Advances in the treatment of lung cancer and melanoma

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Published: 17 Oct 2011
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Dr Raffaele Califano - The Christie NHS Foundation Trust, Manchester, UK

Dr Raffaele Califano talks to ecancer.tv about some of the latest advances in the treatment of lung cancer and melanoma. The main focus of this research is to effectively select the patients who will benefit most for each drug, allowing clinicians to maximise drug effectiveness and reduce the unnecessary adverse effects. To achieve this in lung cancer, clinicians should find out the EGFR mutational status and in wild type patients establish the histological subtype. These features are key to determining the correct chemotherapy regimen for that patient. One of the most exciting new drugs for lung cancer is crizotinib; this agent has been approved for use in the USA to treat patients with ALK mutated non-small cell lung cancer. However, although crizotinib has been shown to be highly effective in this group, only a small percentage of lung cancer patients are positive for the ALK mutation and these tend to be young non-smokers.

The development of ipilimumab was a hugely significant breakthrough in the treatment of melanoma and is the only drug in the last twenty years to have improved overall survival in malignant melanoma. In addition to ipilimumab, research has shown that the B-RAF inhibitor vemurafenib is associated with an extremely high response rate, is fast acting and is more effective than standard dacarbazine chemotherapy treatment. Dr Califano discusses the impact of these new agents and explains how they must be managed by clinicians.

European Multidisciplinary Cancer Congress (EMCC) 2011, 23-27 September, Stockholm

Advances in the treatment of lung cancer and melanoma

Dr Raffaele Califano – The Christie NHS Foundation Trust, Manchester, UK


Raffaele, tell us about yourself.

My name is Raffaele Califano, I’m a medical oncologist who trained in Italy and I’m currently working as a senior clinical research Fellow at the Christie Hospital in Manchester. My special interests are lung cancer, melanoma and clinical cancer research related to these two disease groups.

So you’re involved in lung and melanoma and you’re doing some clinical research. What is there to research in lung cancer, clinically?

These are very exciting times for lung cancer and melanoma because we have seen a number of excellent drugs coming up to clinical practice over the last 2-5 years, and particularly for lung and melanoma, so I consider myself very lucky to be involved with them. I’m also very lucky because I could try these drugs as part of clinical trials which have led to registration. I think the main pathway now and the main focus is about selecting the right population to be treated with the right drug. This is the only way to maximise the clinical effectiveness, trying to reduce or trying to rationalise the toxicity in this very difficult to treat population.

So non-small cell lung cancers are not all the same?

They’re definitely not the same, it’s a very heterogeneous disease and at present, before planning your treatment, you need two main measurements, without that there won’t be any tailored treatment. The first one is the EGFR mutational status whilst the other one, and this is for EGFR wild-type patients, is the histology subtype. Obviously we do know that different chemotherapy regimens have got different clinical efficacy and you need to select the right one for your patient.

And the ALK story, of course, has broken the whole thing apart in the last year or so.

That’s an amazing story because, as far as we know, FDA has approved crizotinib, which is an ALK inhibitor, for ALK mutant, non-small cell lung cancer. This is only about four years since the ALK mutation was described in the literature, which is very good from a patient care point of view and gives us, as a researcher, some further impetus to try and find good drugs and new drugs for our patients.

And crizotinib is remarkable, it’s getting 70-80% response rates. However, it’s a small percentage of lung cancer and it tends to be, if I’m right, the non-smokers, is that right?

Yes, it’s about 4% of the general population, so again it’s a small slice of the cake but it’s another small slice that’s going together with the 10% of EGFR mutant. Coming back to the ALK mutant, they’re usually young, sometimes male more than female, and never or light smokers.

Where will the next slice come from in lung? Where’s your bet?

I think the MEK inhibition is the new challenging opportunity and there are new drugs which have shown so far, probably in second line, to be something that can add to the therapeutic armamentarium. Obviously a lot of work needs to be done to select the right population to find the right drug.

And in melanoma? Ipilimumab?

Melanoma is definitely very exciting, we have two new drugs over the last year or so, the first one in terms of timing was ipilimumab, which is an anti-CTLA4 monoclonal antibody which is now FDA approved for first and second line. It’s a drug which is the only one that has shown to increase overall survival in a malignant melanoma clinical trial over the last twenty years. It’s a very powerful drug but power always comes at a price, so it’s a drug with some toxicity, especially GI or autoimmune toxicity which needs to be managed by a well-experienced team because the toxicity could be severe and the patient can experience severe problems from that, including death.

BRAF?

BRAF is the other new kid on the block. Vemurafenib is a Roche drug which is selecting inhibition of BRAF V600E mutation and has been shown to be better than DTIC in a head-to-head trial in BRAF mutant patients. The amazing thing, I’ve been involved in the trial thanks to Paul Lorigan, is that the drug works very, very quickly. I’ve seen patients in a hell of a lot of pain, on a high dose of opiates, to be pain free and not needing for any medication in less than two weeks. So we know that the drug has got a high response rate, which is about 50-55%, much better than the standard DTIC, which is between 10-20%. The data on overall survival is not ready yet, but it’s certainly very promising.

So you’re a young medical oncologist, you’ve been labelled as a rising star.

Thank you.

What are the career prospects for a young medical oncologist? Are there any?

There are, I think it’s challenging but it’s very exciting. It depends on what you like and what you want to do. I’ve always had an interest in clinical cancer research more than lab based research and this is what I would like to develop further in my career. I want to keep service provision together with clinical cancer research because I think you can use what you get from the clinical cancer experience and you can translate that into the care of your patients as a standard care.

Are there opportunities, are there jobs?

The opportunities, there are opportunities but obviously you need to look for them. I did train in Italy, as I mentioned at the beginning, and then I moved to the United Kingdom at the end of my training because I wanted to develop further experience in the field of lung cancer and melanoma and I wanted to develop my skills in clinical trials design and management. So I had the chance to apply and get a job at the Christie Hospital, which is world renowned in terms of cancer research so, so far, I’ve had a good opportunity, the team is very good, but I understand this is not for everyone, unfortunately.

And the ECCO meeting, it’s ECCO/ESMO/ESTRO, this is useful for you?

Well, I think it’s a very good opportunity because it’s a multidisciplinary meeting where all the different disciplines can come together and sit down and discuss about patient care. Obviously, the ultimate purpose is to give the best care to the patient and cancer is becoming more and more multidisciplinary. Twenty years ago the oncologists were sitting in the office and deciding which was the best treatment for the patient, nowadays they all go to the MDTs where the case is discussed and the surgeon, the radiologist, the clinical oncologist or radiotherapist and the medical oncologist will share their ideas and try to develop the best therapeutic plan for the patient. So I think this is a very good opportunity and I’m very pleased to be here.

Raffaele, thank you very much for giving us a couple of minutes on ecancer.tv.

Thank you very much.

I appreciate it, thank you.