New findings from the COAST trial led by researchers at Yale Cancer Center show that adding oleclumab or monalizumab to durvalumab improved progression-free survival for patients with locally advanced non-small cell lung cancer (NSCLC). The findings were presented this month at the annual meeting of the European Society for Medical Oncology (ESMO).
Roy S. Herbst, MD, PhD, Chief of Medical Oncology at Yale Cancer Center and a member of LCRF’s Scientific Advisory Board, is lead author of the study.
LCRF Scientific Advisory Board member Trudy G. Oliver, PhD, received the Heine H. Hansen Lectureship Award for Small Cell Lung Cancer during the International Association for the Study of Lung Cancer’s (IASLC) 2021 World Conference on Lung Cancer last week. The lectureship award recognize clinicians and researchers who made significant contributions to the fight against lung cancer and represent many major categories of lung cancer research, from tumor staging to tobacco control and smoking cessation.
Dr. Oliver was recognized for her work in pharmacology and cancer research. She is an associate professor in the Department of Oncological Sciences at the University of Utah and a Huntsman Cancer Institute (HCI) Endowed Chair in Cancer Research. She currently co-leads the Cell Response and Regulation (CRR) program and the Lung Cancer Center at HCI.
She has received many awards, including the LCRF’s William C. Rippe Award for Distinguished Research in Lung Cancer.
Dr. Oliver’s research is devoted to understanding mechanisms of lung cancer biology with the goal of identifying noval therapeutic targets to improve patient outcomes. Her laboratory has developed multiple, novel mouse models of squamous and small cell lung cancer (SCLC). Using these systems, her lab discovered that the MYC oncogene drives unique molecular subtypes of SCLC, and that SCLC subtypes demonstrate plasticity in mouse and human tumors. Her work has identified multiple therapeutic vulnerabilities for molecular subsets of SCLC, including the observation that SCLC subtypes are metabolocally distinct with MYC-high SCLC uniquely dependent on arginine.
LCRF Scientific Advisory Board member David Carbone, MD, PhD, is the 2021 recipient of the Paul A. Bunn, Jr. Scientific Award. The award was presented at the International Association for the Study of Lung Cancer’s (IASLC) 2021 World Conference on Lung Cancer last week.
Dr. Carbone is professor of Internal Medicine and director of the James Thoracic Oncology Center at The Ohio State University Comprehensive Cancer Center and Solove Research Institute & Professor of Medicine, The Ohio State University. He holds the Barbara J. Bonner Chair in Lung Research.
His recent research directions include development of molecular biomarkers to guide patient treatment, and molecular profiling of lung cancers and preneoplasias to guide the development of novel therapeutics, especially using mass spectrometry-based proteomics. He has more than 200 peer-reviewed publications, books, and review articles, has served on several NCI grant review panels (including the clinical program project parent committee), and has had continuous funding from the National Cancer Institute (NCI) since early in his career. He served on the Board of Scientific Counselors for the NCI, and currently is Chair of the Lung Biology subcommittee for the Eastern Cooperative Oncology Group and Past President of the IASLC.
The Paul A. Bunn, Jr. Scientific Award recognizes an IASLC scientist for a lifetime achievement of scientific contributions to thoracic cancer research. Dr. Paul Bunn’s studies set worldwide standards for the treatment of lung cancer and identified issues of natural history and biomarkers of prognosis and therapy selection. Initially named the Scientific Award, the IASLC renamed the award in honor of Dr. Bunn after he served as the society’s executive director and CEO for 10 years.
The FDA has approved mobocertinib for the treatment of adult patients with locally advanced or metastatic non–small cell lung cancer with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Mobocertinib is the first and only oral therapy specifically designed to target EGFR exon 20 insertions.
FDA approves first targeted therapy for KRAS+ NSCLC
Posted June 1, 2021
The FDA approved Lumakras™ (sotorasib) as the first treatment for non-small cell lung cancer (NSCLC) patients whose tumors have the KRAS G12C genetic mutation and who have received at least one prior systemic therapy. This is the first approved targeted therapy for tumors with any KRAS mutation, which accounts for approximately 25% of mutations in NSCLC.
