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 T- cells 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 platinum- containing 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

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