The Myfanwy Townsend Melanoma Research Fund

Tackling Rising Rates of Melanoma

Dr James Larkin: Working on Advanced Melanoma

Dr James Larkin is a Consultant Medical Oncologist at The Royal Marsden specialising in the treatment of advanced melanoma, the most aggressive form of skin cancer.

Over the past few years Dr Larkin and his team have been responsible for some of the biggest breakthroughs in the treatment of the disease seen in the past three decades.

Ipilimumab

Dr Larkin was also involved with the trials which demonstrated that the immunotherapy agent ipilimuab improves the survival of patients and in some patients the impact is long term. It was the first drug that harnesses the power of the immune system to demonstrate a survival benefit effect in randomised trials.

The results of the trial revealed that the drug improved overall survival in previously untreated patients with advanced melanoma. In an earlier Phase III trial almost double the number of patients (46%) were still alive at one year and similar proportions were observed at two years with 24% still living.

Vemurafenib

In 2011 A Phase II study led in the UK by Dr Larkin and his team at The Royal Marsden heralded the biggest breakthrough in the treatment of advanced melanoma for over 30 years. Results showed that the pill vemurafenib extends overall survival in advanced melanoma patients compared to standard dacarbazine chemotherapy. Around half of patients with the disease have the BRAF genetic mutation, which drives the cancer cells to grow and spread. The new pill targets and blocks the mutated BRAF protein, causing tumours to shrink.

Combined Melanoma Drug Trial

Led by Dr Larkin, The Royal Marsden is currently pioneering the clinical trial of a new drug combination for the treatment of advanced melanoma. The Phase III trial is testing a new drug, nivolumab, in combination with another drug, ipilimuab which is a standard treatment option for advanced melanoma.

Both these drugs are types of immunotherapy, a treatment designed to boost the body’s natural defences to fight the cancer. Nivolumab is an anti-PD-1 immunotherpy which means it helps restore the natural ability of the immune system to recognise and target cancer.

An earlier study suggested that pairing the two drugs works better to shrink the advanced melanoma and has a high response rate. In preliminary results for this combination of drugs, three out of six patients who received the highest dose of nivolumab showed tumour shrinkage and the drugs also worked quickly with three out of four patients having tumour shrinkage within three months of starting treatment.

Investigational anti-PD-1 immunotherapy, MK-3475

The ongoing MK-3475, an investigational anti-PD-1 immunotherapy (like nivolumab), trial recently announced that patients with advanced melanoma showed an estimated overall survival rate of 81% at one year. This is the first time overall survival data has been presented from the 135 patients on the trial.

Many tumours are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK- 3475 is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.

 

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