The first sign Maureen had that something might be wrong was a cough that lingered long after the fall allergy season had come and gone. After having an x-ray, she was told that she needed to visit a pulmonary specialist, who after additional testing gave her the news that she had lung cancer. She was then referred to an oncologist who confirmed the diagnosis as stage IV and told her that she had 12-18 months to live, at most.
At the age of 55 Maureen was not ready to accept this as the truth. She knew there had to be other options out there, and sought the advice of a friend who gave her Dr. Scott Gettinger’s name at Smilow Cancer Hospital at Yale-New Haven. Dr. Gettinger is an Associate Professor of Medical Oncology and an expert in the treatment of lung cancers.
Maureen commented that from the moment she contacted Dr. Gettinger’s office she knew she wasn’t alone, “I was told that a whole team would be taking care of me including nurses, social workers, and physicians. This was wonderful news to hear and gave me the hope I needed to fight this disease. When I met with Dr. Gettinger he told me I was not curable, but treatable. I was relatively young and in good shape. This was not exactly a happy moment for me, but it gave me reassurance that there was something I could do to prolong my life.”
After hearing all of her options, Maureen decided on an aggressive course of chemotherapy. She showed progress, but could no longer tolerate the treatment. She received subsequent standard chemotherapy infusions, including an oral chemotherapy, and when these treatments failed, she entered her first clinical trial. While on this trial, she showed decrease in tumor growth in some areas, but also increase in others. Due to these increases, she was offered the choice between two new clinical trials. After weighing her options carefully and reviewing all the information with her doctor, she chose a trial testing the efficacy of a drug known as an anti-PD1 therapy.
The principle of anti-PD1 therapy was discovered in Dr. Lieping Chen’s laboratory. Dr. Chen is currently Professor of Immunobiology and Medicine, and Co-Director of the Cancer Immunology Program at Yale Cancer Center. Over 10 years ago he noticed that when he cultured T lymphocytes together with human cancer cells, these lymphocytes stopped attacking the cancer and shut down their activity. His laboratory went on to discover a protein called B7-H1 on human cancer cells that is responsible for the instruction of the lymphocytes to paralysis via a lymphocyte molecule called Programmed Death 1 (PD-1). His laboratory also found that the antibody that prevents the binding interaction of B7-H1 and PD-1 would allow the lymphocyte to do its job in fighting the cancer in mouse cancer models, which is now the basis for anti-PD-1 therapy.
Dr. Chen commented, “A group of specialized proteins on the immune cell surface bind to each other and communicate through biochemical signals that either push the cells into action or suppress their activity to fine tune immune responses to intruders such as viruses and bacteria. With cancer, the communications have been set in a wrong mode. But if you block this miscommunication, you can save the T lymphocyte to do the right thing and fight the cancer.”
For Maureen, this discovery was a miracle. A trial of anti-PD-1 therapy was initiated in five cancers: melanoma, kidney, prostate, colon, and lung. Maureen has been on the trial since June of 2010 and has shown a dramatic response to the therapy. At the time she entered the trial her prognosis was poor and her quality of life low. She had multiple areas of metastatic disease involving her liver, kidneys, lungs and heart. Over a year later all areas of disease have shown a substantial reduction with no re-growth.
“This drug is incredibly meaningful to patients like Maureen,” Dr. Gettinger said. “Unlike chemotherapy which is often tolerated poorly, this drug has been associated with few side effects. Maureen’s response has been extraordinary. She is living a normal life now, has fun, and enjoys working in her garden; this drug has given her, and other patients like her, their lives back.”
Now the goal is to determine why this drug is working in patients like Maureen, and not in others. The Yale clinics and labs have joined forces and by collecting blood samples and tumor tissue from patients; they hope to be able to discern which patients should be treated using this anti-tumor drug, and develop new therapies for those it’s not working for. “I am excited about this drug for many reasons, but the main reasons are because it is well tolerated by patients, the activity of the drug is remarkable and the results seem to be long-lasting,” said Dr. Gettinger.
“In a lot of ways this disease is more difficult emotionally than physically,” said Maureen. “You live six to eight weeks between CT scan results and hope for the best. My disease is the last thought I have before sleep and my first thought in the morning, and I am blessed every day that I get to take this medicine. I just celebrated 38 years of marriage to my wonderful husband, saw my youngest daughter graduate from college, my oldest daughter get married, and the birth of twin grandsons. None of that would have been possible without the support of my Smilow family and the opportunity to be on this trial. For that I will always be grateful.”