Examining Trends of Biomarker Testing With the MYLUNG Study in mNSCLC

The MYLUNG Consortium looks to examine patient factors associated with the rates of biomarker testing with the goal of identifying the trends in testing rates to discover ways they could be advanced, specifically in patients with metastatic non–small cell lung cancer (mNSCLC).

Providers and investigators from The Network, US Oncology Research, and Ontada were united through this trial in a joint effort to improve precision medicine for lung cancer. MYLUNG consists of 3 protocols: Protocol 1 which examines Ontada’s real-world data from electronic health records, protocol 2 which will observe factors and events that determine a patient’s first-line treatment selection, and protocol 3 which will enable prospective and operational interventions by taking the findings of the first 2 protocols into account.

The study included a total of 3474 adults with a median age of 69 years (range 23-90). Among those enrolled, 51% were female, 65% were White, 8% Black or African American, and 46% were treated in the South United States census region. Histologies included in the study were adenocarcinoma (74%) and squamous cell carcinoma (19%). Further, biomarkers included were EGFR, ALK, ROS1, BRAF, and NTRK.

Overall, findings showed that lower comprehensive biomarker testing rates were significantly associated with that Black or African American patients (Odds Ratio [OR] 0.71; 95% Cl, 0.54-0.93, P =0.01) those from a smaller practice sizes (OR 0.84; 95% Cl, 0.68-1.04, P =0.11), Southern practices (OR 2.04; CI 1.24-3.34, P =0.005), and patients with squamous cell histology (OR 1.76; 95% 1.33-3.23,P <0.0001).

Further understanding of the clinical and social determinants of health will be important when evaluating interventions to improve testing rates in the prospective phases of the MYLUNG study.

During an interview with Targeted Oncology^TM, Nicholas J. Robert, MD, an oncologist at US Oncology Network and the vice president of Medical Affairs, Ontada, further discussed the data of the MYLUNG study which he presented in a poster at the 2022 American Society of Clinical Oncology Annual Meeting (ASCO).

TARGETED ONCOLOGY: At ASCO this year, you presented a poster of the predictors of biomarker testing among patients with mNSCLC. Can you explain the methods of the study?

Robert: The poster looked at the indicators of who had biomarkers done in the setting of metastatic non-small cell lung cancer. We looked at 3500 patients over a 2-year period, starting in March 2018-April 2020. We looked to see if patients were having biomarkers which are important to evaluate what treatment options a patient has with metastatic non-small cell lung cancer.

We reported that if you did the whole panel, which were 5 biomarkers, this occurred about 46% of the time. It should be happening around 90% plus, so 46% is not a great number. The good news was that this part of the MYLUNG Consortium is so-called protocol 1, and we are doing protocol 2, which is looking at patients in a prospective fashion. Then protocol 3 will be interventions.

With that information, what we then did was [look at] the indicators, and the poster goes over a number of variables like age, gender, ECOG, performance status, stage at presentation, but we also looked at other variables which came out to be meaningful in a multivariate predictive model. They were [that] African Americans were less tested than non-African Americans. The histology squamous was less tested, and that makes a lot of sense, because the biomarker really started with adenocarcinoma, which is a non-squamous histology.

Then we found that patients that were seen in practices saw more patients than patients who were seen in practices who saw less patients with metastatic non-small cell lung cancer. There are less patients with a complete biomarker panel, which also makes sense. If you do something a lot, chances are, you'll probably do a bit better than if you do something less often. Lastly, we looked at albumin, a protein measured in the blood, and there is an association with low albumin and poor performance status. That makes sense for patients that we're not good candidates for complete evaluation that didn't have these tests done.

With this information, we will have a better idea of how to intervene moving forward. Protocol 2, the prospective protocol, is collecting more variables around social determinants of health. We hope from protocol 2 to have additional insights, and then we'll use those insights to design interventions in protocol 3. Protocol 2 has 1000 patients, [and] we expect to finish the approval by sometime this summer.

What baseline characteristics were patients required to have in order to be enrolled in the trial?

All of the patients had to have metastatic non-small cell lung cancer and they all had to be initiated on some form of treatment during that 2-year period. We had to have access to the biopsy results, and then some patients got tested with these biomarkers, and some did not. Some had 1 test, some had a few tests, but only 46% had all 5 tests, which we considered the comprehensive panel at the time.

