Lung cancer is one of the most common and deadly types of cancer worldwide, especially for people with squamous non-small cell lung cancer (NSCLC), a subtype that accounts for about 30% of all lung cancer cases. Finding effective treatments for this disease is challenging, as different patients may have different genetic mutations or biomarkers that affect how they respond to different drugs.
To address this challenge, a group of researchers and partners launched the Lung Cancer Master Protocol (Lung-MAP) in 2014, a biomarker-driven master protocol that aims to improve access and outcomes for patients with advanced NSCLC. Lung-MAP is a public-private partnership that includes the National Cancer Institute (NCI), the National Clinical Trials Network (NCTN), SWOG Cancer Research Network, Friends of Cancer Research, the Foundation for the National Institutes of Health, Foundation Medicine, pharmaceutical companies, and lung cancer advocacy organizations.
What is Lung-MAP and how does it work?
Lung-MAP is a unique clinical trial design that allows multiple substudies to be conducted under a shared screening protocol. This means that patients who enrol in Lung-MAP only need to undergo one comprehensive genomic testing using the FoundationOne assay, which can detect hundreds of mutations and biomarkers in their tumor samples. Based on the results of this testing, patients are then assigned to one of the substudies that match their biomarker profile, or to a non-match substudy if they are ineligible for any of the biomarker-driven substudies.
The substudies evaluate different targeted therapies that are designed to inhibit specific pathways or molecules that are involved in tumor growth and survival. For example, some of the substudies tested drugs that target PIK3CA, FGFR, MET, or homologous recombination repair deficiency (HRD) alterations. The non-match substudies evaluated immunotherapies that aim to boost the immune system’s ability to fight cancer cells.
Lung-MAP also allows patients to enrol in multiple substudies after they progress on their initial treatment, giving them more options and opportunities to benefit from new therapies. Additionally, Lung-MAP can adapt to new scientific discoveries and add or remove substudies as needed, making it more flexible and efficient than conventional clinical trials.
What are the benefits of Lung-MAP for underrepresented groups?
One of the goals of Lung-MAP is to improve access and representation of patients who are historically underrepresented in clinical trials, such as older patients, rural patients, socioeconomically deprived patients, and patients with Medicaid or no insurance. These groups often face barriers to participate in clinical trials, such as lack of awareness, transportation difficulties, financial constraints, or eligibility criteria.
A recent analysis published in the journal JCO Precision Oncology compared the sociodemographic characteristics of more than 3,500 patients enrolled in Lung-MAP from 2014 to 2020 with those of more than 2,200 patients enrolled in other SWOG trials for advanced NSCLC. The results showed that Lung-MAP enrolled higher percentages of patients who were older (57.2% versus 46.3%), rural (17.3% versus 14.4%), socioeconomically deprived (42.2% versus 36.7%), or had Medicaid or no insurance (27.6% versus 17.8%) than other SWOG trials.
These findings suggest that Lung-MAP has successfully broadened trial access for some underrepresented groups who may otherwise have limited options for treatment. By including these groups in clinical research, Lung-MAP can help reduce health disparities and improve health equity in lung cancer care.
What are the challenges and limitations of Lung-MAP?
Despite its achievements and advantages, Lung-MAP also faces some challenges and limitations that need to be addressed. For instance, Lung-MAP still underrepresents some groups, such as female (38.6% versus 47.2%), Asian (2.8% versus 5.1%), or Hispanic (2.4% versus 3.8%) patients compared to other SWOG trials. These groups may have different biological or cultural factors that affect their response to treatment or their willingness to participate in clinical trials. Therefore, more efforts are needed to increase the diversity and inclusion of these groups in Lung-MAP and other clinical trials.
Another challenge is the complexity and cost of conducting a master protocol like Lung-MAP, which requires extensive collaboration and coordination among multiple stakeholders, such as researchers, regulators, funders, industry partners, and patient advocates. Lung-MAP also relies on the availability and affordability of genomic testing and targeted therapies, which may vary across different regions and health systems. Moreover, Lung-MAP has to balance the trade-offs between speed and quality, as well as between innovation and standardization, when designing and implementing its substudies.
What are the implications and future directions of Lung-MAP?
Lung-MAP is a pioneering and innovative approach to improve lung cancer treatment for patients with advanced NSCLC, especially for those who are underrepresented in clinical trials. Lung-MAP has demonstrated the feasibility and benefits of using a biomarker-driven master protocol to accelerate the development and evaluation of new therapies, while also increasing the access and representation of diverse patient populations. Lung-MAP has also inspired and influenced other master protocols in oncology and other diseases, such as the NCI-MATCH, GBM AGILE, and I-SPY trials.
However, Lung-MAP also faces some challenges and limitations that need to be overcome to optimize its impact and sustainability. Lung-MAP needs to continue to adapt to the evolving scientific and clinical landscape of lung cancer, as well as to the changing needs and preferences of patients and stakeholders. Lung-MAP also needs to address the barriers and gaps that prevent some groups from participating in clinical trials, such as lack of awareness, education, engagement, or trust. Lung-MAP also needs to collaborate and share data and best practices with other master protocols and research initiatives, to foster learning and improvement across the field.
Lung-MAP is a novel and promising model for advancing lung cancer research and care, but it is not a panacea. Lung-MAP still requires ongoing evaluation and refinement to ensure its quality, efficiency, and equity. Lung-MAP also needs to be complemented by other strategies and interventions that can improve the prevention, diagnosis, treatment, and survivorship of lung cancer for all patients.