended, in general, withhold OPDIVO for severe (Grade, 3) immune-mediated adverse reactions. Permanently discontinue OPDIVO for lifethreatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids ADRS: As a single agent: fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dysonea, constipation. decreased appetite, back pain, arthralgia, upper respiratory tract infection, pyrexia, headache, abdominal pain, vomiting, and urinary tract infection In combination with ipilimumab fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, constipation, decreased weight, and dizziness. Ipilimumab (Yervoy) MOA: CTLA4 inhibitor Dosing: 1 mg/kg on the same day every 3 weeks for a maximum of 4 doses ONLY in combo with Nivolumab. Not used as a single agent in CRC Administration: In-line filter for administration Run over 30 minutes Monitoring: CBC w/diff, CMP prior to every dose, full thyroid panel Free random cortisol every 6-9 weeks ADRS: Most common adverse reactions (≥20%) with YERVOY as a single agent are fatigue, diarrhea, pruritus, rash, nausea, and headache. (6.1) Most common adverse reactions (220%) with YERVOY in combination with nivolumab are fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, constipation, decreased weight, and dizziness < 27 35 EGFR TKI for NSCLC Treatment Drug Trade Name Dose Associated Facts Afatinib Gilotrif 40mg p.o. daily Highest incidence of diarrhea Erlotinib Tarceva 150mg p.o. daily Avoid use with PPIs/H2 blockers Gefitinib Iressa 250mg p.o. daily Avoid use with PPIs/H2 blockers Osimertinib* Tagrisso 80mg p.o. daily Confirm T790M EGFR mutation status in pre-treated Dacomitinib Vizimpro 45mg p.o. daily Severe & fatal diarrhea has occurred "All agents are considered first line by NCCN, but osimertintib is preferred The T790M EGFR mutation is associated with acquired resistance to EGFR TKI therapy This resistance occurs in approximately 60% of patients who initially respond to therapy Stage IV - M1 Disease First Line First line Therapy Combinations For Patients who CAN tolerate aggressive therapy FOLFIRINOX Addition of Bevacizumab FOLFOX Addition of Bevacizumab EFGR inhibitor ONLY FOR KRAS/NRAS/BRAF WT LEFT SIDED TUMORS FOLFIRI Addition of VEGF Inhibitor OR EGFR inhibitor EFGR inhibitor ONLY FOR KRAS/NRAS/BRAF WT LEFT SIDED TUMORS Nivolumab + Ipilimumab OR pembrolizumab (dMMR, MSI-H only) First line Therapy For Patients who CAN'T tolerate aggressive therapy SFU + Leucovorin +/- Bevacizumab Capecitabine +/- Bevacizumab EFGR inhibitor ONLY FOR KRAS/NRAS/BRAF WT LEFT SIDED TUMORS Nivolumab or Pembrolizumab (dMMR, MSI-H only) Trastuzumab + Pertuzumab or Lapatinib (HER2 + and RAS/BRAF WT) EGFR TKI for NSCLC Treatment Drug Trade Name Dose Associated Facts Afatinib Gilotrif 40mg p.o. daily Highest incidence of diarrhea Erlotinib Tarceva 150mg p.o. daily Avoid use with PPIs/H2 blockers Gefitinib Iressa 250mg p.o. daily Avoid use with PPIs/H2 blockers Osimertinib* Tagrisso 80mg p.o. daily Confirm T790M EGFR mutation status in pre-treated Dacomitinib Vizimpro 45mg p.o. daily Severe & fatal diarrhea has occurred "All agents are considered first line by NCCN, but osimertintib is preferred The T790M EGFR mutation is associated with acquired resistance to EGFR TKI therapy This resistance occurs in approximately 60% of patients who initially respond to therapy Summary of Antimetabolites Folate analogs/antagonists #Methotrexate and pemetrexed Purine analogs #6-mercaptopurine, 6-thioguanine (S in the nucleobase) *Fludarabine, clofarabine (fluorine in the nucleobase; presence of deoxyribose) Pyrimidine analogs 5-FU (F in nucleobase); floxuridine (5-FU w/deoxyribose); capecitabine (prodrug of 5-FU; contains deoxyribose) Cytarabine (cytosine with deoxyribose); gemcitabine (fluoridated deoxyribose) #azacytidine (cytidine with additional N) All active in S-phase of cell cycle Main toxicities - myelosuppression, Gl tox and hyperuricemia (most) PO activity - MTX, 6-MP, 6-TG, Capecitabine Can give IT-MTX, cytarabine 32 Systemic therapy Immunotherapy *Anti-PD-1 pembrolizumab (Keytruda) OR nivolumab (Opdivo) *Nivolumab + ipilimumab (Yervoy) Targeted therapy *B-RAF V600E mutation - Vemurafenib (Zelboraf), dabrafenib (Tafinlar) and encorafenib (Braftovi) MEK inhibitor - trametinib (Mekinist), cobimetinib (Cotellic) and binimetinib (Mektovi) Other regimens *Cytotoxic regimens - Dacrabazine Temozolomide } Alkylating Agents - Triazenes Paclitaxel (or Abraxane) -Carboplatin/paclitaxel *Bio-chemotherapy Dacarbazine or temozolamide and a platinum vinblastin/nitrosurea and IL-2 +