Rybrevant approved for NSCLC with EGFR Exon 20 insertion mutations
Posted May 27, 2021
The FDA has approved Rybrevant (amivantamab-vmjw) for adults with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
The Guardant360 CDx (Guardant Health Inc.) liquid biopsy test was also approved as a companion diagnostic for use with Rybrevant.
“For the first time, patients with non-small cell lung cancer with EGFR exon 20 insertion mutations will have a targeted treatment option,” said Julia Beaver, M.D., chief of medical oncology in the FDA’s Oncology Center of Excellence and acting deputy director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.
FDA grants fast track status for targeted treatment poziotinib
Posted March 15, 2021
The FDA has granted fast track status for the targeted treatment poziotinib, which is used to treat patients with non-small cell lung cancer (NSCLC) HER2 exon 20 mutations. Fast track is a process intended to accelerate the review of drugs to treat serious conditions and fill an unmet medical need. This new status for poziotinib is welcome news as no FDA approved targeted treatments currently exist for those with the specific HER2 exon 20 mutation.
Research shows brigatinib provides improved health outcomes
Posted March 9, 2021
Almost a year ago, the FDA approved brigatinib (Alunbrig®) for the first-line of treatment of patients with ALK+ metastatic non-small cell lung cancer (NSCLC). Since then, research has continued to provide evidence that brigatinib has consistent superiority in progression-free survival (PFS) compared to the targeted treatment crizotinib (Xalkori®).
Lorlatinib (Lorbrena®) is a targeted treatment that can now be used for metastatic NSCLC patients with ALK-positive tumors in the first-line setting. Prior to this approval, lorlatinib was only approved for use in the second- or third-line setting. The FDA also approved the treatment Ventana ALK (D5F3) CDx Assay as a companion treatment for those using lorlatinib.
Two promising KRAS inhibitors soon to be FDA approved
Posted February 26, 2021
The KRAS G12C mutation leads to a specific type of lung cancer, in individuals who are likely to have been smokers and likely to respond to immunotherapy. Currently, we have several KRASG12C inhibitors that are under clinical development and may reveal an effective targeted treatments for KRAS G12C patients. Sotorasib (AMG 510) and adagrasib (MRTX849) have shown be to effective and researchers believe that these two treatments are very likely to be approved by the FDA within a year as a second-line treatment. This is positive news that will benefit many KRAS patients through their treatment journey.
Yet another immunotherapy is now approved for non- small cell lung cancer (NSCLC) patients! Libtayo® (also known as cemiplimab-rwlc) is an immunotherapy drug that can be used in the first-line setting for NSCLC patients who are not otherwise eligible for surgery or chemoradiation treatment for their diagnosis. NSCLC patients must exhibit high PD-L1 expression with no presence of the EGFR, ALK, or ROS1 aberrations, to be eligible for this new treatment approval.
FDA approves Cosela to reduce bone marrow suppression in SCLC patients
Posted February 16, 2021
The FDA has granted approval to the first-in-class agent trilaciclib (Cosela™) for the treatment of patients with extensive-stage small cell lung cancer (SCLC) to reduce chemotherapy-induced bone marrow suppression.
“For patients with extensive-stage small cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” said Albert Deisseroth, MD, PhD, supervisory medical officer in the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research. The approval “will give patients a treatment option that can reduce the occurrence of a common, harmful side effect of chemotherapy.”
FDA approves Tepmetko for MET exon 14 NSCLC patients
Posted February 4, 2021
On February 3, 2021, the Food and Drug Administration (FDA) granted accelerated approval for tepotinib (Tepmetko®) for the treatment of metastatic non-small cell lung cancer (NSCLC) patients who have the MET exon 14 skipping alterations. This is the second targeted treatment now available for this specific patient group. The FDA approval was based off the VISION trial showing overall response rate was sustained for a median of 10-11 months.
Trial fails to show benefit to combining EGFR tyrosine kinase inhibitor and anti-VEGF agent
Posted February 3, 2021
In a new clinical trial performed by JAMA Oncology, osimertinib (Tagrisso®) plus bevacizumab (Avastin®) failed to demonstrate prolongation of progression-free survival (PFS) compared with osimertinib alone in patients with non-small cell lung cancer (NSCLC). Several other studies are still ongoing and will be looked upon with interest. Additionally, a phase 3 trial of osimertinib with or without bevacizumab is being conducted and can deliver more insight about this treatment.
