European Multidisciplinary Conference in Thoracic Oncology (EMCTO) 2013

Multitarget FISH testing in lung cancer

Dr Lucas Bubendorf – Institute for Pathology, University Hospital, Basel, Switzerland

Lucas, thanks for coming. We have this situation of lung cancer has got all sorts of biomarkers and some of these are actually useful, some of them have proved useful already, some could well be useful in the future. You’ve been talking about immunohistochemistry and also FISH as testing modalities for biomarkers. Can you tell me, what are the challenges of biomarker testing?

One major challenge is the level of technical complexity and experience needed to conduct such an analysis and the availability of these techniques in the laboratories globally. The fact is that immunohistochemistry is a normal part of the diagnostic procedure in every pathology laboratory and that’s not the case for FISH, which stands for fluorescence in situ hybridization analysis.

But do you get a big benefit from FISH, from using FISH?

That totally depends on the clinical question. For example, in the ALK positive cancers that are being selected by FISH analysis, it’s the approved method of choice to select those patients for the treatment with the ALK inhibitor for the time being; it’s the FDA-approved method and it has been there before any useful IHC test has been available.

And the benefit of detecting that ALK positivity is what?

It’s a much better response to a targeted treatment of these particular patients as compared to regular chemotherapy.

So if you get your biomarker detection right, you can choose your targeted therapy right?

Absolutely, yes.

How is this going, then? Because there are treatments which are available for some biomarkers if you find them but there are other areas where you simply might not find a good treatment.

Yes, that’s true. That’s why everybody is after these new therapeutic targets that can be targeted by a specific drug. There is where most of the advance can be observed now in lung cancer where more and more of such targets and drugs pop up.

Are you making a pitch to cancer centres everywhere to get FISH installed to make it available to cancer doctors?

In many countries it’s really available; there are always a couple of centres who can provide this service.

So what is your advice to cancer doctors?

The advice is to make sure that their patients receive the testing so that the testing is available, either by the local institution, if available, or by sending it out, outsourcing this analysis to a centre where it is available.

So what’s happening now and why is this a challenge at the moment?

Of course it’s a challenge if a pathology institute doesn’t have the technology available, it’s always an additional technical hassle to send things out. So it’s the oncologist who must ask for it and discuss with his pathologist the algorithm, how they should proceed. There are suggested algorithms so patients with adenocarcinoma of the lung at advanced stage undergo testing for EGFR mutation testing. That might be something that needs to be outsourced as well if not available in an institution. If EGFR and/or KRAS mutation is negative the next step is nowadays ALK testing so a patient should receive ALK testing after that. As I said, it has been quite difficult because not everybody masters the technique of ALK FISH analysis but more and more there are ways to do it by immunohistochemistry which is more simple as a pre-screening technology to identify the patients for confirmation by FISH.

Checking for EGFR is one thing, then ALK, is that all of the decision-making tree that needs to be explored or is there more?

That’s the decision tree which I think really needs to be explored. However, if you have a young patient, EGFR, KRAS negative, ALK negative, the next step is ROS1 testing. ROS1 is a similar rearrangement like ALK and if it’s positive the patients respond to the very same drug as the ALK ones.

So are biomarkers the key to individualising therapy right now?

Yes, absolutely. The way to individualise treatment goes through the biomarkers, yes.

How much benefit could you get by getting all of this right using present day technology and present day targeted agents?

Well, the benefit is better response of the patients as compared to chemotherapy and in individual patients it’s a dramatically better response. The problem is resistance that occurs invariably after some months and then it’s the next challenge to find new markers in these patients. For the patients it’s improved quality of life, no chemotherapy - it’s usually an oral drug, these targeted treatments - and prolongation of life.

So do you see a big move over to targeted agents if you can get the biomarker analysis right?

Yes, that’s true. That’s the direction where we go now.

What’s the main message that you’d like to put over to cancer doctors everywhere coming out of this meeting here in Lugarno from your own work?

If I would be a cancer doctor, a treating physician, I would really make sure that every patient has the chance to get this testing on his tumour.

So that includes not only IHC but also FISH and some of the newer tests, maybe, in future?

Whatever is needed, so this could change on a weekly/monthly basis. Just the most appropriate testing should be applied.

Lucas, thanks very much for joining us.

You’re welcome.