OCTalks: Comprehensive Genomic Profiling

Freya Leask

Hello and welcome to the latest episode of OC Talks, the podcast by Oncology Central. My name is freya leask. I’m a publisher at future Science Group and I’m delighted to be joined today by Professor Michael Thomas. Michael is head of the Department of Thoracic Oncology and Internal Medicine at the Thorax Clinic Heidelberg in Germany. And today we’ll be discussing the adoption of comprehensive genomic profiling or CGP in oncology and Michael’s own experiences of implementing CGP into clinical practise. So to kick us off, Michael, could you introduce yourself? Your research background and your current research interests.

Michael Thomas

Well, as just mentioned from your side, I’m heading the Department of Thoracic Oncology at the Thorax Clinic, Heidelberg in the university environment there in Heidelberg and we care for around 1000 newly diagnosed lung cancer patients. For instance, every year in our institution. And here we provide care at best. On the one hand, on the other hand, we are involved in guideline development and eliminating and discussing algorithms for our patients at best. And saying that we have a major interest in. You know, improving standard of care in individualising treatment in oncology according to the respective patients with all the points that are important like comorbidities and social background. But of course which is the major point to stratify. Treatment according to biomarkers and to better understand, you know, what is the impact of immunotherapy in which patient groups it’s working nicely. What are the mechanisms of resistance and the same for genetically driven disease. And you know, with this frame to give you some flavour on our, you know, research capabilities and our outreach and research, we do code exploration in depth with molecular profiling and with liquid biomaterial assessments we. Transfer then hypothesis delineated from those cohort. Into preclinical models to better understand what are the mechanisms behind those findings. If we haven’t hypothesis and if possible, then we flash back into the clinics. At least 2 design trials according to the findings out of court exploration with Magnetical. Background from pre cleaning models to better understand if the idea to stratify patients would be appropriate 1 so. We move them back to the clinics and design potential Iits investigator initiated trials, according to those findings. Perhaps so far from my side to give you a feeling on my daily work, the main driver is to provide patient care at best.

Freya Leask

Fantastic. And how have you seen oncology practise evolve with the adoption of CDP’s over the past five years?

Michael Thomas

Well, if he step back five years to 2015, this has been a time when, particularly in thoracic oncology and particularly in non small cell lung cancer and the metastatic disease situation. Comprehensive genomic profiling really moved into the treatment arena. This has been the time when, for instance, in the metastatic situation it has been and it still is very important to know on molecular alterations As for instance, EGFR mutation or. Alterations EGFR. Patient has been important to know on the electric location moved in the field that time these years and all those charges that I just named and not to forget the mutation for instance offered treatment opportunity with TKI treatment tyrosine kinase inhibitor. Treatment, which provides good Disease Control to patients, good response rates taking for example the elk population and the elk positive ones which comprise 3 to 5% of patients with the adenocarcinoma Histology. If you detect those ones appropriately, you could establish a response rate of 70 to 80% to those patients, and if you sequence nowadays appropriately the TI’s that are available and provide treatment at best. For instance, if there are some metastatic sites are growing and others. Stable and you employ local regional treatment options to those you could end up with a median survival time. Approaching 70 to 80 months, which is quite tremendous for a metastatic disease scenario. So with this perspective and these statements on those molecular altered patients, knowing that if you do the, if you provide the appropriate treatment to the appropriate. Patients, strata, those patients experience a huge benefit and so genomic profiling is an absolute mandatory tool.

Freya Leask

That’s amazing. And so, in your opinion, what are the biggest benefits of CGP in an oncology practise?

Michael Thomas

With the growing evidence on the impact of molecular alterations in delineating. Or attributing patients to the appropriate treatment straight out algorithms with the increasing evidence of this impact, it became more and more important. And with this development and this scenario which we have now currently. It’s an absolute mandatory tool, at least in you know my perception and perspective. Just to explain a little bit on. Like in the very recent past, we learned on further alterations, like for instance, the ENTREC gene fusion. We learned on further alterations and the EGFR receptor like exon 20 insertions were at least in trials. Very promising treatments have been shown and I perceive that in the next year. Those treatments will make it to approval. They will become available for patients and other alteration in non fossil lung cancer, which makes it to a treatment option is the red gene fusion, for instance. So we know in the meantime something around, you know 5 to 10. Molecular alterations which segregate patients into different parts of a pie chart. And with this degradation in adenocarcinoma, you could attribute around 25% of patients as a rough estimation on molecular stratified treatment options. Which offer treatment opportunities based on tyrosine kindness, inhibition in terms of exon 20 bispecific antibodies. In addition come into the treatment scenario. Which show good tolerability. So what I would like to emphasise is that those treatment options show a good tolerability. They could be instituted in the disease trajectory even in elderly patients and patients with comorbidities. So they offer good options. They show huge efficiency and. Group disease stabilisation. As emphasised with the example of other positive patients, even on the long term. And you know, with these options in place, it’s just very important. You know that you know, is there a molecular alteration prone to such a type of treatment?

Freya Leask

It’s amazing, CGP sounds like such a powerful tool, but what are some of the current challenges that need to be overcome before CDP can be more broadly adopted as as a? With the car.

