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

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://www.nature.com/nrclinonc/journal/v11/n1/fig_tab/nrclinonc.2013.208_F2.html&ei=uH65VLWWFceLNqWigqAF&bvm=bv.83829542,d.eXY&psig=AFQjCNEGc55qpq_ttgv-gyCLOzGmyNI36w&ust=1421529123610560

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