COMMENTARY

Talking With Patients About NGS Testing: Marketing vs Reality

Matthew D. Hellmann, MD; H. Jack West, MD; Leena Gandhi, MD, PhD

Disclosures

May 19, 2017

H. Jack West, MD: Hi. I am Dr Jack West, a medical oncologist and the medical director of the Thoracic Oncology Program at Swedish Cancer Institute in Seattle, Washington. I am happy to be here today as part of a Medscape program with two of my colleagues: Dr Matt Hellmann, who is an assistant attending professor at Memorial Sloan Kettering Cancer Center, and Dr Leena Gandhi, who is associate professor and the director of thoracic medical oncology at NYU Medical Center here in New York.

We are going to talk about some very timely issues. One of the leading issues today in thoracic oncology and throughout all of medical oncology is the question of next-generation sequencing (NGS) and broad genomic testing of tumors. It is something that I think many [oncologists], not only in general oncology but even in academic centers, are still debating and figuring out how best to use.

Medscape did a survey that looked at the experiences of a large number of oncologists and explored their views of NGS and genomic testing and how helpful they find it. The survey has produced some interesting results that deserve some commentary.

One of the issues that has been expressed by many of the respondents in the survey was that we are not yet achieving the benefits that we would hope to get from this, or that a minority of patients can capitalize on NGS. Do you think that the conversations and the marketing of precision medicine is excessive for what we can deliver now, or how do you frame it when you talk with your patients?

Leena Gandhi, MD, PhD: I think of it in a slightly different way, which is how I talk about it to patients. I think that anything we do in cancer care has a lot of uncertainty to it about the benefit for an individual patient. I think it is more of a critical conversation about treatments. We have a lot of expectations from treatments—from immunotherapies, for example, which also had a lot of hype but still benefit a small proportion of overall patients.

The issues there are more critical, because you might be losing valuable time and adding toxicity if you are using something that is not beneficial. The test, which has a relatively much lower cost than the actual treatment, is to gather information so that we can treat patients with the most personalized information to be as effective as we possibly can, knowing the limitations and uncertainties of all of our therapy.

I talk about it with patients with the idea that we are trying to get as much information as possible about your cancer. Although we may not learn anything specific that can be used right now, it may give us information that we might be able to use later, depending on the rapid developments that are happening and other trials that are happening. I think it is always useful, and I do talk about it with patients in doing it in that context of that we are using this to gather information to build an arsenal to help treat your cancer. The downsides are relatively low compared with the downsides sometimes of the therapies that we use for patients.

Dr West: You bring up the issue, and we have tangentially mentioned it in earlier points, that the cost of the test is really not the lion's share compared with the impact of longitudinal treatments with expensive drugs. Are you concerned about having seen a pattern where people get a report back that says this or that rare mutation may respond to this or that drug (everolimus, perhaps), on the basis of preclinical work, and the patient and/or the doctors say, let's not do conventional chemotherapy because the precision medicine test says let's use this targeted therapy? Here you are talking about potential toxicities and costs without there being a base of clinical data. Is that a concern, a downside of potentially replacing established effective therapies with more whimsical or speculative approaches?

Matthew D. Hellmann, MD: There can be ways in which the information that is provided by the reports from NGS testing may be stepping ahead of the information that we [already] have that reliably informs therapeutic options. The everolimus example is a good one; I think it commonly is listed as a therapeutic option for patients but rarely is very well-informed. I think that can be adjusted in the conversation of what is the right amount of information to put on reports and an opportunity for improvement so that it does not put patients in the situation of feeling emotionally hijacked by the need to go get this treatment that really could work. In our hearts and our information, we know that that is probably not the case. I think that that is a place where information can be optimized.

 
Anyone who has treated a patient with an ALK rearrangement who has responded dramatically to crizotinib or alectinib knows how amazing this can be.
 

We also should not be too pessimistic about the progress that we have made in the context of precision medicine. Over the past decade, we've identified a good half-dozen targets that reasonably have therapeutic options—that is really profound, and one that other diseases are continuing to try to catch up with and understand the underlying molecular biology of the given cancer. Anyone who has treated a patient with an ALK rearrangement who has responded dramatically to crizotinib or alectinib knows how amazing this can be. We should not lose sight of just how much progress we have made, and the opportunities for advancement, of course, are there. This has been a tremendous achievement, and we should not diminish that.

Dr West: Even if it is 1%, 2%, or 4% of the time, the fact that you are potentially able to treat patients who are going to have profound benefits that can last many months, even extend into years, is a different paradigm than we have seen before.

Dr Hellmann: Look at the median survival of patients with ALK rearrangements, it is now 4+ years, and is a tremendous advance relative to previous times. Our opportunity and challenge in treating patients with lung cancer is that there are so many patients with lung cancer that even if we are able to identify 4% of patients who can benefit from a new drug, that is tens of thousands of patients and exceeds the number of other cancers entirely. Identifying rare targets is extraordinarily important for patients with lung cancer, just for the sheer magnitude of the disease.

 
Identifying rare targets is extraordinarily important for patients with lung cancer, just for the sheer magnitude of the disease.
 

Dr Gandhi: I completely agree with that. I think one of the problems, though, that we have not discussed and which I think is the biggest problem of NGS testing is that the more you look with greater depth and greater breadth, the more you find. It is not uncommon, especially with the larger panels, that we see multiple different abnormalities of unclear significance. It is hard to know sometimes which are passenger changes and which are relevant drivers of cancer, and it is something that we really struggle with.

Certainly, at major centers, we see patients all the time who come in for clinical trials because of one out of five things that were listed on a report. It is very hard to know, in that broader context, how useful targeting this one thing out of these five is. Something we still, as a community in research, have to grapple with is understanding how to integrate multiple findings and what their implications are.

Dr West: One area of common ground, even among some of the skeptics who responded saying that NGS is of limited utility now, is that almost everybody agrees that it is going to be paying greater dividends in the future. I think that if we are talking about a half-dozen or eight potential targets now, it is quite likely that in 3 or 5 years, that number is going to be greater. The proportion of patients will be greater. I think we probably all agree that NGS will be of much less debatable utility. It will be "how did we live without this?" in the next few years.

Thank you very much to my colleagues here, Drs Leena Gandhi and Matt Hellmann. We will have more to talk about in the coming years.

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