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YOUR CANCER TREATMENT: WHAT TO EXPECT FROM THE LATEST ADVANCEMENTS MIRIAM J. ATKINS, M.D. IMMUNOTHERAPY • Vaccines – stimulate the immune system against tumor antigens (Sipucel-T) • Cytokines – stimulate broad based immune response (interferon alpha) • Oncolytic Virus Therapy – genetically modified viruses to kill cancer cells (T-VEC) • Monoclonal Antibodies – therapy designed to attach to specific proteins in a cancer cell IMMUNE SYSTEM TERMINOLOGY • T-cells – patrol the body searching for signs of disease or infection • B-cells – bind to specific antigens and initiate an antibody response • Cytotoxic T-lymphocyte Associated Protein 4 (CTLA-4) – located on the surface of Tcells in certain cancers • Programmed Death 1 (PD-1) – inhibitory receptor expressed by T-cells ln certain tumors • Programmed Death Ligand 1 (PDL-1) – maintain immune homeostasis. Bind to receptors on T-cells WHAT ARE CHECKPOINT INHIBITORS • Drugs, often made of antibodies • Block normal proteins on cancer cells • Block proteins on T cells that respond to cancer cells • Seek to overcome one of cancer’s main defenses of immune system attack HOW CHECKPOINT INHIBITORS WORK CHECKPOINT INHIBITORS • Specific indications • Not used as first line treatment except Ipilimumab for Melanoma • Well tolerated but can have serious side effects NEW AGENTS (CHECKPOINT INHIBITORS) • Pembrolizumab (Keytruda) – PD-1 blocking antibody (inhibitor) approved for treatment of Melanoma and Non-small cell lung cancer • Nivolumab (Opdivo) – PD-1 inhibitor approved for treatment of Non-small cell lung cancer, Melanoma, and Renal Cell Carcinoma • Ipilimumab (Yervoy) – antibody against CTLA-4 approved for treatment of Melanoma PEMBROLIZUMAB • Non-small cell lung cancer that expresses PDL-1 with disease progression after platinumcontaining chemotherapy regimen • After treatment with agents for cancers with EGFR or ALK genomic tumor aberrations NIVOLUMAB • Metastatic Non-small cell Lung cancer with progression after platinum-based chemotherapy • Metastatic non-small cell lung cancer after therapy with EGFR and ALK inhibiting agents, if the patient has these genomic aberrations • Metastatic or unresectable Melanoma in combination with Ipilimumab in patients with BRAF wild-type • Advanced Renal Cell Carcinoma who have received anti-angiogenic therapy IPILIMUMAB • Monoclonal antibody that stimulates the immune system by targeting CTLA-4 • Cytotoxic T Lymphocytes (CTLs) recognize and destroy cancer cells • Turns off the inhibitory mechanism and allows the CTLs to function • Approved for the treatment of melanoma CHECKPOINT INHIBITORS • Very effective • Well tolerated • Different measurement of response • Can have serious, late side effects TUMOR RESPONSE TO IMMUNOTHERAPY • Depends on how well your immune system can target the cancer cells • Immunotherapy my help shrink the tumor • Slow the growth of the tumor • Stop the active growth of the tumor • The tumor may look larger on the initial scans RESPONSE TO IMMUNOTHERAPY (PSEUDOFLARE) SIDE EFFECTS (-ITIS) • Pneumonitis • Colitis • Hepatitis • Nephritis • Encephalitis • Endocrinopathies (Diabetes, Hypothroid) • Rash PNEUMONITIS • Radiograhpic changes • New or worsening cough • Chest pain • Shortness of breath • Treat with steroids COLITIS • Diarrhea • Bloody stools • Severe stomach or abdominal pain • Treat with steroids or Infliximab, if severe HEPATITIS • Elevated liver function tests or bilirubin • Jaundice • Nausea and vomiting • Right sided abdominal pain • Treat with steroids ENDOCRINOPATHIES • Hypo/hyperthyroidism • Diabetes • Adrenal insufficiency • Headaches, extreme fatigue, weight gain or loss, dizziness, mood changes hair loss increased thirst or urination • Treat with steroids, insulin, thyroid hormone replacement, etc. NEPHRITIS • Increase creatinine • Decrease urine output • Swelling in ankles • Loss of appetite • Blood in urine • Treat with steroids SKIN TOXICITY • Rash • Itchy skin • Blisters • Mouth ulcers • Treat with steroids ENCEPHALITIS • Headache, confusion, hallucinations • Fever • Tiredness or weakness, sleepiness • Seizures • Stiff neck • Treat with steroids CONCLUSIONS • Check point inhibitors are part of the future of cancer treatment • Using the immune system to fight cancer is a novel concept • Ongoing clinical trials with many tumor types • Well tolerated but, can have serious late side effects • Do not hesitate to contact your physician if you are being treated with these medications and have what appears to be minor side effects QUESTIONS?? THANK YOU