FDA grants priority review for lorlatinab as first line treatment for ALK+ NSCLC
Posted February 2, 2021
The FDA has granted a priority review of the supplemental new drug application for the third-generation ALK inhibitor lorlatinib (Lorbrena®) as a first-line treatment for patients with ALK-positive metastatic non–small cell lung cancer (NSCLC). This advancement can speed up availability of the potentially life-changing medicine lorlatinib. The goal date for the completion of the review has been set by the FDA for April 2021.
FDA grants breakthrough therapy designation to new immunotherapy drug
Posted January 11, 2021
The FDA has granted a breakthrough therapy designation to a promising new immunotherapy drug called tiragolumab that can be used in combination with atezolizumab (Tecentriq®) as a first-line therapy for metastatic non-small cell lung cancer (NSCLC) patients with high PD-L1 expression. NSCLC patients must not have the EGFR or ALK genomic tumor irregularities present.
This breakthrough therapy designation will accelerate the progress of the CITYSCAPE clinical trial to focus event more on the benefits of tiragolumab as a possible chemotherapy-free combination treatment in earlier stages of cancer.
FDA approves Tagrisso as first adjuvant therapy for earlier stage NSCLC with certain EGFR mutations
Posted January 4, 2021
On December 18, 2020 the FDA approved osimertinib (Tagrisso®) as the first adjuvant therapy that can be used in NSCLC Stage IB-IIIA patients positive for either EGFR exon 19 or exon 21 L858R genetic mutations. Patients must first have undergone resection, or in other words had their tumor removed with surgery, before receiving Tagrisso.
The most exciting part about this approval is that Tagrisso can now be used to treat NSCLC patients in earlier stages as well as late stage. This provides the potential for an earlier and hopefully more curative therapy, which is great news for the nearly 20% of all lung cancer patients who have the EGFR mutation.
FDA grants sotorasib breakthrough therapy designation
Posted December 9, 2020
As of December 8, 2020, the FDA has granted a breakthrough therapy designation for a drug called sotorasib for the treatment of patients living with non-small cell lung cancer (NSCLC) containing the KRAS G12C mutation. This treatment may be used on NSCLC patients after they are confirmed to have the KRAS G12C mutation through the use of an FDA-approved diagnostic test and following at least one other systemic therapy.
The KRAS genetic mutation is the most commonly occurring mutation in adenocarcinoma NSCLC. Furthermore, the KRAS G12C mutation affects roughly 13% of all adenocarcinoma NSCLC patients. In the United States alone, 25,000 NSCLC patients will be diagnosed with this specific mutation every year.
This breakthrough therapy designation for sotorasib brings the lung cancer community closer to finding the very first targeted therapy that can be used to treat this commonly occurring genetic mutation.
The Food and Drug Administration approved “cobas EGFR mutation test v2” to identify NSCLC patients eligible for any of the EGFR inhibitor therapies, including those used to treat EGFR exon 19 and L858R deletions, as well as any EGFR therapies to come in the future.
The Food and Drug Administration granted priority review to cemiplimab-rwlc (Libtayo®) for treatment of certain patients with non-small cell lung cancer.
The designation applies to use as first-line therapy for locally advanced or metastatic NSCLC with 50% or greater PD-L1 expression.
On October 23, the Food and Drug Administration approved the next-generation sequencing (NGS)-based FoundationOne CDx test as a companion diagnostic to help identify NTRK+ solid tumor patients eligible for larotrectinib.
FDA grants expedited review for Tagrisso® in early-stage lung cancer
Posted October 21, 2020
The Food and Drug Administration has granted its Priority Review designation for AstraZeneca’s Tagrisso® in certain patients with early-stage lung cancer.
These faster reviews, which take six months instead of the standard 10-month timeframe, are reserved for medicines that demonstrate significant improvements in efficacy or safety for serious diseases.
FDA approves drug for patients with NSCLC RET mutation
Posted September 8, 2020
On September 4, the Food and Drug Administration granted accelerated approval of Gavreto™ (pralsetinib) for people with metastatic non-small-cell lung cancer (NSCLC) with the RET mutation.
