9 Facts About Non-Small Cell Lung Cancer
Despite Challenges, Treatments Advance For Small Cell Lung Cancer
As part of its Speaking Out video series, CURE® spoke with Amy C. Moore of Lungevity about advancements in treatments for small cell lung cancer.
Small cell lung cancer, constituting about 15% of all lung cancer diagnoses, has historically presented formidable challenges in treatment. However, recent progress in research offers hope for patients who have received this diagnosis, as Amy C. Moore, vice president of global engagement and patient partnerships for LUNGevity, told CURE® as part of the "Speaking Out" video series.
Moore discussed several clinical trials showcasing significant advancements. Notably, the IMpower133 trial showed a five-year overall survival (how long patients lived following treatment, regardless of disease status) of 12% among patients treated with the immunotherapy Tecentriq (atezolizumab) plus chemotherapy, a substantial improvement compared to the mere 2% survival rate in patients receiving only chemotherapy.
While identifying which patients benefit most from this combined approach remains a challenge, ongoing research aims to pinpoint biomarkers that predict treatment response, Moore said.
Similarly, the CASPIAN study demonstrated promising outcomes by pairing the immunotherapy drug Imfinzi (durvalumab) with platinum-based chemotherapy. This combination exhibited three times more survivors at three years compared to those treated with standalone chemotherapy. These studies underscore the efficacy of combining immunotherapy with traditional chemotherapy, offering survival benefits for patients with extensive-stage SCLC.
Immunotherapy operates by leveraging the body's immune system to target cancer cells, representing a significant paradigm shift in cancer treatment.
Despite these advancements, several hurdles remain, including the relative rarity of SCLC compared to non-small cell lung cancer (NSCLC).
"Despite all the advances we've made in the treatment of non-small cell lung cancer, where we have a number of actionable biomarkers and targeted therapies and immunotherapy that have really opened up the survival and quality of life for those patients, we haven't seen the same gains in patients diagnosed with small cell [lung cancer]," said Moore. "We're trying to understand biologically what's different about small cell. Patients diagnosed tend to be diagnosed at late stages. It's a more aggressive form of the disease, a more aggressive form of lung cancer, so it often responds well initially to chemotherapy but then the tumor, it does what it does, and patients can find that the chemotherapy stops working. And so, we just don't have as many options available for small cell as we do for non-small cell, but it's an area of intense investigation."
Ongoing research explores novel treatment modalities. The DeLLphi-301 study investigated tarlatamab, a bispecific T-cell engager that bridges SCLC cells with T-cells, facilitating targeted cell destruction. Additionally, antibody drug conjugates (ADCs) show promise by selectively delivering drugs to cancer cells, potentially enhancing treatment efficacy.
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American Lung Association, Gateway For Cancer Research Announce Funding Of Innovative Lung Cancer Research
As part of a shared commitment to advance early phase lung cancer clinical trials, Gateway for Cancer Research and the American Lung Association Research Institute continue to expand their co-funding alliance, investing in promising research led by brilliant physicians. Most recently, the organizations together provided $50,000 in grant funding for a trial through the Young Investigator Award (YIA). A program of Conquer Cancer, the American Society of Clinical Oncology Foundation, the YIA provides research funding to physicians who are transitioning from fellowship programs to faculty positions at their respective institutions. Through the YIA, Gateway and the American Lung Association's Accelerator Program funded an early phase lung cancer trial led by Jacob Zaemes, MD, PhD.
A second-year fellow at Georgetown University Medical Center, Dr. Zaemes is one of 91 investigators to have received a YIA at the June 2023 ASCO Annual Meeting. Thanks to additional support from Gateway and the American Lung Association, his trial will investigate the safety and efficacy of an experimental drug for patients with relapsed and refractory extensive-stage small cell lung cancer (SCLC), an aggressive type of lung cancer that typically grows and spreads quickly despite treatment.
The experimental drug, MCG018, has two main components: an antibody which helps the drug seek out and attach specifically to cancer cells, and an active chemotherapy agent which kills the cancer cells. This drug aims to provide a more focused treatment that affects only cancer cells, unlike traditional chemotherapy which also affects non-tumor cells. The focus of the study will be to determine if the drug can shrink patients' cancers. Enrollment for the Phase II, three-year study will include up to 17 participants with patients beginning trial treatment in 2024.
