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Dr Brian Bird Blogs from ASCO Annual Meeting 2015

Monday 09 November 2015

Dr. Brian Healey Bird BA MB BCh BAO FRCPI Is a Consultant Medical Oncologist, with the Bon Secours Cork, a Senior Clinical Investigator, with our Cancer Research Centre and a Senior Clinical Lecturer & Lecturer in Clinical Education, University College Cork.

Areas of expertise include:
- Lymphoma
- GI Cancer - colon, oesophagus, stomach, small bowel
- Melanoma
- Lung Cancer
- Breast Cancer
- Cancer Survivorship
- Clinical Trials

 

Dr. Healey Bird attended the recent American Society of Clinical Oncology general meeting in Chicago. Here he blogs about his findings at the event:

Is immunotherapy the “common denominator” that we can use to treat many different cancers?

The answer is “yes but”. We will be able to help many more patients than EVER before. I feel great excitement for my current and future patients with lung cancer and melanoma. In one trial combining two immunotherapy drugs (ipilumumab and nivolumab)  reported at ASCO 2015 58% of patients with Stage IV melanoma saw their tumours shrink.http://meetinglibrary.asco.org/content/144621-156

In another trial squamous non small cell lung cancer patients whose tumours had progressed on first line chemotherapy did substantially better and had fewer side effects with immunotherapy (nivolumab)  than when treated with second line chemotherapy (docetaxel).  At one year 42% of the immunotherapy patinets were alive compared with 24% of the patients who received chemotherapy.

http://meetinglibrary.asco.org/content/144815-156

However most patients’ tumours still progress, even when treated with combinations of very expensive drugs. How can we help the patients whose tumours still scoff at our new weapons? Can any society afford to pay 1 million dollars per year for one patient’s drug costs alone? As I sat with thousands of other oncologists in huge halls in Chicago I was excited to be part of the team at CCRC who strives to answer these questions. I remembered Professor Gerry O’Sullivan, who founded CCRC and his belief that the immune system held the key to fighting cancer.

At this year’s ASCO all the excitement was focused on immune checkpoint inhibitors (ICH) or drugs which “take the brakes off” the immune system. We have an immune system that usually  does a great job fighting viruses and bacteria. It also attacks cells that have mutated and might give rise to cancer. By the time we know a patient has cancer the immune system has failed. It either cannot “see” the cancer or cannot “attack” it. Cancer cells protect themselves by displaying a surface protein called Programmed Death Ligand. This binds to Programmed Death Ligand receptors on the surface of attacking immune T cells and turns them off.  There are a number of artificial antibodies which interfere with this negative signal from the tumour to the T cell (drugs such as nivolumab and pembrolizumab). The activated T cells then punch holes in the tumour cells killing them. In patients who don’t have enough T cells already trying to attack the tumour, blocking another checkpoint called CTLA4 enables the immune system to detect the tumour and produce T cells designed to attack it. When these drugs are combined we see extra efficacy and amazing results. Patients are living longer with fewer side effects.

Normally immune checkpoints stop the immune system attacking healthy cells in our bodies which would cause autoimmune disease like arthritis or colitis. So these “wonder drugs” which unleash the immune system have side effects completely different to conventional chemotherapy which damages cancer cells directly. Patients’ immune systems may attack healthy lung, gut or skin cells. Usually steroids suffice to dampen down the misdirected attack but sometimes stronger drugs which rheumatologists and gastroenterologists use in autoimmune disease are required. There will be a learning curve in oncology as we gain more experience.

The keynote address at ASCO was given by Dr Suzanne L. Topalian from Johns Hopkins whose life work in immunotherapy was recognised with the Karnofsky Award. She spoke about challenges facing the field – helping the immune system to recognise cancer cells and trying to determine which patients need which drugs. One way to stimulate the immune system is by damaging a single site of the tumour. As the cells die slowly they stimulate the immune system to attack them and to learn how to attack tumour cells elsewhere in the body. CCRC has pioneered the use of electrochemotherapy in Ireland with fantastic results for single tumor lesions. CCRC scientists have increased the efficacy of immunotherapy with electrochemotherapy. This will soon be brought into clinical trials by my colleague Dr Derek Power CUH and others. So one “but” – the fact that many patients don’t respond may soon be overcome.

The second “but” – we don’t have a good test to say which patient needs which drug, one checkpoint inhibitor or two. At the moment we can stain for how much PDL1 a tumour has prior to treatment. Roughly speaking the more PDL1 the more likely a drug targeting this pathway will work. Drugs targeting CTLA4 may increase PDL1 expression and make anti PDL1 therapy successful. So patients with a lot of PDL1 on their tumour just need nivolumab but those with low PDL1 levels need nivolumab and an anti CTLA4 drug such as ipilumumab. CCRC is working to develop biomarkers or tests of patients’ blood and tissue which can more accurately predict whether the immune system is attacking the cancer and being thwarted by PDL1. Accurate biomarkers will enable doctors like me to select these expensive drugs only for those most likely to benefit.

So I return from ASCO with my passion for patient focussed research refreshed and happy to be a small part of answering some big questions.

 

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