Thoracic medical oncologist Dr. Mark Awad says new treatments for lung cancer include a growing number of targeted therapies and new forms of immunotherapy.
Lung cancer is the second-most common cancer and remains the leading cause of cancer death in the United States. But a variety of new treatments, many of them developed or tested at Memorial Sloan Kettering Cancer Center (MSK), are helping to bring down the number of deaths.
We recently spoke with Mark Awad, MD, PhD, Chief of MSK’s Thoracic Oncology Service about the latest advances in lung cancer treatment and the advantages of coming to MSK when you are first diagnosed.
How is the treatment of lung cancer changing?
Exciting new treatments have emerged in recent years — both for early-stage tumors (stage 1, 2, or 3) that can be surgically removed, and for more advanced stage 4 lung cancers that have spread (metastasized).
Non-Small Cell Lung Cancer Advances
Advances in treating stage 1, 2, or 3 NSCLC
Non-small cell lung cancer (NSCLC) is by far the most common type of lung cancer, compared with small cell lung cancer (SCLC). When detected early, NSCLC is usually treated by surgery, and MSK offers minimally invasive options that can speed recovery. If you have early-stage NSCLC, our surgeons will remove the tumor while sparing as much of the healthy lung as possible.
At MSK, more than 90% of lung cancer surgeries for early-stage disease (stage 1) now use minimally invasive approaches such as video-assisted thoracic surgery (VATS) and robotic-assisted surgery. This usually results in less pain and fewer complications. It also enables patients who may need chemotherapy or radiation therapy to start treatment sooner.
Advances in treating stage 4 NSCLC
Many lung cancers are diagnosed at stage 4, after they have already spread to other parts of the body. For people with later-stage cancers, many new treatment options have been developed. These include new chemotherapy treatments, new targeted therapies that are matched to specific genetic mutations found within the lung cancer tumor, new immunotherapies, and novel cellular treatments.
How is MSK using genetic testing to determine the treatment for lung cancer?
We perform comprehensive genetic testing of tumors in all patients with non-small cell lung cancer. This is now a routine part of diagnosis and staging for every MSK patient with NSCLC. We are one of only a handful of centers in the world with in-house genomic testing for hundreds of potential gene mutations. This is a crucial step in the workup of lung cancer because finding the right treatment requires finding potential molecular changes causing the cancer. This is why I truly believe patients are better off when they come to MSK — to ensure that their cancer is tested with the most cutting-edge sequencing technologies available.
The analyses we do at MSK allow us to make a more nuanced diagnosis and determine the vulnerabilities of a specific cancer. Based on what we find in your tumor, we may have an approved targeted therapy that’s effective against the mutations that are driving your cancer’s growth. Or you may be able to join a clinical trial that is testing a new drug or combination of drugs.
How are new targeted therapies for specific genetic mutations improving lung cancer treatment?
We are getting new targeted therapies approved every year for genes that were long thought to be “undruggable.” For example, the cancer gene KRAS is responsible for about one-quarter of lung cancers. Scientists had studied it for almost 40 years but were unable to develop effective treatments. But research published in 2016 by MSK physician-scientists Piro Lito, MD, PhD, and Neal Rosen, MD, PhD, showed how it was possible to target KRAS in cancer cells — a major breakthrough.
By 2021, we had approval for the first KRAS-targeting drug in non-small cell lung cancer. This drug, called sotorasib (Lumakras™), is available for adult patients with a specific mutation called KRAS G12C. Another drug called adagrasib (Krazati®) was also recently approved for these mutations.
In addition to KRAS, there are many other lung cancer genetic mutations for which we have approved treatments. They include EGFR, ALK, ROS1, BRAF, RET, MET, NTRK, and HER2. We have also found additional mutations that are responding to new drugs that are currently in clinical trials.
Our goal for people with metastatic lung cancer is to help them live much longer, with a much higher quality of life that isn’t disrupted by the cancer therapy.
What’s the latest on immunotherapy to treat lung cancer in 2025 and beyond?
