On June 1st, 2022, LUNGevity Foundation hosted a Facebook Live to discuss our manuscript titled “The 2021 Global Lung Cancer Therapy Landscape” published in the Journal of Thoracic Oncology.
The FB Live discussion included first author, Dr. Dhruba Deb from Columbia University, and Dr. Amy Moore (VP of Global Engagement and Patient Partnerships), and Dr. Upal Basu Roy (Executive Director of Research) from LUNGevity Foundation. The question and answers below are a simplified transcript from the FB Live discussion and provide a high-level overview of why we conducted this analysis and what it means for the lung cancer community.
Why did we conduct this analysis?
We have seen a tremendous amount of progress in the lung cancer space over the past five to 10 years. The goal of this particular project was to reflect upon that progress and discuss what is in the drug development pipeline for the future. As patient advocates, one of the key questions we always think about is, “Are there enough treatment options for patients so that no patient is left behind?” Secondly, “Are those drugs accessible for all patients?” Additionally, LUNGevity Foundation funds research into lung cancer early detection and treatment. We wanted to understand from this analysis if there were any gaps in the lung cancer treatment landscape that we as a foundation want to fund going forward.
How did we use data visualization to showcase a huge amount of data? What were some of the key takeaways?
We used a highly enriched dataset describing several aspects of 707 therapeutic entities. There are several ways to describe and visualize this dataset. The sole reason we opted for a sunburst plot for Figure 1 was to make sure that the patient community found it understandable. The plot also shows therapeutic entities in four different categories (immuno-oncology and non- immuno-oncology assets in NSCLC, and immuno-oncology and non- immuno-oncology assets in SCLC) compared to each other, all at the same time. From this visualization, we found four main takeaway messages. First, we see consistent forward movement in the development pipeline for both NSCLC and SCLC. Second, most of the therapeutic entities are in advanced stages of clinical trials. Third, targeted therapies continue to dominate in the non-immuno-oncology space. And finally, immuno-oncology targets are expanding beyond inhibitors of PD-L1 axis.
Why is this work important for the patient community?
There are multiple reasons this work is important for patients. First and foremost, we just concluded Lung Cancer Hope Month, and this analysis conveys that there's a lot of hope for patients. There are many therapeutic entities in the pipeline that are being developed not only for NSCLC but for SCLC as well. Historically, patients with SCLC have felt left behind, and we haven’t appreciated some of the same forward progress that we've seen in recent years for non-small cell lung cancer. There's a lot of movement and momentum when it comes to research for new drugs, both for NSCLC and SCLC. We're continuing to see a lot of progress for targeted therapies. LUNGevity is also engaged with a number of patient communities at this point, they're defined by their unique biomarkers. So for those patients who are on targeted therapies, they often wonder what's next for me if my current drug stops working? We have a robust pipeline and for patients, there is a lot of hope and promise.
What are some of the key findings related to non-small cell that are captured here?
For patients whose cancers have driver mutations (such as EGFR or ALK), the big question is what’s next when the current treatment stops working. This analysis shows that there are several new drugs being developed for the biomarker-driven NSCLC subsets. The other groups of patients with NSCLC whose tumors do not have driver mutations typically receive some form of immunotherapy alone or in combination with chemotherapy as their first treatment. Even for this group of patients, the “what’s next?” is important because cancer cells can become resistant to immunotherapy. We were thrilled to see that the pipeline for immuno-oncology is also huge. There will definitely be a lot of treatment options for this group of patients in case they have to think of what's next.
Will the lung cancer treatment landscape become more biomarker-driven?
The NSCLC landscape is dominated by targeted therapies. Around 85% of the total NSCLC therapeutic entities are targeted therapies. We have seen that proliferative signaling inhibitors make up the major fraction. As we looked deeper into this area, we noticed the continued advancement and development of inhibitors for oncogenic drivers, such as ALK, BRAF, EGFR even the HER2/ERBB2 family, KRAS, MET, NTRK, RET, and ROS1. So, we will continue to see more targeted therapies in the NSCLC space, including therapeutic entities that target new drivers, such as NRG1. We also anticipate that immuno-oncology will become more biomarker-driven.
