MYLUNG Study Explores Molecularly Informed Lung Cancer Treatment

Robert Coleman, MD

Therapies targeting oncogenesis and the tumor microenvironment are increasingly replacing chemotherapies as first-line treatments for non–small cell lung cancer (NSCLC).¹ However, in real-world practice, barriers continue to exist for the uptake and use of comprehensive biomarker testing. Whether it is because of long turnaround time frames for molecular testing, payer concerns and a lack of coverage, or another factor, many patients are not receiving the molecular testing they need to initiate targeted therapy early in their cancer care journey. To fulfill the promise of precision medicine for patients with NSCLC, a better understanding of the barriers, challenges, risks, and opportunities around molecular-ly guided therapies for lung cancer is needed.

Sarah Alwardt, PhD

Recognizing that a large-scale study of the data is needed for deeper insight into targeted therapy adoption, we have formed the MYLUNG consortium to conduct a broad, national, real-world evidence (RWE) study of more than 12,000 patients with NSCLC over a 5-year period. MYLUNG—or Molecularly Informed Lung Cancer Treatment in a Community Cancer Network: A Pragmatic Consortium—will generate real-world practice patterns across The US Oncology Network (The Network) with active surveillance throughout the patient journey. The overall objective of this programmatic study is to identify and proactively address barriers to targeted treatments so patients can obtain necessary molecular testing at the point of diagnosis and receive the right treatment at the right time in their preferred setting of care.

A Unique Collaboration

The MYLUNG consortium brings together providers and researchers in The Network, US Oncology Research, and Ontada (all supported by McKesson Corporation), biopharmaceutical manufacturers, and patient advocacy groups in a joint effort to advance precision medicine for lung cancer. It marks a unique level of collaboration among diverse organizations and stakeholders, all working together across the spectrum of NSCLC drug development, therapy, and care.

Supporting more than 480 independent, community treatment center locations across the United States, The Network is poised to address the issues surrounding targeted therapy uptake and use; approximately 55% of newly diagnosed patients are seen in the community setting, and many patients prefer to receive cancer care closest to home.² MYLUNG highlights McKesson’s ability to integrate a continuous, virtual cycle with feedback loops between the RWE research team and The Network sites of care to quickly integrate best practices across The Network while adaptively responding to the constantly changing landscape of oncology discovery for both diagnostics and treatment.

Meanwhile, biopharmaceutical companies, patient advocacy groups, health care policymakers, payers, and other stakeholders will deepen their understanding of the barriers to care for patients with targetable mutations that may benefit from receiving precision medicine therapies as first-line treatments. With an unprecedented level of engagement among consortium participants, the MYLUNG program will be one of the first broad, prospective, postmarketed research endeavors in lung cancer.

An Increasingly Complex Landscape

Eighty-four percent of lung cancers are NSCLC, affecting approximately 228,000 patients per year in the US.³Among the 3 main classes of treatments—chemotherapy, immunotherapy, and targeted therapy—the latter category is growing at an exponential rate. Every year, a new crop of targeted therapies is approved for ever-smaller populations of molecularly annotated patients. What was once recognized as 2 NSCLC diseases, squamous cancer and adenocarcinoma, is now about 10 different disease states. We are in an adaptable situation as new mutation discoveries lead to increasingly subdivided tumor types, for which novel therapies are now available.

The FDA has approved several dozen targeted therapies and combinations for NSCLC (eg, ceritinib [Zykadia], bevacizumab [Avastin], osimertinib [Tagrisso], crizotinib [Xalkori], dabrafenib [Tafinlar], pralsetinib [Gavreto], and others). A tremendous amount of bio-pharmaceutical development is ongoing in NSCLC, and the care journey is growing in complexity as providers must navigate an increasingly nuanced world of precision medicine for their patients.

A robust pipeline of double-blind, randomized controlled trials (RCTs) is bringing these new targeted therapies to market, powering a transformation in lung cancer care. Conducted on a specific population of patients who meet eligibility criteria, RCTs produce data that excel at isolating the efficacy and benefit of a specific intervention. However, when a targeted therapy moves into the real world with a heterogeneous patient population, the data often break down because most patients diverge from the trial’s eligibility criteria. The extrapolation of results in RCTs is often very different from patients’ experience with these therapies in the real world.

