Future Directions in Precision Medicine: An Evolving Treatment Landscape


Closing out their discussion on biomarkers and precision medicine in cancer care, key opinion leaders look toward future evolutions in the oncology landscape.

Samuel K. Caughron, MD, FCAP:
Biomarker testing is going to continue to be a cornerstone of testing, especially to guide patient treatment. There are some exciting advances coming, like the ability to integrate more than a single biomarker finding when developing a treatment plan. We are still early in our understanding of how biomarkers impact treatment options, and how multiple biomarkers interact for significance to a patient. I think it's going to be very exciting as we begin to look at how multiple biomarkers are impacting one another, and the potential benefit or lack of benefit from different treatment options. I think that's going to be the next major step that this space has moving forward.

Timothy J. Pluard, MD:What are your thoughts on where you see the future going in terms of biomarker testing and what do we look for down the road?

Sujith R. Kalmadi, MD: I think the next step, obviously, is RNSC, which is probably going to become the standard of care for most tissue platforms. Number 2, I think full genomic profiling is around the corner and that's probably 5 to 7 years away from integrating it into clinical practice. Those two things are going to happen. I was thinking that the splicer technology, CAR-T, and all of these would drive that even faster. I think we're probably about 5 to 7 years away from all genomes being incorporated into treatments.

Ossama Tawfik, MD: I agree. I really think this is around the corner and there are people who are trying to really bridge the gap of how to make it successfully, cheaper, and faster in real time that you guys can get the information that you need instead of waiting patiently for us to provide you with the data. I would also say that back to the collective scientific community, it's really important for all the agents, the pathology societies, the oncology societies, and the pharmaceutical companies to get together and build trust and create opportunities for us to make it better, because it is the future. We are all believing that this is going to be happening, but it has to be faster, cheaper, and better.

Timothy J. Pluard, MD:I agree, and I think from my perspective, probably the biggest challenge going forward, is with genomic testing but also in a lot of other clinical situations in medicine, it's really how can we harness the big data, the huge amounts of data that we're getting. Are we going to reach the point soon, if we haven't already, where we've identified most of the low- hanging fruit, the single gene mutations that are drivers? Do we have to start to integrate our knowledge of pathways, oncogenic pathways, and identify combined mutations or abnormalities that may be causing a particular pathway to be hyperactive and driving the cancer?

Sujith R. Kalmadi, MD: I think all of that is very important, but I think we cannot still forget about regular pathology. I'll give you an instance. It took us 15 to 20 years, maybe, to perfect the Allred score and figure out who is ER-positive and who is ER-negative. Even today, there is debate about it being 10%, 5%, or 1% in the adjuvant setting. So, we still haven't answered those kinds of questions. Those all come back into play.

For instance, one of the biggest challenges I'm running into in clinical pathology is with the recent approval of Verzenio and the testing to see the Ki-67 score. You'd think by now we would have figured out how to do a Ki-67 score, which has been around for 30 to 40 years, but we still don't know how to do it. There's a shortage of the agent and we don't know which patients to put on treatment and which ones not to put on treatment so those kinds of things are still very relevant, I think.

Timothy J. Pluard, MD:I think you're absolutely right. I'd really like to hear your thoughts on this. We're using HER2 IHC to identify now 0 versus 1 when the assay really wasn't optimized for that. It was really optimized to try and find the HER2-positive patients, and now we're asking the pathologist to go back and relook. Was that 0 really 0? As we know, IHC 0 may not be truly complete absence of any HER2 staining, right?

Ossama Tawfik, MD: I am very much interested in this because about 20-plus years ago I started doing IHC on HER2 and compared it by digital image analysis and compared it with FISH results. We were having the debate which one of us is better, and at the time, digital image analysis was not even available. I was lucky having a system next door to me, so I said, I will try theimage analysis to accurately diagnose positive HER2. It was a dichotomous test, positive or negative or in between. With 2 plus, you do FISH and you solve problems. We have undergone evolution between ASCO and CAB guidelines, especially with updating it.

It was 2013, 2018, and now, 2022, that we're going to be updating again for the HER1 low because we, pathologists, were saying, if it is negative why do you worry about a blush on the slide that I can call it 0 or call it 1? Nobody cared and everybody was happy. Life has changed and has become very complicated. With having interest in HER2, I started pulling back slides and reviewing them. Sure enough, we have about somewhere between 10% to 15% discrepancy either way. The HER2 zero, there are a few cases about 10% to 15% that I could have called them with the new way, one plus, but I didn't care, I wasn't experienced enough, or I was in a hurry. I'm not hurting the patient so I'm not doing anything wrong. On the other hand, some of the one-plus cases have people that were aggressive enough and some were not that aggressive but were not accurate. The test, as you mentioned, is not designed to address this new challenge. We're trying to tweak it. We think we can do it and I believe we can do it. It's just a matter of time and we're going to be trained. Roche is doing a very good job now in tweaking the testing also on their platform which will help us in making the changes, and we're getting there but it's a process.

Timothy J. Pluard, MD: Great, well I want to thank you both for the engaging conversation. I think, if I had to say the one take-away message, is that we're blurring the lines between pathologists and clinicians at the bedside. We need to really work hand-in-hand to really optimize identification and utilization of molecular testing to benefit our patients.

Transcript edited for clarity.

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