EACH YEAR, TENS OF THOUSANDS OF PEOPLE are diagnosed with small cell lung cancer (SCLC). However, this disease remains poorly understood compared to non-small cell lung cancer (NSCLC), a more common form of lung cancer.
The GO2 Foundation for Lung Cancer is a nonprofit that aims to improve the lives of people at risk for, or diagnosed with, lung cancer. In May, the organization launched an initiative focusing on SCLC, studying best practices based on the work of professionals who are engaged with communities where SCLC is prevalent and learning directly from patients and their caregivers. Cancer Today spoke with Christine Lovly, a medical oncologist and researcher at Vanderbilt University Medical Center in Nashville, Tennessee, and the chair of the GO2 Foundation’s Scientific Leadership Board, about the program and future prospects for the treatment of SCLC.
CT: What is small cell lung cancer, and how is it different from non-small cell lung cancer?
LOVLY: There are more than 235,000 cases of lung cancer in the U.S. every year. About 85% of those cases are the more common type, which most people are familiar with: NSCLC. The other 10-15% of cases are SCLC. That sounds like a small percentage, but it represents tens of thousands of patients, so this is not an uncommon type of lung cancer.
The names come from how the tumors look under the microscope. In SCLC, the tumor cells look small. Another difference is where the tumors originate. We have many different types of cells in the lungs, and these two [types of] tumors have completely different founder cells. While NSCLC is associated with multiple different founder cells, including neuroendocrine, glandular and squamous, SCLC always comes from neuroendocrine cells.
CT: Tell me about the GO2 Foundation’s new initiative.
LOVLY: The GO2 Foundation will be working with our network of community centers of excellence—850 community hospitals that meet rigorous criteria for quality of care—to identify the needs of patients with SCLC. The goal is to really try to understand and address knowledge gaps, not just within how we treat different types of cancer but also within the resources we offer patients to help them feel supported throughout their course of treatment.
We want to know, what are the needs of patients with small cell lung cancer? What are providers struggling with to actually help patients? What issues do patients articulate?
CT: What is the current standard of treatment for SCLC?
LOVLY: In the 1980s, the U.S. Food and Drug Administration approved what we still consider our standard best care for patients with SCLC: platinum-based chemotherapy. Many, many clinical trials have taken place since then, but we saw very little improvement in outcomes until 2019, when the first immunotherapy agent was approved for SCLC. It was the first change in therapy in about 30 years. That’s impactful.
CT: How does immunotherapy change outcomes for patients?
LOVLY: Here’s the challenge: We’ve consistently seen that adding immunotherapy to platinum-based chemotherapy improves overall survival, but only by months. It’s wonderful to have an advance. That’s fantastic. But I think we could all agree that we have a lot of work to do, that we would like the improvement in survival to be much longer than what we’re actually observing.
CT: Patients with NSCLC sometimes benefit from targeted therapies. Are any targeted drugs available to patients with SCLC?
LOVLY: Right now, in NSCLC, we have this explosion of targeted therapy options. We have this long list of mutations that can be tested for and targeted. Despite an increasing number of biomarkers or drug targets for NSCLC, that similar paradigm—that growth of targets and biomarkers—has not occurred in SCLC to date. Right now, a lot of lab research is trying to understand how we subtype SCLC to actually be able to deliver precision personalized care. But we haven’t gotten there yet.
CT: Why is that?
LOVLY: Part of it is the way the tumors are wired. NSCLC tumors are more likely to have oncogenes, a change in the tumor that accelerates its growth. SCLC tumors are more likely to have mutations that turn off tumor suppressors, which are genes we need to slow tumor growth. On a molecular level, it’s easier for us to use drugs to turn something off once it’s on—an oncogene, for example—than to turn a gene like a tumor suppressor back on. Fortunately, right now, there are a lot of smart people trying to solve this problem. Practically speaking, it’s a little bit harder to get tumor samples from patients with SCLC, for a variety of reasons. It’s not as simple to get your hands on an SCLC tumor to study in a research lab.
CT: Are there any new treatments on the horizon?
LOVLY: Yes, lots. Different types of immunotherapy are in clinical trials that are trying to understand what other immune system targets we can use for patients with SCLC. One target that’s really making a splash right now is called TIGIT, a protein expressed on some immune cells. Other targets include PARP proteins, which lead to defects in DNA repair. Recently, we’ve heard a lot about PARP inhibitors for breast cancer, but they could potentially work in SCLC as well.
There’s really a huge push from a clinical perspective to bring precision into the care of patients with SCLC. So I feel very hopeful and enthusiastic that we’ll have new therapies in the not-too-distant future.
This interview has been edited and condensed for clarity.
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September 21, 2021