Immunotherapy - Memorial Hospital · July 2014 •87 year old with metastatic adenocarcinoma of the...
Transcript of Immunotherapy - Memorial Hospital · July 2014 •87 year old with metastatic adenocarcinoma of the...
ImmunotherapyEdward R. Arrowsmith MD, MPH
Tennessee Oncology
Disclosures:
I have no financial disclosures
Case Presentation
July 2014
• 87 year old with metastatic adenocarcinoma of the lung
• Previously treated with chemotherapy with poor tolerance
• Options• Additional cytotoxic chemotherapy
• Clinical trial
• Hospice care
• Enrolled on LUN 272• Treatment with BMS-936558 (Nivolumab)
ESMO 2017: 12970
Results
• Complete response
• Now 91 years old
• Remains free of disease
• Has never had side effects
Immune Checkpoint Inhibitors:Activity
Pembrolizumab vs. Chemotherapy for Bladder Cancer
NEJM 2017; 376:1025-1026
Stage III NSCLCDefinitive
Chemoradiation
Durvalumab for One Year
Placebo for One Year
NEJM 2017; 377:1919-1929
Checkpoint Inhibitors
Anti-PD1 or –PD-1L
• Nivolumab
• Pembrolizumab
• Avelumab
• Atezolizumab
• Durvalumab
• Cemipilimab*
Anti-CTLA4
• Nivolumab
• Tremilmumab*
*In Development
Check Point Inhibitos: Indications• Non-small cell lung cancer• Small cell lung cancer• Head & Neck cancer• Bladder cancer• Melanoma• Kidney cancer• Hodgkin lymphoma• Liver cancer• Microsatellite unstable solid tumors• Merkel cell carcinoma• Squamous cell carcinoma of the skin
Predictors of Response
• PDL-1 Staining on Tumor• Various methods
• Used clinically to select first line therapy for non-small cell lung cancer
• DNA Microsatellite Instability
• Tumor Mutational Burden• Counting number of genetic mutations in the tumor on genomic sequencing
• FDA has signaled willingness to approve therapies independent of tumor type based on this biomarker
Adverse Events
Side effects
• Most patients tolerate the infusions without side effects (we have done placebo controlled trials)
• Toxicities are autoimmune• Treatments are relatively contraindicated in RA, lupus, Crohn’s
Toxicities
• Toxicities• Rash
• Pneumonitis
• Colitis
• Hepatitis
• Endocrine abnormalities
• Therapy• Steroids (prednisone 1mg/kg or 2mg/kg)
• anti-TNF drugs
• Mycophenolate mofetil
Future Directions
• Combination Therapy
• Predictors of Response• Breast cancer
• Prostate cancer
• Colon cancer
• Pancreas cancer
• Earlier stages of disease• After surgery