Project PRIORITY: Elevating the Patient Voice in EGFR-Positive NSCLC Care

In this interview, Upal Basu Roy, PhD, MPH, LUNGevity, shares findings from his study entitled “Access to Diagnostics and Treatment for People With Metastatic EGFR-Positive NSCLC: Lessons From Project PRIORITY.” He discusses the collaboration between patients and the LUNGevity Foundation to better understand patients’ experiences, and how Project PRIORITY can influence future patient-reported studies for non–small cell lung cancer (NSCLC).

Please introduce yourself by stating your name, title, organization, and relevant professional experience.

Upal Basu Roy, PhD, MPH: Hi everyone. My name is Dr Basu Roy, and I am the executive director of research at LUNGevity Foundation, a lung cancer patient advocacy group. I have been in lung cancer patient advocacy for the past 10 years, prior to which I was a cancer researcher and a public health scientist. At LUNGevity Foundation we've been conducting patient experience research for the past 8 years, and Project PRIORITY is one such project.

Can you tell us a bit about project PRIORITY and what the team's main goals are?

Dr Basu Roy: Project PRIORITY started with three patients who were diagnosed with epidermal growth factor receptor (EGFR)-positive NSCLC and who co-founded the patient group, the EGFR Resistors. The three of them got together to discuss how we can involve patient-reported data and how we can learn more directly from the patient community. They reached out to LUNGevity Foundation to partner on this project.

A key thing about Project PRIORITY is that it was patient founded and patient driven, and it was a great collaboration with LUNGevity Foundation. They brought the patient experience and we brought the methodological expertise in terms of the goals of the project. The key goal of the project was to give patients and caregivers from the EGFR community a voice about risk factors, types of treatments patients were receiving, the symptoms of the disease and different side effects associated with disease, and how to manage the disease. The goal of this project was to understand needs of the EGFR-positive NSCLC community and, equally important, to identify areas of improvement in diagnosis and treatment.

Can you give briefly summarize your study and its key takeaways?

Dr Basu Roy: Project PRIORITY was a survey-based study that relied on patient reporting. We had questions about how patients were diagnosed, what types of treatments they received in the first-line setting, what other treatments they had received, if their disease progressed, and what other types of support they had during their cancer journey.

There were 3 important findings. First of all, when we asked members of the EGFR-positive community whether they had received any kind of next- generation sequencing (NGS), we learned that only about half of the respondents had received some type of NGS-based testing, whether it was tissue or liquid. That means the majority of the population was being diagnosed with single analyte testing. This is critical to keep in mind because NGS testing not only identifies specific types of EGFR mutations, but it also helps identify other co-occurring mutations which are equally important in the treatment of EGFR positive lung cancer. Keep in mind that the study was done in 2019, so NGS was not as mainstream. However, even within the US, we found that patients did not receive NGS testing, which was surprising to us.

The second key finding is about the treatment journey of the patients. In 2018, the new EGFR treatment osimertinib was approved in the US and in Europe, and we were expecting that it would be more commonly used in our sample, but that is not what we found, especially in patients who were living outside the US. Osimertinib was not the most commonly prescribed tyrosine kinase inhibitor (TKI), which shows that during the time of the study, patients did not have access to the best standard of care.

The third finding that I want to highlight—which is probably the most important but the most underexplained and under described in literature—is the use of palliative care in the treatment of lung cancer. Because our sample size was mostly patients with metastatic disease, we expected more use of palliative care, but only about 13% of our sample reported the use of palliative care. This was even lower outside the US, where only about 4% of our respondents told us that they had access to palliative care. This is important is because there is good data available showing that early integration of palliative care in the treatment of advanced (NSCLC) leads to better outcomes. There is this myth in the community that suggests that palliative care is primarily for either patients with early-stage disease or patients who are nearing their end of life. Palliative care is equally as important when a patient is starting their first treatment because it helps with symptom control as well as side effect management.

Those are the 3 key points, access to diagnostics, access to treatment, and access to palliative care.

The study highlights how TKIs have been practice-changing for EGFR-mutated NSCLC. Based on the survey findings, how would you characterize the real-world impact of TKIs on patients’ quality of life and long-term treatment experiences?

Dr Basu Roy: All of the data that we have about how patients are feeling and functioning on TKIs come from clinical trials. Our study was a real-world study where we asked patients outside of a clinical trial setting how they were doing on different drugs, including some of the newer generation TKIs such as osimertinib. We looked at a subset of our sample, which were patients who were on first-line treatment and specifically on osimertinib. We asked them about the most common side effects they were experiencing. A high percentage of patients in our patient community reported mild fatigue (64%), muscle cramps (42%), and diarrhea (34%) as their mild side effects.

