Supplements and Featured Publications
Adam Fox, MD, discusses the need for molecular profiling in non–small cell lung cancer and how these results factor into multidisciplinary planning.
With the growing role of targeted therapy in the perioperative setting for patients with non–small cell lung cancer (NSCLC), conducting molecular profiling via next-generation sequencing (NGS) has become imperative across different stages of disease—including the resectable and metastatic settings—for this patient population, according to Adam Fox, MD.
“[Molecular] testing rates are probably improving slowly year to year. There’s a lot of over-optimism about how fast it’s being performed and how much testing is completed before therapy, so I would urge people in their local practices to ask their colleagues how long testing takes,” Fox said in an interview with OncLive®. “We learned a lot from our processes [at the Medical University of South Carolina] in the last couple of years, and we are still learning. I would challenge the community to look internally at their own processes and ask around [about processes of others], and I’m sure you’ll find opportunities to improve [these processes] in almost every system.”
In the interview, Fox detailed the importance of conducting NGS testing at diagnosis for patients with NSCLC, the potential role of retesting in the event of disease progression or recurrence, and barriers that still need to be addressed regarding access and timing of this testing.
Fox is an assistant professor in the Department of Medicine in the College of Medicine at the Medical University of South Carolina (MUSC) in Charleston.
Fox: It’s becoming more essential for most patients with NSCLC to get biomarker testing or genomic profiling, ideally at the time of diagnosis. In the last decade, it started off with just testing at the time of diagnosis for [patients with] metastatic disease. As we’ve seen more data and trials come out, [testing is] extending lower and lower into the earlier stages [of disease, meaning for] people who are candidates for resection, especially to determine whether they need therapy before or after surgery to improve [outcomes] such as survival. The outcomes are robust for these data, and [it is critical to conduct testing to inform] these decisions for systemic therapy before or after surgery in the early stages, [as well as] in more advanced stages where surgery is not an option.
This is an area of research [interest] for me, [looking at] how individuals use biomarker testing in lung cancer. How comprehensive [is the testing]? How often [is it conducted]? What is the timing and how long does it take? In the earlier stages, we don’t have a lot of data for how individuals [conduct this testing].
Locally, we’re very aggressive about trying to get biomarker testing before treatment decisions are made. We may often have a tumor board discussion where the default is neoadjuvant chemoimmunotherapy before surgery, but [this decision] is usually pending biomarker testing. We’re having these discussions early, and if an actionable mutation is found—especially one that would preclude response to immunotherapy—we often pivot to change [course of treatment].
There are some survey data out there about the number of people pursuing repeat biopsies. Oftentimes, it depends on what mutations patients start with [at diagnosis] and what treatments they’ve received [to determine] whether they need an updated test.
However, we’re seeing [repeat testing] more, especially as patients survive longer and longer with the various treatments that they now have available to them. Over my short time [practicing] outside of fellowship training, we have seen more [repeat molecular testing] vs what was historically seen, because we have so many more options for treatment now. Every year, we have new indications, new biomarkers, or new drug classes coming out, and that is driving the need for testing and repeat testing.
Just as we’re seeing more options from a systemic therapy standpoint, we’re seeing more options to combine those [treatments] with other modalities. It’s almost unusual these days—outside of the earliest stage I lung cancers—[to not consider] multimodal therapy between either surgery, radiation, or a systemic therapy or combination of systemic therapies. [Multimodal approaches] are increasingly common, and we do hear anecdotes from around [South Carolina] and around the country that the inability to coordinate and plan these treatments is a huge barrier to guideline-concordant care, or appropriate care.
We sometimes hear that medical oncologists will start a neoadjuvant approach for patients who don’t ever make it to surgery and never saw a surgeon. We’ll see other kinds of discoordination logistically. I’m fortunate to work in an academic medical center where [different specialists] are in a single cancer center on a single day. However, oftentimes the logistical practicality of collaboration is hard when you’ve got multiple practices not under a single roof. Having a tumor board and a space where people come together to discuss the plan moving forward at an early stage helps streamline that care and make it consolidated.
This is an area that is deeply interesting to me as a health services researcher. The question is: does everyone need NGS? It’s become the standard of care in [the US], especially in the metastatic stage, but in earlier stages, there’s a big question, because [NGS] does take time, it does cost money, and not all of those results may be needed before a surgical approach with or without systemic therapy is determined. There are probably places that are not doing NGS in the early stage and rather are doing more targeted testing [at this time].
In terms of ordering these tests, when I go to conferences and talk to people about lung cancer, one of my first and favorite questions to always ask is, who orders biomarker testing, how does it get done, and how do you do it? I’ve never heard the same answer twice. It’s always a different logistical step, and it comes down to the complexity of the issue in the different contexts of different medical centers and practices. I believe that we should have a coordinated plan for biomarker testing at the time of diagnosis, whether that’s myself ordering it, which before I helped set up a reflex testing program at MUSC, that was how all of my patients got tested, as I attempted to order [the tests] as soon as I could when I knew it was appropriate. However, in other places, logistics don’t work out for that. Pathologists may or may not be OK with ordering them for different compliance reasons and medical/legal reasons.
However, I think most people can agree that the last person who should be ordering it is the medical oncologist at the time of their first visit. That’s too late. We’ve wasted a lot of time if [a patient] is showing up to a medical oncologist’s office and biomarker testing hasn’t at least been started. We’ve been looking at some currently under-review data with a national commercial laboratory, and we were able to measure how long it takes for the biomarker test to be ordered. It takes about 2 weeks from the time of biopsy, on average, to when biomarker testing is ordered. In my mind, there are a few days in there in which the pathologic diagnosis is being rendered, but the rest of it is just wasted time for a patient who we know is going to need biomarker testing. Trying to set [molecular testing] to be a systematic or automatic process is important.
There needs to be a continued awareness among all specialties about the implications of [molecular] testing, especially those who don’t deliver treatments, such as pulmonologists. That’s an area that I’ve been investigating over the last couple years. There needs to be continued policy efforts around testing and reimbursement. A lot of the commercial vendors of this testing have offered to help with the barriers of cost, and it’s important for people to engage with whomever they’re getting testing with to make sure that [cost] is not an issue. Oftentimes, there are patient relief programs in place that can be helpful.
A lot of [barriers are tied to] logistics. [Molecular testing] is a lot of extra potential logistical work to cancer care. With lung cancer being one of the most common and most deadly cancers, there’s not only a volume issue; there is also a time-crunch issue. If you look at metastatic [stage IV] lung cancer, approximately [30%] of patients are deceased at 90 days.2 With the time it takes to diagnose, get biomarker testing, refer patients, and then get set up for a therapy, that takes a lot of time. There is an urgency that needs to be relayed across specialties, especially in lung cancer. Generally, medical oncologists, [including] those at both academic and community centers. [understand this urgency]. It’s the other [specialists] supporting the medical oncology community that need to be aware of how urgent this process is.
