Precision Medicine is Changing Lung Cancer Treatment, But More Studies are Needed

Robert Coleman, MD

Mutations and precision medicine are changing how lung cancer is treated, especially as molecular testing becomes more common place, and a greater number of mutations are identified.

According to Robert Coleman, the US Oncology Network's cheif scientific officer, mutations such as EGFR and KRAS have changed the therapy space. Increased molecular testing has allowed for more specific and targeted therapies, improving outcomes.

However, challenges still remain even as more mutations are identified. For example, clinical trial enrollment tends to limit and excludes patients with high-risk disease. Patients with another primary illness or those with specific comorbidities tend to be excluded, limiting the patient pool drastically. Real-world research and evidence is needed to fill this gap, and Coleman and his colleagues at the US Oncology Network are working to fill this gap with the MYLUNG consortium pragmatic study.

The most recent data from MYLUNG were presented during the American Society of Clinical Oncology Annual Meeting and showed that most patients received at least 1 biomarker test before their frontline treatment, but fewer than 50% of them received all the 5 biomarker tests recommended to make a good decision on treatment selection. The tests that all patients should receive include ALK, BRAF, EGFR, ROS1, and PD-L1. This research underscores a need to improve testing in the field.

In an interview with Targeted Oncology™, Coleman, discussed the evolving treatment paradigm of lung cancer and the role of molecular testing now and in the future. 

TARGETED ONCOLOGY™: Which groups of patients are most in need of research?

COLEMAN: All patients are in need of research. I But I do think that there are specific cohorts of patients that are either disenfranchised, or have eligibility restrictions to try to increase the precision of the interpretation of the trials. Because of that, it restricts some patients, with for instance, comorbidities, which may or may not be relevant, specifically, but they're called out because of potential risks in confounding the data. Obviously, patients with comorbidities, patients at the spectrums of ages, patients at the spectrums of performance status, patients with specific kinds of concomitant medications, patients with prior treatment, different types of prior treatments. And one of the biggest ones is patients with a with another primary. It's not uncommon for gynecologic oncology patients to have a history of breast cancer or colon cancer, because the age groups kind of overlap. So, I do think that we can learn a lot from our real-world evidence type of trials if they're carefully conducted to broaden the applicability of a research study that's conducted under restricted criteria to a broader population.

What are the key takeaways from the presentations you gave during the ACCC Annual Meeting?

I had 2 presentations. The first one is about how we incorporate these molecular testing precision medicine, and how what impact that has had on patient lives. I'm obviously very concerned that we have way more clinically relevant questions then we have patients to test them on, because the participation rate on clinical trials is so low. What we're trying to do is to build a portfolio menu of trials that can address these questions, allowing for flexibilities in design, as we already mentioned, but also to be knowledgeable about the fact that the clinical field is following the science carefully. As we broaden our understanding of the molecular determinants of disease and match drugs and therapeutic strategies that are aligned with this, will will have an understanding of the best opportunity to improve outcomes in patients. I provided that lecture about 1 of those strategies that we're trying to execute in the real world, which is a program called MYLUNG.

My second presentation was to provide a little bit of background about why we did this trial. And it's a series of trials under a program. The focus of this is to provide that quantitative and qualitative information to the patient and the physician in making a decision about their first line therapy for advanced stage lung cancer. So we believe that with respect to the importance of molecular annotation, that as this information becomes more available, we want to put it in the hands of doctors early on in their treatment plan so that they can come up with the best treatment for the patients.

In terms of precision medicine, what are some of the key advances that we've seen in lung cancer recently?

Lung cancer has kind of been the poster child of this. Over the last several months, we've seen more and more approvals aligned with specific molecular alterations. These alterations are not big components of the total picture of lung cancer, with the exception of, for instance, EGFR mutation. But what we're seeing are 2 things. The first thing is that treatment for these molecular adaptations like EGFR mutation, which are already approved in other disease settings, are being moved earlier in the treatment paradigm. So that's an impressive and important finding. But we're also finding aspects such as ROS1 and MET and RET and expansion of our immunotherapy single agents and combinations are being moved into earlier and earlier lines of therapy.

This year, a lot of focus has been on the G12C, which is the KRAS mutation for which there's been a lot of interest and hopefully an approval coming very soon. It’s been exciting to watch that these trials are providing clinically relevant information about their activity in our patient population. And we're taking that information and moving it earlier into the treatment paradigm.

Would you say that implementation of precision medicine is done widely across the lung cancer field? Is there a difference in the community oncology setting?

I don't think there's so much of a difference in the community oncology settings. I do think that most of the physicians who treat lung cancer are basically up to speed or are participating in these trials. The knowledge gap there, I don't see that as huge. However, lung cancer isn't always taken care of by people that are key opinion leaders in lung cancer. And so, a strategy that is a focus of the MYLUNG program is to try to normalize the wide variance of quantitative molecular orientation for newly diagnosed patients. Over the last several years, there's been multiple publications that show for the five most common molecular alterations, the rate of essentially unknown, meaning that it was an unknown by the time the first decision was made, it was about 70%, a very high number. With the advancement of education, and in turnaround times for molecular testing, strategies to optimize the tissue journey, and patient education, these kinds of factors have now started to impact that and how much of that testing has been used for treatment.

What presented during ASCO this year is that within the US Oncology Network, those numbers are substantially reversed. Actually, we have a much higher rate of at least something known. Over 85% of the time, something is known at the time of the initial treatment decision. We're trying to expand not only that frequency, but also the comprehensive nature of that testing. The focus of the MYLUNG program is to continue to iterate and innovate opportunities to expand the testing type and rate for patients that are dealing with their first line of therapy.

Is there any other advice that you can give to other oncologists or researchers on how we can further advance the field?

Keep pushing the needle. I can't stress enough the importance of advancing any of the treatment standards of any diseases is to actually participate in these clinical trials. We really want to focus on enrollment and try to find a research option for every patient who's being considered for standard of care if it's relevant. I would also advise other oncologists to keep asking the questions, because these hypotheses are the important soil for which we can plant the trials of the future. We need engagement by as many of the practitioners as we can to help building that new portfolio of the future.

_Reference:

_{Robert NJ, Nwokeji ED, Espirito JL, et al. Biomarker tissue journey among patients (pts) with untreated metastatic non-small cell lung cancer (mNSCLC) in the U.S. Oncology Network community practices. J Clin Oncol. 2021; 39 (suppl 15: abstr 9004). doi: 10.1200/JCO.2021.39.15_suppl.9004}