The YIA marks the second clinical trial co-funding endeavor from Gateway and the American Lung Association. The first launched in 2022 and is led by Jeffrey Ward, MD, PhD, a medical oncologist at Washington University School of Medicine. That five-year study centered on integrating a personalized vaccine in combination with an immunotherapy drug into first-line therapy for SCLC.
The partnership capitalizes on Gateway's leadership in exclusively funding Phase I and II clinical trials for all types of cancer. Recognizing the invaluable role these early research efforts play in expanding knowledge on how to safely and effectively treat cancer, the American Lung Association joined forces with Gateway to increase early phase research for lung cancer, the second most common cancer among men and women worldwide.
"Gateway's vision to shape a world in which a cancer diagnosis is no longer feared requires identifying the most promising cancer treatment ideas from passionate physicians and providing the funding to bring those ideas to life," said Delora Senft, Gateway's chief operating officer. "The American Lung Association shares our commitment, and we are honored to partner with them to support Dr. Zaemes."
"Lung cancer is the leading cause of cancer deaths in the U.S., but fortunately, we have seen incredible progress in research into new and better treatments for this disease. SCLC is especially challenging to treat, so we are excited about Dr. Zaemes' research," said Albert Rizzo, MD, Chief Medical Officer for the American Lung Association. "It is critical for the research community to work together to end lung cancer, so we are thankful to advance our work with Gateway for Cancer Research."
This partnership is an initiative of the Accelerator Program, as part of the American Lung Association Research Institute, which launched last year to address the urgent and critical lung health challenges in our country. The Accelerator Program collaborates with government, non-profits and private industry to dramatically accelerate existing research to revolutionize lung health discovery and innovation.
Small Cell Lung Cancer: It's A Time To Be Hopeful
Patients with small cell lung cancer have reasons to be optimistic these days, as one expert explains to CURE.
An expert spoke with CURE about small cell lung cancer and noted that "it's a time for patients with small cell to be hopeful."
It's a time for patients with small cell lung cancer (SCLC) to be hopeful, as Amy C. Moore, vice president of global engagement and patient partnerships for the LUNGevity Foundation said. "There have been various reasons why we haven't seen as many gains in this space," Moore said. "I think it's just a much different beast than non-small cell lung cancer (NSCLC) for a variety of reasons. But we're more hopeful now than we've been in quite some time."
For example, data from the phase 3 IMpower133 trial showed a five-year overall survival (how long patients lived following treatment, regardless of disease status) rate of 12% among patients treated with the immunotherapy Tecentriq (atezolizumab) plus chemotherapy.
"While that doesn't sound like a very high number, for comparison, in patients receiving only chemotherapy, the overall survival is only 2%," Moore noted.
The Food and Drug Administration (FDA) approved Tecentriq plus chemotherapy as a treatment for patients with extensive-stage SCLC in 2019 based on the results of IMpower133, which was followed by the FDA's approval of the immunotherapy Imfinzi (durvalumab) plus chemotherapy for extensive-stage SCLC in 2020 based on findings of the phase 3 CASPIAN trial.
The research continues. The first patients were recently dosed in a phase 1/2 trial of the immunotherapy HPN328 and Tecentriq, while the FDA has also granted a priority review to a biologics license application for the immunotherapy tarlatamab for patients with advanced SCLC.
Moore discussed the science behind these treatments and explained why they represent a sea change for patients with SCLC as part of CURE's "Speaking Out" series.
Q:What should patients with SCLC know about the current advancements in research for treatments?
A: Small cell lung cancer is one of the two main types of lung cancer, accounting for about 15% of all lung cancer diagnoses. And historically, it's been more difficult to treat. For decades, we didn't have a lot of options to offer patients with lung cancer. Chemotherapy was kind of the standard approach to managing that diagnosis. But we've seen a lot of recent progress that offers hope for patients who are diagnosed with small cell lung cancer.
Q: What are some trials that patients should be providing particular attention to and why?
A: There's one called IMpower133, which [was] a study looking at the use of an immunotherapy drug called [Tecentriq] in combination with the platinum-based chemotherapy carboplatin or cisplatin that's typically been used for treating small cell lung cancer along with a [chemotherapy] drug called etoposide. ... So, we're starting to see some gains in survival, a durable survival benefit in some patients with small cell who are receiving that combination of immunotherapy and chemotherapy. One of the challenges with that study is that we can't yet predict who those patients are who are going to derive that benefit.
That's an area of ongoing investigation by researchers: Are there specific biomarkers that may predict who will get the most benefit from the addition of immunotherapy to their treatment regimen?