Gavreto™ inhibits a receptor tyrosine kinase known as RET, which plays a role in cell proliferation. RET gene mutations or fusions can drive cancer growth, and about 1-2% of NSCLC patients are thought to be affected.
This is the second drug approved for patients whose cancers harbor RET mutations. This approval provides oncologists and patients with an additional option for treatment.
FDA grants priority review to tepotinib for NSCLC patients with MET
Posted August 27, 2020
The Food and Drug Administration has given priority review to tepotinib, a soon-to-be targeted therapy for NSCLC patients with the MET exon 14 mutation.
This new drug will be in addition to Tabrecta™, which was previously approved for MET exon 14.
FDA approves first liquid biopsy with NGS technology for EGFR
Posted August 7, 2020
On August 7, the U.S. Food and Drug Administration approved the Guardant360 CDx assay liquid – or blood – biopsy. This biomarker test uses next-generation sequencing (NGS) technology to identify patients with the epidermal growth factor receptor (EGFR) gene in a deadly form of metastatic non-small cell lung cancer (NSCLC). This is the first approval to combine two technologies — NGS and liquid biopsy — in one diagnostic test in order to guide treatment decisions.
Typically, biomarker testing involves a tissue sample from the primary tumor. This biomarker testing will use blood instead, while still utilizing the NGS biomarker testing normally done on tissue samples.
Reina Honts named chair, Scott Morris joins foundation’s board
NEW YORK, NY (September 7, 2021) – The Lung Cancer Research Foundation (LCRF) is pleased to announce its newest board chair, Reina Honts, and welcome Scott Morris to its Board of Directors. Dr. Brendon Stiles, who had served as the board’s chair since 2017, has graciously agreed to take on the role of board vice chair and continue in his role as vice chair of LCRF’s Scientific Advisory Board.
Reina Honts
Reina Honts joined the LCRF Board of Directors in November 2018 and served as its secretary prior to being named chair.
Due to her own mother’s death to lung cancer at the relatively young age of 53, she requested a baseline CT scan when she turned 50 in the spring of 2018. Since she had no symptoms and did not smoke, she was surprised when the CT scan revealed a tumor in her lung. She underwent a lobectomy and is now cancer free. It’s likely that early detection changed the outcome of her lung diagnosis, and Ms. Honts shares her experience to help others.
Ms. Honts is a fashion industry executive with 29 years’ experience overseeing design, merchandising and production teams for fashion companies, such as Gap, Cole Haan, Ann Taylor and Bergdorf Goodman.
She is also actively involved in several charitable organizations and is a founding member of The Scarlett Fund, which raises awareness and funds for pediatric research at Memorial Sloan Kettering.
Ms. Honts is a graduate from Bryant University with a Bachelor of Science degree in Business.
“We have great confidence in Reina’s leadership and vision as we embark on LCRF’s next chapter,” said Dr. Brendon Stiles, current vice chair and former chair of LCRF’s Board of Directors. “She has the energy and passion necessary to help LCRF achieve its ambitious goals for the next several years. As a lung cancer survivor, her empathetic point of view and drive to improve the lives of lung cancer patients are evident in her commitment to LCRF and the people it serves.”
Scott Morris
Scott Morris joined the LCRF Board of Directors on September 2, 2021.
Along with his immediate family, Mr. Morris is the caregiver to his mother who is living with lung cancer and is EGFR positive. He discovered LCRF when his mother was diagnosed with lung cancer in 2015 and a former colleague, who was 44 years old, died from lung cancer around that same time.
His support of LCRF includes helping LCRF acquire celebrity talent for its gala event, fundraising for the 2019 New York Free to Breathe Walk, and funding an LCRF grant related to the EGFR mutation research.
Mr. Morris is a graduate of Belmont University in Nashville, TN with a BBA degree in Music Business and is currently an agent for Creative Artists Agency (CAA), which he joined in 2012.
Mr. Morris brings the perspective of a caregiver, a passion for research, corporate and entertainment connections, fundraising prowess, and his own philanthropy to the LCRF Board of Directors.
“LCRF is delighted to have Scott on its board,” said Reina Honts, chair of LCRF’s Board of Directors. “His dedication to funding research and his caregiver’s perspective are exactly what is needed to help LCRF in meeting its commitments and mission.”
