Personalised Medicine in Melanoma
Understanding of molecular biology, progress in research of biomarkers, diagnostics and clinical benefit from the latest treatment advances
We met with Reinhard Dummer, a Vice-chairman of the Department of Dermatology in the Cancer Unit at University Hospital in Zurich, Switzerland to discuss on how deeper understanding of molecular biology is relevant for treatment decision in patients with diverse group of melanomas, progress in research of biomarkers, diagnostics and clinical benefit observed from the latest treatment advances.
ESMO: How is the molecular biology of melanoma specific to that cancer?
Reinhard Dummer: Melanoma is a tumour entity that has a very high frequency of mutations, especially UV induced mutations. Some mutations are shared with other cancer types, others are not. Actually we should not talk about melanoma, but we should talk about the melanomas. Because there are many subtypes of melanoma and today we are starting to define them based on their mutation pattern. For example, there is B-RAF mutated melanoma, there’s NRAS mutated melanoma, there’s C-KIT mutated melanoma... We still continue to find new subtypes regularly, so there are subtypes that are characterised by NF1 changes, and very recently the USA research groups have described translocations that lead to the activation of oncogenes such as B-RAF or others. It is very interesting because they can be targeted by medications that are already available or in use for other cancer types.
ESMO: How does the understanding of molecular biology impact the way patients with melanoma are treated?
Reinhard Dummer: Today, we do at least three different tests for mutations, we already did some tests for protein expression and we also investigate tumour suppressors such as p53. This information put together gives us an avenue that we can follow for the treatment of the individual.
ESMO: What is the impact of personalised medicine on the treatment of patients with melanoma?
Reinhard Dummer: In my opinion, melanoma is a paradigm for personalised medicine or precision medicine. It's really ahead of many other malignancies. So, for me, in a patient with stage four of the disease it is essential to have a list of mutations checked and maybe in the very near future we will also check for translocation. But there is also another level that is relevant, the protein level. For example I want to know if the patient expresses cancer testis antigene that can be used for a vaccination or to know about the immune status? There are molecules such as PD1 ligand that predict the outcome of immunotherapy.
ESMO: How important is research into biomarkers?
Reinhard Dummer: Biomarkers are the basis for precision medicine. Without biomarkers, precision medicine will not become reality, so we have to invest in finding new biomarkers. But finding them is just one side, you have to know what is the exact value of this biomarker and when we can use this marker. The duration to validate the biomarker depends on what it's used for. The most relevant biomarkers are biomarkers that have an impact on survival, can predict survival time, and identify high-risk groups but their validation can take a very long time.
ESMO: How does the future look in terms of the treatment of melanomas?
Reinhard Dummer: The future for melanoma therapy in my opinion looks really bright. We have many new options, actually in my daily practice I avoid chemotherapy in many patients. We use targeted therapy and we use immunotherapy. We have successful examples for both treatment options now and the next molecules are already in the pipeline. We have combined B-RAF inhibitors and MEK inhibitors and could show that these two molecules increase the progression-free survival without having more toxicity and a similar situation is observed with ipilimumab and anti-PD1 antibodies. We have proven evidence that ipilimumab has a long-term benefit for our patients and now we can add on additional strategies. And if we manage to bring targeted therapy and immunotherapy together, I think this will really result in a much better prognosis for our patients.
ESMO: What do patients need to know about the personalisation of treatment of melanoma?
Reinhard Dummer: My advice would be - the treatment of melanoma is really developing rapidly, so if you suffer from diseases or somebody from your family, please visit an expert. There are really many new treatment options and specialised melanoma centres will help you to find the best individual approach for your disease. I feel really very optimistic for the future of melanoma treatment now and I can tell you this was not the case for the last fifteen years when I was very frustrated. We have treated more than three thousand patients in clinical trials without any signs of benefit. But now finally I think we have good times in front of us with many perspectives. But the final goal for us is to cure melanoma.
ESMO: Are the patients already benefiting from these advances or is this something that will take several years to observe benefit?
Reinhard Dummer: In my department, we are carefully monitoring the survival times of patients treated also outside the clinical trials and we can see a significant improvement over the last three years.