Another similar study is the CASPIAN study, which evaluated the use of a drug called [Imfinzi] in combination again with platinum-based chemotherapy, compared to patients receiving chemotherapy only. What they found in that study is that there were three times more survivors at three years in the [group of] patients receiving immunotherapy in combination with chemotherapy compared to the patients receiving chemotherapy alone.
In both these studies, IMpower133 and the CASPIAN study, they're looking at the combination of immunotherapy added to traditional chemotherapy. And in both cases, you're seeing a survival benefit and long-term survival in patients.
Going forward, we need to understand and be able to predict who those patients are that may derive that biggest benefit from the addition of immunotherapy, but [it's] still very exciting and a sign of encouragement and, again, it validates the use of immunotherapy combined with chemotherapy in the first-line setting for patients diagnosed with extensive-stage small cell lung cancer.
Q: How does immunotherapy work to help the patient's body deal with cancer?
A: Basically, immunotherapy harnesses the patient's own immune system to go after and target the cancer. People hear about the brakes of the immune system and PD-L1 and PD-1 inhibitors, so there are these checkpoint inhibitors that scientists have learned how to manipulate, and they can basically activate the patient's own immune system to try to go after and target the cancer. And that's the goal here, to tap into the patient's own ability to go after and treat the cancer.
Q: What are some roadblocks to treatment advancements that might exist due to factors such as the relative rarity of SCLC compared to NSCLC?
A: Of the two main types of lung cancer, we have non-small cell lung cancer and we have small cell lung cancer where small cell contributes about 15% of all diagnoses. It has typically been categorized as what we call recalcitrant cancer — that means it's refractory or resistant to treatment.
Despite all the advances we've made in the treatment of non-small cell lung cancer, where we have several actionable biomarkers and targeted therapies and immunotherapy that have really opened up the survival and quality of life for those patients, we haven't seen the same gains in patients diagnosed with small cell.
We're trying to understand biologically what's different about small cell.
Patients tend to be diagnosed at late stages [and] it's a more aggressive form of lung cancer. So, it often responds well initially to chemotherapy, but then the tumor does what it does and patients can find that the chemotherapy [eventually] stops working.
And so, we just don't have as many options available for small cell as we do for non-small cell, but it's an area of intense investigation.
There are some other classes of drugs that are being evaluated to treat it. Another study ... Is the DeLLphi-301 study, which looked at a drug called tarlatamab, which belongs to a new class of [immunotherapy] drugs called bispecific T-cell engagers. Back to this idea of harnessing the patient's own immune system to go after and attack cancer, what bispecific T-cell engagers do is they allow us to bridge the small cell lung cancer cell with a T cell so they can bind to a molecule that is expressed by the small cell lung cancer tumor itself, a molecule in this case called DLL3, as well as a molecule expressed on the surface of the T cell called CD3. By linking those cells together, the T cell can then go in and lance or burst the small cell lung cancer cell.
It's a novel class of drugs harnessing the patient's own T cells to go in and attack and kill the small cell lung cancer. ... This was based on a phase 2 study where the objective response rate (patients who responded partially or completely to treatment) was roughly 40% and we saw median overall survival at 14.3 months.
Some [of the] safety considerations are that in some patients, because you're stimulating the immune system, their immune systems go into overdrive, and [as a result] you can have something called cytokine release syndrome, where your body starts producing too many [proteins known as] cytokines, and you can have some complications from that. Another is that you can get some immune-associated neurotoxicity.
But again, it's a novel class of drug that's using the immune system, and it's something that I think is very promising and that we'll continue to evaluate.
A second class of drugs is antibody-drug conjugates [ADCs]. That's another space where you're using an antibody molecule to … bind a certain molecule, again, expressed on the small cell lung cancer surface. In this case, investigators looked at ADCs that bound to that DLL3 marker on the small cell cancer, and then the antibody brings in a payload of a drug that can go in and selectively, specifically treat the cancer.
We're seeing mixed results on the use of [ADCs], both in the non-small cell lung cancer space as well as the small cell space, but it's an area that's the subject of a lot of research right now, and shows a lot of potential.
It's a time for patients with small cell to be hopeful. There have been various reasons why we haven't seen as many gains in this space. It's just a much different beast than non-small cell lung cancer for a variety of reasons. But we're more hopeful now than we've been in quite some time.
Transcript edited for clarity and conciseness.
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