To learn more about LCRF and its Board of Directors, visit LCRF.org.
When Janae Bowie decided she wanted to hold a fundraiser in memory of her mother, Diane Minnick, volleyball rose to the top of the list.
Diane was diagnosed with non-small cell lung cancer in March 2020 at 61 years of age and passed away in December. Janae describes her as “a very caring, loving and selfless woman who always put others before herself. She touched many hearts in her community.” She also loved sports, including biking, playing pickle ball, and especially volleyball.
Diane’s cancer had the EGFR mutation, and Janae’s fundraiser went towards the EGFR Resisters/LCRF partnership to raise funds for new EGFR-positive lung cancer research projects. The memorial volleyball tournament took place Aug. 22 in Westminster, CO, and so far, has raised over $7,700.
Thank you to Janae, her family and friends for all their hard work and efforts into making this fundraiser a success!
LCRF board member Colleen Conner Ziegler was quoted in an article about lung cancer screening on BlackDoctor.org. She talked about her own experience of when she received a diagnosis of advanced lung cancer at age 58.
“It took a visit to the hospital after coughing up blood to receive an accurate diagnosis after a chest X-ray and CT scan revealed a mass in my lungs,” she said. “That is why as a cancer community we need to educate on risks and symptoms of the disease, especially in underserved populations, because lives truly depend on it.”
As fall 2021 approaches, we’ve seen a number of interesting developments in lung cancer research in the year so far.
Several new findings were introduced at the American Association for Cancer Research (AACR) and American Society for Clinical Oncology (ASCO) annual meetings. Another major conference, the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer, will take place Sept. 8-14.
To read the more comprehensive version of this update, click here.
Targeted therapies
Targeted therapies continue to be an area of potential new development.
Dr. Eugene Manley, Jr.
“Roughly, about 9-10 key driver mutations for lung cancer – specifically non-small cell lung cancer – are likely to indicate disease progression. A lot of the work presented at these national summits talked about some of the key developments in targeting these mutations,” said Eugene Manley, Jr., PhD, LCRF’s Director of Scientific Programs.
“We’ve learned about tumor biology and keep learning more,” he added. “Many tumors are what we call heterogeneous, which means they don’t all have the same types of cells.” This results in cells with different protein expression, gene expression, and even different transcription factors that affect how the cells grow, how they respond to therapies, and whether they might be sensitive to or resist therapies.
LCRF played a role in making molecular profiling standard of care during the 2nd iteration of the Lung Cancer Mutation Consortium. The 4th iteration, the LCRF LEADER trial, will soon be underway and will look at treatment in a neoadjuvant setting.
Dr. Kathryn Gold, UCLA
Kathryn Gold, MD, LCRF’s guest for July’s #TogetherSeparately Lung Cancer Mid-Year Update webinar, provided context on new drugs and targeted therapies, as well as disparities, drug resistance and the impact on patients. (Click here to view the webinar recording.)
“Because research has moved fast, we have a lot of approved therapies right now that have never been directly compared to each other, and that can make it kind of difficult to figure out what the best is for any one person,” Dr. Gold stated. As an example, she noted that five FDA approved drugs are available for patients with ALK-positive lung cancer: crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. While clinical trials have shown that the four newer drugs are likely more effective than crizotinib, “they’ve never been compared head-to-head versus each other,” she said. “So when I am seeing that brand-new diagnosis of ALK-positive lung cancer in a patient in my clinic, I have five options, which is great, but I don’t have anything to tell me which one is best.”
However, Dr. Gold noted that too many options is better than not having enough. “It’s a good problem to have,” she said.
The J-ALEX study compared alectinib and crizotinib in patients with the ALK mutation. “Earlier time points showed that alectinib treatment let to increased overall survival and progression-free survival, but the five-year data only showed better progression-free survival, not an increase in overall survival,” Dr. Manley said. “You get more time without the tumor returning, but in essence survival rates aren’t different after five years.” Having multiple drugs to target a mutation opens the possibility of using each drug successively. The CROWN study showed that in advanced ALK+ NSCLC, lorlatinib was much better than crizotinib for increasing progression-free survival rates and decreasing brain metastases.