Michael Thomas

Yeah, it’s a technology which needs good expertise from the teams that provide it and dedicated teams that move into this methodology. However, providers are in the field and they. Provided good development of the technology, so I think challenges are on the one hand that there is the motivation and the decision to step onto this technology. G and then to have in place dedicated team members that become more and more familiar, how it’s managed and how to drive those platforms. And in addition, then it’s important, you know, to have skilled lab staff even on the academic level there to have a good interpretation of the results, to know how to manage the technology. If problems are evolving. So this is something you know. We will. Must gain your experience and increase your knowledge, but all these points. Could be achieved. So this is not an hurdle which could not be overcome, so it’s decision making. Yes, we would like to do it motivation to step in it to have teams available that gain their experience and make their experiences. And of course, it has to be financed, so the technology. Has its costs, but costs. As far as I observed it in the last five to eight years, the debt down, so the costs are dropping on individual patient basis and I think for the technologies as well and. So with these developments and with these market processes, I think it it would be worthwhile that this technology becomes available on a broad scaled manner to provide patient care. At best, if I reflect on a nationwide level in onto the situation in Germany, I see that there are numerous institutions that reach out on this technology that they step into that to provide Multiplex testing options on this NGS basis. Reaching out on DNA and RNA eggs to really descript in a good way the molecule landscape of disease. And if you do that upfront, taking the example of theoretical oncology and lung cancer as you do it upfront, you have then the complete information on molecular landscape and in addition that with your staging information by imaging technologies and assessing the patients with. These situation. All these points make the picture complete to individualise treatment at best, and with this statement, I think you know CGP is a very important part to provide individualised treatment with this scope. As I just stated it.

Freya Leask

Absolutely. And then you’ve you’ve talked a lot about the the potential of CGP and but could you tell me about your personal experience in implementing CGP in your own practise?

Michael Thomas

Initially I mentioned I’m situated in Heidelberg University environment, taking responsibility for directing oncology. Fortunately, we have very good and strong collaborations with the different clinical institutions on the campus and with the different clinics there. And one important institution for us with the scope on. CGB is the. Pathology department in particular molecular pathology. And the heads taking responsibility on pathology and molecular pathology and the teams in place made very early in their decisions to step onto CGP and provided very early Multiplex testing in the in the manner as I just described it and this offered. For us, very quick in order to participate and step into developments that are related to the model OCCULAR. Patients give us the opportunity to really make experiences with TGI treatments and different types of molecular alterations, and nowadays it’s very strong and very strong. And I would like to say you. Know basic tool. To phenotype and characterise the patient populations appropriately. To provide treatment at best, so experience is very good and the experience that I made in this type of collaboration was very fruitful and very fruitful, particularly for the patients to provide care and treatment at best.

Freya Leask

Fantastic and final question, how do you hope to see CDP impact the continued evolution of clinical oncology over the next five years? Yes.

Michael Thomas

Next five years, then, we will end up in in 2025. As I already stated, there is the the pie chart is becoming increasingly diverse and now it’s starting in disclaimers and non adenocarcinoma patients as well. There are even some molecular alterations which might impact on treatment in the claims Histology well. I perceive that if it comes to those molecular alterations and you employ TKI treatment, patients might experience resistance to those treatments, those they elapse. And show disease progression and this might be uncharged resistance mechanisms, which means that there is a change in the receptor confirmation due to a further molecular alteration for instance and with. Type of resistance. It’s important to have a reassessment of biomaterial like rebibbia or taking a liquid biopsy and reassess there and check OK, what’s going on there? Is there a further molecular alteration which is prone to become targeted by antibody treatment by further TKI? Treatment or other options which might arise at the horizon, like for instance immunotoxin, can you? So the development is is becoming quicker and quicker, and not only it’s becoming quicker with respect to potential tackling strategies in the resistance situation is becoming quicker. You know in diversifying the pie chart further, so I see. Her two alterations, like her two amplifications or her human mutations, which are particularly prone to toxin conjugates with very good efficiency rates in the clinic. And this is what I already perceive now. In 2020, when we look forward onto 25, I would perceive that there are further alterations prone to tackling strategies. I would perceive that the CGB technologies developed is developing. And saying that this technology isn’t might impact in the future to better delineate for instance patients that prone to benefit from immunotherapy. Because this technology could delineate proxies which help to better assess the type of tumour microenvironment interaction, offering a good interference strategy towards immunotherapy. So this is something hypothetical. Which I now state. But there are, you know, early findings out that this is something which could be brought into reality. And you know, currently there are descriptions from a conceptual standpoint to describe the tumour microenvironment interaction. And I perceive that those conceptualised reflections will move on the next level in depth in the next three to five years. And here the development of CGB technology might impact in this type of characterization as well. And there are first technologies out like whole external sequencing options with CGB which. Are now you know, in an experimental way in the clinics, but if it’s shown that this technology is working robustly and becomes available to an affordable price. This this might be something which then we will have in place in 2025.

Freya Leask

Fantastic. Well, Michael, thank you so much for joining me this evening and it was fantastic to hear your personal experience of CDP as well as the fantastic potential that has to really shape the oncology feel. Thank you to our listeners. And if you’re interested in listening to more podcasts from Oncology Central, you can visit us at www.oncology. Central.com goodbye.