I bring this up because very often when we are looking at clinical trials, we tend to focus on grades 3 and 4 side effects, which from a clinician perspective are the most important because they need to be managed. But from a patient perspective, mild side effects, or grade 1 and 2 side effects, are equally important because they can impede activities of daily living. They basically stop patients from living their life to the fullest.

When we compared the rate of side effects in our population vs the FLAURA2 trial, the main trial that led to the approval of osimertinib, patients in our sample reported higher rates of some of these side effects. This is with the caveat that we are making a comparison between a real-world sample and a clinical trial sample, which is difficult to do because of the way of measurement. But even if we took this information directionally, it's important to keep in mind that TKIs have impacted survival, but quality of life is something that still needs to be discussed and considered when you're making treatment decisions.

The study identifies disparities in access to next-generation sequencing and newer treatments like osimertinib, particularly based on residency. What factors do you believe contribute most to these disparities, and what steps could be taken to address them?

Dr Basu Roy: We see disparities in access to both advanced diagnostics and treatments within the US, but these disparities are more amplified in other parts of the world. These disparities are, in my mind, exacerbated in other parts of the world because of different barriers at different levels. For example, at the infrastructure level, many low- and middle-income countries, especially countries in Asia where you have a high prevalence of cancers with EGFR mutation, may lack the infrastructure to do advanced diagnostics. As a result, they rely on simple laboratory facilities that can only do single testing. In addition, often in low- and middle-income countries, prioritization of resources is a critical factor and decision and policy makers are often not aware of the value proposition of some of these advanced diagnostics and these new drugs. There are also provider-level barriers. Providers may feel that they're not able to offer these diagnostics and treatments to their patients, and therefore they may not remove adequate tissue for sampling. They also may not be prescribing some of these TKIs.

So, there are barriers at the infrastructure level, the policy level, the government level, and at the provider level. Some of the easy ways to start advocating for better access is to continue to educate stakeholders and decision makers about the value proposition of these advanced diagnostics and advanced therapeutics. When I say therapeutics, another thing to keep in mind is if we look at the World Health Organization (WHO) model list of essential medicines, which is supposed to be the blueprint that all countries around the world should be using in terms of stocking up medicines, a lot of the new cancer treatments are not listed in the WHO model list of essential medicines. Adding them is an easy fix to introducing some of these new cancer medicines so governments and stakeholders can start taking notice of them.

Your research underscores the need for further exploration of patient experiences. What do you see as the next steps in improving both patient-reported research and the overall treatment landscape for people living with EGFR-m NSCLC?

Dr Basu Roy: The need to integrate patient-reported outcomes (PROs) and patient-reported quality-of-life measures in clinical trials is more important than ever before. In this era of targeted therapeutics, we work on the assumption that a lot of these newer-generation drugs do not impact quality of life. However, as our study revealed, they have a very tangible impact on the quality of life of patients. So, it's important to start integrating more and more PRO measures in clinical trials. Typically, when we think of PRO measures, we are thinking of phase 3 trials. But it's equally important to start integrating some of these PRO data collections in phase 1 trials when a drug is being tested on a patient for the first time.

When you're looking for safety and efficacy signals, part of the safety signals should be looking at patient tolerability through some of these PRO measures. The other piece I would add, which is sort of on the other spectrum of clinical trials, is real-world data collection. Our study revealed that collecting patient-reported data from a real-world sample is incredibly helpful. So, I recommend that we start collecting PRO data from real-world patient samples as well, because this type of data would help clinicians have more fruitful discussions with their patients when they're recommending treatment options.

Now, in terms of further research needs in the overall treatment landscape for people living with EGFR-positive lung cancer, it's important to acknowledge that we have come a long way in treating this type of cancer since the first mutations were discovered in lung cancer in 2004—definitely a reason to celebrate. But we still have a long way to go. Since we did Project PRIORITY when osimertinib was the standard of care for first-line treatment, 2 new additional treatment options have been approved in the US for the treatment of EGFR-positive lung cancer. One is a combination of osimertinib with chemotherapy, which comes from the FLAURA2 trial. The other one is the combination of 2 drugs, amivantamab and lazertinib, which comes from the MARIPOSA trial. Let's unpack these two for a little bit. Now, in the FLAURA2 trial, when people receive a combination of chemotherapy and osimertinib, 57% of that population remains cancer-free after 24 months. So, 43% are not cancer-free after 24 months. Now, when we look at the MARIPOSA regimen, which is looking at amivatanab and lazertinib, again, 48% are cancer-free at 24 months, so that means 52% of patients are not cancer-free.

Despite these advances, we still need more because we need newer therapies that patients can continue to benefit from. In my lifetime, I hope we can have drugs that offer 80% to 90% progression-free survival in 5 years. We are seeing that in some of the other oncogene-driven lung cancers, and I wish the same for EGFR. The last thing I would add is it's not just about drugs that increase overall survival and the length of life. It's also about drugs that increase the quality of life. So, it's not just quantity, but quality of life.