EGFR is one of the most common mutations in non-small cell lung cancer. Osimertinib (Tagrisso) was granted FDA approval in December 2020 for EGFR-mutant NSCLC based on the ADAURA trial. In this trial, patients whose tumors tested positive for the EGFR mutation received either osimertinib or the previously standard care of regular CT scans with monitoring. While osimertinib reduced the risk of the tumor returning, it’s unclear whether the drug will help people live longer.
As Dr. Manley noted, “The results are significant because they made osimertinib the first personalized therapy in the adjuvant setting, and it can be used for early-stage patients with EGFR-positive lung cancer.”
Patients eventually develop resistance to osimertinib, and several trials had encouraging results targeting osimertinib-resistant NSCLC. In the CHRYSALIS trial, amivantamab combined with orally delivered lazertinib was shown to subsequently impede tumor growth. Another trial points to patritumab deruxtecan (HER3-DxD), an antibody drug conjugate (ADC), as a potential option. In an ADC, the antibody is used to home in on the tumor while attached to a chemotherapy drug. This approach is thought to more specifically target the tumor while minimizing systemic exposure or toxicity.
Patients with EGFR Exon 20 insertion mutations whose cancer had advanced on chemotherapy now have their first targeted therapy option. In May, the FDA approved amivantamab (Rybrevant), a monoclonal antibody delivered intravenously, to treat this rare mutation. This antibody had an unprecedented 40% response rate, increased survival rates, and was well tolerated.
The FDA granted the oral medication poziotinib Fast Track designation in March for use in patients with EGFR and HER2 Exon 20 mutations. While response rates are high for this drug, toxicity is a concern.
While KRAS is the most frequent mutation, found in 20-40% of NSCLC patients, the specific KRAS G12 mutation was thought to be undruggable until the FDA’s recent approval of sotorasib (Lumakras®). Sotorasib was found to be safe while shrinking tumors and improving survival for patients with this mutation who had previous systemic. A chemically similar therapy, adagrasib (MRTX849), was given FDA Breakthrough designation in June.
Other findings:
The combination of pertuzumab, trastuzumab, and docetaxel reduced tumor growth in patients with metastatic NSCLC with HER2 Exon 20 mutation.
After a COVID screening led to a patient’s NSCLC diagnosis, liquid biopsy was used to identify their cancer as RET-fusion positive. Treatment with selpercatinib (Retemvo) reduced the patient’s tumor mass.
The ARROW study showed that orally delivered pralsetinib (Gavreto) had strong antitumor activity in patients with advanced solid tumors harboring RET fusions, including NSCLC.
The GEOMETRY mono-1 trial showed that capmatinib is effective for MET Exon 14 (METex14) skipping NSCLC patients as a first-line therapy.
The VISION trial used tepotinib as treatment for patients with MET Exon 14 mutations detected with a Guardant360™ liquid biopsy. Tepotinib had some efficacy in patients with MET amplified NSCLC, which was a continuation of their results from an earlier study.
While more and more breakthroughs are happening around targeted therapies, not every patient’s cancer is being tested for multiple biomarkers.
The MYLUNG Consortium showed that in community-based settings, many in the southeastern US, 90% of tumors are tested for at least one of the most common biomarkers – ALK, BRAF, EGFR, ROS1, and PD-L1. But only 46% were tested for all five biomarkers prior to therapy, which means patients may not be receiving appropriate clinical trials or therapies.
“We’ve made it a lot of advances in the past 15 years, and I don’t think any of those would be possible without profiling of tumors,” said Dr. Gold. “Every single person with adenocarcinoma of the lung should get mutational profiling. And I think they should get a pretty broad panel, not only for EGFR, KRAS, ALK, but for all those less common ones, as well.”
Disparities in health care access continue to be an issue. The FLATIRON health database retrospective study showed that while there was no difference between white and Black patients in gene alterations, Black patients were 10% less likely to receive biomarker testing in general and 7% less likely to receive it before targeted therapy. Some of the barriers to testing include tissue limitations, provider education, and patient access. These differences also manifested in access to and enrollment in clinical trials, where white patients were twice as likely to be enrolled than Black patients.
“The biggest problem with that is if you don’t know what driver mutation they have before you start therapy, you may make it much worse,” Dr. Manley explained. “You could give them a drug they’re resistant to because of a mutation that you didn’t test.”
