Johnson Drives Home the Importance of Biomarker Testing in Lung Cancer

Melissa L. Johnson, MD

One of the reverberating themes of 2021 that should carry into 2022 is the importance of molecular testing, said Melissa L. Johnson, MD, who added that next-generation sequencing (NGS) can identify rare mutations for which there are an increasing number of available treatments.

“As I reflect on our Institutional Perspectives in Cancer [IPC] webinar presentations, I realize how much more complicated the care of [patients with] lung cancer has become with all these new strategies. Yet we are developing guidelines and pathways and avenues with which to care for our patients. You need PD-L1 testing and NGS testing, and those either open or close doors in terms of treatment,” Johnson said in an interview with OncLive^® during an IPC webinar on lung cancer, which she cochaired.

Johnson, who is program director of Lung Cancer Research and lead of the Solid Tumor Immune Effector Cellular Therapy Program at Sarah Cannon Research Institute in Nashville, Tennessee, discussed the focus of each presentation. The presentations centered on immunotherapy vs chemoimmunotherapy in the frontline metastatic setting, surgical perspective of treatment in early-stage non–small cell lung cancer (NSCLC), best practices for molecular testing, and EGFR-, RET-, and KRAS- targeted therapies for patients with advanced disease.

OncLive^®: How have the FDA approvals of targeted therapies in 2021 underscored the importance of molecular testing?

Johnson: At the IPC, I talked about the targeted therapies that have led to FDA approvals during 2021. I included selpercatinib [Retevmo] and pralsetinib [Gavreto], which were approved in late 2020, as well as sotorasib [Lumakras], which [was approved in 2021]. I also talked about amivantamab- vmjw [Rybrevant], as well as mobocertinib [Exkivity], which also gained approvals during 2021, and followed it up with a discussion of adjuvant osimertinib [Tagrisso]. When I received the topic [of EGFR targeted therapies to present], I thought that all those mutations were sort of a disparate group. What I realized is [that] each of those mutations [may be found in] just a few patients, but together, it comprises quite a big group of patients with lung cancer.

The take-home lesson for my presentation was the importance of molecular profiling. When we do NGS testing, we’re not always sure what we’re going to find. In the past, when we were evaluating selpercatinib at Sarah Cannon, for example, many of the doctors would say, well, 1% of lung cancer RET rearrangements are so uncommon, I’m not going to see those. But you don’t know whether you’re going to find a RET alteration or maybe a KRAS mutation, which occurs in 30% of patients. In 30% of those KRAS mutations, we see G12C. All of that to say: we’re learning as we go. We also talked about getting those results faster. How can we bring patients to their most appropriate therapies sooner? That should be some of the focus of 2022. We know these tools are important. How do we utilize them with more efficiency?

That becomes important when we move into the adjuvant space. We are still discussing with our pathologists how we test for EGFR and other alterations in the adjuvant setting if [these targeted therapies are] not all approved [in that setting]. Here again, the same take-home lesson is applicable. Yes, EGFR L858R mutations and exon 19 [deletions] will only be found in 10% to 15% of patients after their surgery. For those patients, osimertinib is really going to improve their disease-free survival, and likely overall survival, although we don’t have those results yet. Coming soon are all the other targeted agents I talked about in the metastatic setting that we’re going to move into the adjuvant setting and to early-stage disease. NGS testing is going to be as important for early-stage disease as it is currently for patients with metastatic disease.

You also discussed targeted therapies for patients with EGFR exon 20 insertions. What distinguishes the 2 newly approved agents?

I also talked about new drugs in the metastatic setting for patients with EGFR exon 20 insertions. Here again, [this subset comprises] a small group of patients. In general, doctors will say to me, I’m not seeing that or I see that once a year. But remember, you don’t know what you’re going to find when you do the testing. We saw 2 new approvals during 2021 for patients with EGFR exon 20 insertions: amivantamab, which is an intravenous drug given with a loading dose followed by once-every-2-weeks [dosing], as well as mobocertinib, which is an oral drug given daily. These drugs have very different safety profiles, and they’re administered very differently. They’re probably going to be a good fit for different groups of patients. It was important to begin to talk about the differences in the profiles of the drugs and how you might choose for your patient which drug is the best match.