Can you explain next-generation sequencing and how it plays a role in your research?

Today, it's about 10 biomarkers, so it's grown since then, which argues for using a certain diagnostic platform called next-generation sequencing. That's a more recent method for assessing mutations and other gene abnormalities. The advantage of that is that you can do a panel of hundreds of genes. As more gene mutations become actionable, by that I mean they become targets for different therapies, it makes more sense to use something that's a wide panel like next-generation sequencing.

The good news is that from protocol 1, we did find an increase in next-generation testing, and we have an impression from protocol 2, the data has not been all analyzed and collected, but we are seeing that trend continue.

What were the key takeaways of your research?

The takeaways are that in this population of about 3500 patients, all had metastatic non-small cell lung cancer, and all had received some systemic therapy. Patients who didn't receive any treatment, maybe very advanced disease, poor performance, status, elderly, whatever, they're not included, but that's only a small number of patients. The issue was that they had biomarker testing done, and there were 5 biomarkers that we looked at which were considered the appropriate biomarkers, which was recommended by guideline groups to be tested. We found that only 46% of those patients had all 5 biomarkers. Then we looked at indicators that predicted who was getting tested.

We looked at a list of variables like age, gender, initial stage, performance status, and what we found, because we also looked at race, was that African Americans were less tested. We looked at histology and we found that patients with squamous histology are less tested. We expected that to change a bit because for a while, it was a little unclear from the guidelines whether you should test squamous, but we are seeing more squamous cells [patients] being tested, especially with the increased biomarkers. The other category was practice size, so patients that see less lung cancer did less complete panel testing. Lastly, albumin, lower albumin which we think is related to poor performance status, is less testing.

I think it's important to say that we are not happy with these results, and we are not happy with the 46%, and we're not happy, especially [because] racism appears to be a factor. The other thing is region. The South, for unclear reasons, had less testing. Now, you can argue there are more African Americans in the South, but this was a multivariate analysis so that was taken into account.

What do you think will be interesting to see with future research in this space?

I think it will be interesting to see findings from protocol 2, which is prospective, because that will lay the foundation for protocol 3 of the MYLUNG Consortium about interventions so that we look out for those groups that were less tested and alert physicians. Also, there's probably an educational issue. Although this is a little bit different from what is going on a clinical trial or even getting the vaccine, these are patients who have metastatic non-small cell lung cancer, and I think if the patient's heard that, there might be some value in getting these biomarkers done because it could have an impact on their treatment.

I think everyone will agree that there may be a financial issue, but I don't think there's an issue about the value of the testing. One thing [that is] important is these biomarkers, if they're positive, they provide the patient with more customized treatment. Some of these biomarkers, instead of getting a standard chemotherapy or chemoimmunotherapy, they can get a pill that is targeted to their tumor and the side effect profile tends to be more favorable.

One example is, if you have a mutation for one of the biomarkers called EGFR, epidermal growth factor, the treatment produces outcomes where you're controlling your disease for [about] 11 months compared to chemotherapy, which is about 4 months. The other part is that probably best for the gene biomarkers, there are only about 30% of patients that will be positive for one of those, so 70% will not be for the gene biomarkers. There are 5 and for 1 that's not a gene biomarker, PD-L1, so, it doesn't mean don't test because for those patients that are positive, the treatment can be dramatic.

How do you think this research will influence future practices?

I think one of the things is [when] we raise awareness among our practices and our physicians, and we are seeing this, more testing is occurring. The platform, this next-generation sequencing, is what we think is the best platform. It also gives us a chance to find other gene mutations that could be a potential target for a clinical trial.

Lastly, making sure that we test everything, and realizing that there may be some patients that don't get tested. For example, financial barriers, if the tests lead to a copay of $1,000, for some people, that may be something they can't afford. It's important for them to hear that if they end up with one of these gene mutations, they could get more effective therapy. Then it's a cost issue. US Oncology works very hard to understand the financial situation of our patients. My suspicion is [for] the majority of patients, it's not the finances, it is more awareness. Awareness among physicians and certainly awareness among patients.

Reference:

1. Robert NJ, Chen L, Espirito JL, et al. Predictors of biomarker testing among patients (pts) with metastatic non–small cell lung cancer (mNSCLC). J Clin Oncol. 2022;40 (suppl 16)9130. doi: 10.1200/JCO.2022.40.16_suppl.9130