Several forms of immunotherapy to treat lung cancer have become the standard of care or are being tested in clinical trials:
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Checkpoint Inhibitors: A class of immunotherapy drugs called checkpoint inhibitors are often prescribed as an initial treatment for lung cancer, either alone or in combination with chemotherapy. We also now give immunotherapy before surgery to shrink tumors and help prevent recurrence of cancer after surgery. MSK’s surgeons and medical oncologists played an important role in the first clinical trial testing the effectiveness of this approach. In many cases, that means no cancer cells are left behind after the tumor is taken out.
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TIL Therapy: A new type of immunotherapy called TIL therapy is also showing promise. TIL (pronounced “till”) stands for tumor-infiltrating lymphocytes, a specialized type of white blood cell. The approach involves removing TIL cells from the tumor, growing them into large numbers outside the body, and then putting them back into the patient. There, the TIL cells can seek out and destroy cancer cells anywhere in the body. In 2024 MSK lung cancer specialist Adam Schoenfeld, MD, reported results from a clinical trial showing that TIL therapy was effective in some patients with small cell lung cancer.
- Lung Cancer Vaccines: We have two clinical trials testing a therapeutic lung cancer vaccine after surgery to prevent recurrence of non-small cell lung cancer. The approach is similar to a vaccine being tested in pancreatic cancer using messenger RNA (mRNA). After surgery, tumor samples are used to design a personalized vaccine based on the specific mutations in the individual patient’s cancer. The vaccine is given along with the checkpoint inhibitor pembrolizumab to prevent the lung cancer from returning. One trial is actively enrolling at MSK, and the other will likely begin enrolling in 2025. The Olayan Center for Cancer Vaccines at MSK, recently established, will help support the development of more lung cancer vaccines going forward.
New Immunotherapy Treatments for Small Cell Lung Cancer
For small cell lung cancer (SCLC), which is less common than NSCLC, immunotherapy is now added to standard drugs. In addition to checkpoint inhibitors, a new immunotherapy drug called tarlatamab (Imdelltra™) was recently approved for SCLC. It targets a protein on cancer cells called DLL3.
Physician-scientist Charles M. Rudin, MD, PhD, has been at the forefront of developing and testing new SCLC treatments. A collaboration between the lab of Dr. Rudin and radiochemist Jason S. Lewis, PhD, has led to a new imaging technique that detects DLL3 on cells. This could help identify patients who might respond well to tarlatamab and similar drugs that target DLL3.
Early detection and screening improves lung cancer survival rates
The best way to improve the prognosis for lung cancer is early detection. According to the American Cancer Society, the overall five-year survival rate for non-small cell lung cancer is 28%. But if detected early, the rate jumps to 65%.
Smoking remains a high-risk factor for lung cancer. For current and former smokers, MSK’s Lung Cancer Screening Program provides low-dose lung CT screening to current and former smokers. We hope to encourage more people to take advantage of this important screening tool, which is still greatly underused.
Our researchers are investigating other new methods for early detection:
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A team led by MSK thoracic surgeon Gaetano Rocco, MD, is testing a screening method known as “E-nose.” Still in an experimental phase, this device detects certain chemical compounds in a person’s breath that indicate lung cancer may be developing.
- Our researchers are helping to develop noninvasive tests known as “liquid biopsies,” which can detect the presence of cancer cells, or DNA from these cells called circulating DNA (ctDNA), that may linger after surgery. Liquid biopsies are already used in the treatment of stage 4 lung cancers, which produce high levels of ctDNA. Because early-stage lung cancers do not shed much DNA, thoracic surgeon James M. Isbell, MD, is leading a trial of a liquid biopsy test that analyzes the entire cancer cell genome. It looks for multiple genetic variants on the same fragment of ctDNA. This greatly increases the power of the test, enabling it to conclusively identify cancer DNA even in the tiniest amounts.
We are still in the early days of these newer approaches, but they could make a huge difference in early detection — in 2025 or beyond. If these tests could be routinely offered by primary care physicians, they would catch many lung cancers when the disease is easier to treat.
Overall, it’s an exciting time, and we’ve seen tremendous progress in the treatment of lung cancer. My colleagues and I are exclusively focused on treating this disease, and even within lung cancer, there are important advantages to going to a place with subspecialization based on the different genomic subtypes. MSK has always been at the forefront of exploring new approaches to save more lives and improve their quality.