Your co-chair, David Spigel, MD, of Sarah Cannon Research Institute, spoke about frontline treatment regimens for patients without oncogenic drivers. What is being used to drive treatment decisions, and what do you see playing a larger role in these decisions moving forward?

Dr Spigel gave a great presentation on frontline immunotherapy vs chemotherapy options. He reviewed all the options that exist, including chemotherapy plus pembrolizumab [Keytruda]. We now also have chemotherapy plus nivolumab [Opdivo] and ipilimumab [Yervoy], nivolumab plus ipilimumab alone, as well as PD-1 monotherapy in pembrolizumab, atezolizumab [Tecentriq], and cemiplimab-rwlc [Libtayo], which are all approved for patients in the frontline setting.

The challenge is how do you select [a regimen] for your patient? We talked through some of the biomarkers: PD-L1, tumor mutational burden, and molecular profiling, [all of which] we use to assign therapies. There are some [regimens], we think, that are more effective for patients with squamous histology, and others that may be more effective for patients with nonsquamous histology. That’s a new theme that reverberated at the end of 2021, that there is a difference in how patients with squamous lung cancer respond to immune therapy compared with those with nonsquamous lung cancer. I predict that there will be more discussion of this in 2022. All of that to say, there is no wrong option, but we as oncologists have the sense that there probably is a better option for each patient. We spent some time discussing that for patients with metastatic disease as well as in the early-stage setting as these drugs and immunotherapy and chemotherapy combinations gain approval for patients in the neoadjuvant and adjuvant spaces as well.

Denis Gilmore, MD, of TriStar Medical Group, discussed early-stage NSCLC from the surgical perspective. How has the dynamic changed between medical oncologists and surgical oncologists in this setting?

Dr Gilmore has been with us for several years at TriStar Centennial [Medical Center] and Sarah Cannon. It was great to hear his perspective. There’s no debate among medical oncologists about the importance of moving immunotherapy and chemotherapy into the neoadjuvant care of patients with early-stage disease. The surgeons, who are the ones seeing these patients initially, are a group that we need to work on educating in the next year or two. Our surgeons at our hospital are used to us asking whether we can put a patient on a trial and get a little therapy in advance of them taking the patient to the operating room, but that’s a message that probably needs to be repeated and expanded upon.

The CheckMate 816 trial [NCT02998528] data that Dr Gilmore presented [were] a great illustration of why [we need to get patients on systemic therapy before surgery]. The pathologic complete response rates were better when immunotherapy was added to chemotherapy. The major pathologic response rates were better when immunotherapy was added to chemotherapy. Probably even more importantly, the surgical outcomes were improved, including the length of stay, the morbidity associated with the operation, and how much normal lung had to be taken out. There were several measures that surgeons care about that were reported. Dr Gilmore went through them very nicely. We had a great multidisciplinary discussion. I was proud to showcase that because it shows the new discussions that are taking place at tumor boards across the country. For those who are starting to have those conversations with their thoracic surgeons, it probably gave them some talking points to begin to discuss regarding adjuvant atezolizumab as well as chemoimmunotherapy, which we know is coming.

Andrew McKenzie, PhD, of Sarah Cannon Research Institute, spotlighted best practices for molecular testing. How did he emphasize the importance of testing in the current era?

Dr McKenzie also joined us at our IPC. I love when Dr McKenzie participates, because he really has a way of driving home the importance of molecular testing. He talked about several key aspects of testing tissue vs plasma, sequential testing, as well as how you can use those results in the care of your patients. He is a critical leader at Sarah Cannon who oversees our personalized medicine program and spends time talking to doctors about what targeted options to use in the care of their patients. He brought all of that with him in his presentation, which is just as good as it always is and was one of the favorites from the event, I’m sure.