LCRF and the AME Church Health Commission announced a partnership this spring to increase lung cancer awareness, education, and screening in Black Americans to reduce mortality rates.
Immunotherapy
“Some really interesting data with immunotherapy and early-stage lung cancer was presented at ASCO,” Dr. Gold noted. Immunotherapy uses drugs “that try to persuade your body’s immune system to attack the cancer,” she explained. “It’s very commonly used in Stage IV lung cancer, and also in Stage III lung cancer after radiation, but had not yet been used in early stage lung cancer.”
The IMpower 10 trial studied a PD-L1 inhibitor, atezolizumab, in people who had lung cancers that were resected surgically and then treated with chemotherapy. The patients were randomized to either immunotherapy or standard of care, which was observation.
“Like the ADAURA trial showed, what we saw in this trial was that it did seem to reduce the risk of the tumor coming back,” Dr. Gold explained.
Watch Dr. Gold’s #TogetherSeparately mid-year update
Several other studies looked at combining chemotherapy and immunotherapy.
The Checkmate 816 trial compared nivolumab and platinum-doublet chemotherapy with chemo alone in patients with resectable NSCLC. Results showed that after four years, the combination was more effective at improving survival than chemotherapy alone in the neoadjuvant setting.
The two-year update for the Checkmate 9LA trial showed improved survival for patients with advanced NSCLC treated with a combination of nivolumab, ipilimumab and two cycles of chemotherapy, compared with treated four cycles of chemotherapy alone. This suggests that the combination therapy is effective as a first-line treatment option.
The Checkmate 227 trial presented four-year follow-up data of patients with advanced NSCLC with expression of PDL1 ≥ 1% or < 1% treated with nivolumab, ipilimumab, or the two drugs together. The combination was more effective in patients with both PD-L1 ranges compared to the solo therapies.
The FDA analyzed clinical trial data of approved therapies for advanced NSCLC patients with PD-L1 (1-49%) treated with immunotherapy alone or the combination of chemotherapy and immunotherapy. The combination led to better survival rates than immunotherapy alone as a first line treatment, but since these trials included a disproportionately low number (2%) of Black patients, we can’t conclude whether treatment will be effective in that population.
The PACIFIC trial presented a five-year update on patients with unresectable stage III NSCLC that had progressed following chemotherapy. The combination of durvalumab (Imfinzi) and chemoradiation increased overall survival and disease-free survival compared to the placebo.
NSCLC patients with high Tumor Mutational Burden (TMB) have a higher overall response rate and greater overall survival with immune checkpoint inhibitors when compared to those with intermediate or low TMB.
The use of antibiotics before or at the start of immune checkpoint inhibitors is associated with worse overall survival, which does not occur with chemotherapy.
Small Cell Lung Cancer
“With small cell lung cancer, it is still not the standard for patients to get profiling,” said Dr. Gold. “That’s unfortunately because most of the mutations that we find in small cell are not things that we know how to target with the medications that we have available to us right now.”
Recent work has showed that SCLC is not one distinct tumor but has several subtypes of cells that can be categorized into five groups: SCLC-A, SCLC-N, SCLC-P, and SCLC-I. SLCL-I is inflamed, which may predict sensitivity to immunotherapies. Other subtypes are linked with drug resistance.
Another group characterized these subtypes as SCLC-A, SCLC-N, SCLY-Y, SCLC-P, and SCLC-Mixed; and a third group identified three subtypes and found a marker, PLCG2, that may be associated with more metastatic tumors and worse outcomes.
Dr. Gold thinks that the future will bring more questions. For example, “drugs like sotorasib seem to work pretty well as a single agent. Can we make it better by combining it with immunotherapy? By combining it with chemotherapy? Maybe even moving it to the frontline setting? Those are the things that we’ll be talking about in a year. We have little teases of that data right now, but a year from now, I think we’ll have a lot more kinds of concrete data.”
Dr. David P. Carbone was our guest Aug. 18 for a #TogetherSeparately live talk on Why Biomarker and Genomic Testing Matters.
During the livestream, Dr. Carbone talked about the promise and successes of targeted therapies and immunotherapy, answered questions about oncogene mutations and available treatments, and outlined current studies that could be game-changers for lung cancer patients. Watch the video below.
