1. YOUR CANCER TREATMENT: WHAT TO EXPECT FROM THE LATEST ADVANCEMENTS MIRIAM J. ATKINS, M.D.

2. 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

3. 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

4. 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

5. HOW CHECKPOINT INHIBITORS WORK

6. CHECKPOINT INHIBITORS Specific indications Not used as first line treatment except Ipilimumab for Melanoma Well tolerated but can have serious side effects

7. 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

8. 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

9. 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

10. 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

11. CHECKPOINT INHIBITORS Very effective Well tolerated Different measurement of response Can have serious, late side effects

12. 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

13. RESPONSE TO IMMUNOTHERAPY (PSEUDOFLARE)

14. SIDE EFFECTS (-ITIS) Pneumonitis Colitis Hepatitis Nephritis Encephalitis Endocrinopathies (Diabetes, Hypothroid) Rash

15. PNEUMONITIS Radiograhpic changes New or worsening cough Chest pain Shortness of breath Treat with steroids

16. COLITIS Diarrhea Bloody stools Severe stomach or abdominal pain Treat with steroids or Infliximab, if severe

17. HEPATITIS Elevated liver function tests or bilirubin Jaundice Nausea and vomiting Right sided abdominal pain Treat with steroids

18. 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.

19. NEPHRITIS Increase creatinine Decrease urine output Swelling in ankles Loss of appetite Blood in urine Treat with steroids

20. SKIN TOXICITY Rash Itchy skin Blisters Mouth ulcers Treat with steroids

21. ENCEPHALITIS Headache, confusion, hallucinations Fever Tiredness or weakness, sleepiness Seizures Stiff neck Treat with steroids

22. 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

23. QUESTIONS??

24. THANK YOU