Although RCTs remain the gold standard in biopharma research, it is crucial to collect RWE through programmatic studies such as MYLUNG, which will interpret the data and generate evidence from thousands of diverse patients. Notably, the purpose of MYLUNG is not to address the comparative effectiveness of different therapies that target the same mutation. Rather, MYLUNG will examine the obstacles to obtaining molecular testing and the decision-making process and timeline that lead a physician to select a treatment for their patient, whether it is chemotherapy, immunotherapy, or targeted therapy.

One such challenge is the molecular-testing timeline, as it can take from 2 to 5 weeks to take a biopsy, send tissue to the lab, and await results and interpretation—always with a risk that a specimen’s quantity or quality will be deemed insufficient or that the data are uninterpretable. Such instances may limit a clinician’s ability to convey information to the patient in a timely way. Oncology practices may implement caregiving interventions—such as using blood assays, tissue navigators, genetic counselors, or process plans—to address hurdles to testing and the uptake and use of targeted therapies. However, practices have little data about such interventions. MYLUNG will change that, drawing on RWE to provide a framework of best practices for providers, based on the heterogeneity of their baseline practice experience.

A Programmatic Study With 3 Protocols

MYLUNG will consist of 3 protocols, and each will provide value over the 5-year study (FIGURE). In protocol 1, the study examines data in structured fields of the electronic health record to discover trends such as the rate of testing, tests selected, and other practice patterns, and it lays the groundwork for the next 2 study protocols. Protocol 2 will observe multiple factors and events that determine which treatment will be utilized as a patient’s first-line treatment. Protocol 3 will connect the dots, enabling prospective, operational interventions—such as choosing blood-based assays over biopsies; utilizing a tissue navigator or genetic counselor; or developing a process plan—to address barriers. The end goal is to improve the rate of appropriate molecular testing and the subsequent assignment of indicated targeted therapies.

MYLUNG’s Real-World Implications

In addition to the large size and scope of the study, the innovative potential of MYLUNG lies in its pragmatic approach to finding ways that providers can help patients with lung cancer on a practice level. The Network touches a broad spectrum of diverse patient populations, disease presentations, and needs. Innovation n these areas tends to be slow because interventions are often undertaken within a smaller ecosystem, eg, at a single institution. The sheer scale and diverse ecosystem of MYLUNG will allow it to uncover the most effective interventions that can be broadly implemented and then quickly put into practice. Moreover, beyond helping us answer today’s precision medicine questions, the rich data sets from these studies may help us answer the questions of tomorrow as well.

The benefits of MYLUNG extend to patients, providers, and all manner of stakeholders in lung cancer care. Patients and their advocates want to know that they are receiving the best treatment options available to them in a timely manner. Providers must navigate a landscape of cancer care that grows more complex daily, with novel therapies rapidly coming to market. Biopharmaceutical manufacturers are tasked with developing the targeted medications so oncologists can get the right medicine to the right patient, at the right time. Payers need a better understanding of targeted therapies to determine their cost coverage. And policymakers are tasked with comprehending the potential policy implications of the fast-changing science.

MYLUNG has the potential to significantly impact the way patients with NSCLC are cared for in this dynamic new oncology landscape. Mining a wealth of RWE from each of the 3 protocols, the study investigators will be able to recommend customized approaches and a clear methodology of best practices for providers. The hope is that MYLUNG will positively impact the uptake and use of targeted therapies as first-line treatments where clinically appropriate and, ultimately, lead to improved outcomes for patients with lung cancer.

_REFERENCES:

_{1. Yuan M, Huang LL, Chen JH, Wu J, Xu Q. The emerging treatment land-scape of targeted therapy in non-small-cell lung cancer. Signal Transduct Target Ther. 2019;4:61. doi:10.1038/s41392-019-0099-9}

_{2. Fact sheet: what is community oncology? Community Oncology Alliance. 2017. Accessed November 17, 2020. https://bit.ly/37Z4hy5}

_{3. Key statistics for lung cancer. American Cancer Society. Updated January 12, 2021. Accessed January 13, 2021. https://bit.ly/34SIBSc}