What are some key takeaways about clinical trials and clinical research that were revealed through this analysis?
Most of the therapeutic entities we looked at were in either Phase 2 or Phase 3 clinical trials, so they are much further along in terms of clinical development. We didn't really look at early phase clinical trials. We're really seeing an explosion not only of immuno-oncology drugs but also of targeted therapy drugs. That gets into some logistical considerations as we think about just the challenges of accruing enough patients to each of those clinical trials going forward, and some duplication of therapeutic entities. We see a lot of work in the PD-1/PD-L1 space, for example, when it comes to immuno-oncology. As we see more of those clinical trials, it does bear consideration for how we can manage those trials to ensure that we can get enough patients for those trials to meet their endpoints, for example. While it's good that we're seeing so much progress, it does present some realities that we need to think hard about going forward.
What are some of the new approaches for small-cell lung cancer seen in the analysis?
Our analysis revealed some very interesting and promising insights. Keep in mind that traditionally, whether for limited-stage-SCLC or extensive-stage-SCLC, the chemotherapy backbone is a major component of the treatment landscape. For ES-SCLC, the only treatment option that is offered is a chemotherapy-immunotherapy combination. Our analysis reveals that we're expanding the repertoire of targets in SCLC. Targeted therapies, something that we thought about only in the NSCLC space, now we are actually seeing a lot of targeted therapies being tested in SCLC as well. For example, targeted therapies that block the DNA damage response, targeted therapies that block cell division, or targeted therapies that can actually stimulate cell death by blocking proteins such as Bcl2. Conversely, on the immuno-oncology side, we are seeing a lot of progress in two broad buckets: more checkpoint blockade inhibitors such as PD-L1 inhibitors and molecules that stimulate the immune system.
Combination therapies are commonly used in lung cancer treatment. What does our analysis reveal about combination therapies?
Taking the example of the PD-L1 targeted therapeutic entities, our analysis on clinical trials shows most clinical trials are being conducted at multiple sites and using another drug in combination with the PD-L1 blocking agent, such as chemotherapy, targeted therapy, and other immunotherapy entities such as those that target CTLA-4. And then secondly, bispecifics. These are antibodies that are unique: they can target and block two different signals. In our analysis, we have found several examples of these entities that target both the oncogenic, as well as the immune component, such as targeting PD-L1 at one side and TGF-β1 at the other side, or let's say EGFR at one side and CD3 at another side. Another bispecific named amivantamab targets two oncogenic pathways, EGFR and MET. This is very important. Traditionally, patients received either a targeted therapy or an immunotherapy treatment choice, speaking broadly. We hope that these bispecifics targeting multiple components will provide better efficacy and less toxicity for the patients.
What are some of the key takeaways from this analysis for the global lung cancer community?
At LUNGevity, we have two main goals. One is to improve outcomes for people with lung cancer and the other is to improve how they live with lung cancer. There's a lot of promise, but there are some real calls to action within this paper. The first one highlights the explosion of targeted therapies. It really reinforces the work that we do to advocate for patients to get access to comprehensive biomarker testing. That's the first step in ensuring that patients can get matched to the right treatment for them to ensure optimal outcomes. And that's true regardless of where patients are located around the world. The other piece of this is access to these drugs as they're being developed. We want to ensure health equity and a global approach to delivering these drugs because we want all patients, regardless of where they are, to benefit from the advances that we're seeing in the research space. Those are the two key takeaways that we want to make sure that we're getting these advances in these drugs in the hands of the people who need them the most. The final message is we're coming up to ASCO, which is a large convening of people from around the world who are talking about research. We expect to see more updates on many of the drugs that are talked about here, and we're excited to see what comes next, but we appreciate the opportunity to have conducted this analysis and hope it will prove meaningful for all people, providers, and for patients and for the lung cancer community at large.