Advances in Non-Small Cell Lung Cancer: How Targeted Therapies Can Help Some Patients 

 What Is NSCLC?

Non-small cell lung cancers, or NSCLCs, are cancers of the cells lining the surface of the lung airways. Despite numerous treatment and diagnostic advances, lung cancer overall is still the leading cause of cancer-related death in the United States,¹ and the American Cancer Society projects that 2025 will see roughly 226,650 lung cancer diagnoses and about 124,730 deaths from the disease.³ Roughly 1 in 5 persons with any type of lung cancer is still alive 5 years after diagnosis.⁴

NSCLC is by far the most common lung cancer type, accounting for 85% of these cancers.⁵ NSCLC is less aggressive than other lung cancer types, but lung cancers can develop and linger in the lungs for years before coughing, shortness of breath, or other symptoms become noticeable.⁶ So, in 4 in 10 cases, an NSCLC will have spread beyond the lungs by the time it’s diagnosed.⁵

What Causes NSCLC?

Smoking, which causes as many as 90% of lung cancer deaths in the United States,⁷ is the most prevalent risk factor for NSCLC. The more extensive a person’s smoking history, the greater the risk of developing NSCLC.⁵ Exposure to secondhand smoke, or radon, workplace exposure to asbestos or chemicals, and air pollution are less common but still possible causes.⁸

Lung cancer typically begins when cells have specific genetic changes (called “mutations”) that alter their normal makeup and cause them to proliferate and form tumors. Targeted therapies act against cancerous cells or the biological processes that support their development and growth, and this stops the cancer from growing and spreading.⁹

Targeted therapies have been shown to prolong survival among patients with late-stage NSCLCs that have spread, with as many as 1 in 2 patients surviving 5 years after diagnosis depending on the genetic mutation.² The American Society of Clinical Oncology (ASCO) recommends use of different targeted therapies based on the mutation that is being targeted.²

Targeted Therapies for NSCLC

Several types of targeted therapies are approved for specific NSCLCs, and each type works differently. These include:

• Tyrosine kinase inhibitors (TKIs), which block the processes that allow cells to grow and divide.
• Antibody-drug conjugates (ADCs), which bind to cancer cells with help from the immune system. Once the cell and ADC are bound, the ADC releases chemotherapy into the cell and kills it. 
• Angiogenesis inhibitors, which starve cancer cells by stopping new cell growth. This type of targeted therapy is made from a monoclonal antibody, a laboratory re-creation of an immune system protein that targets cancer cells.⁹

Another type of targeted therapy, proteasome inhibitors, has been studied for NSCLC treatment,¹⁰ but none of these agents have yet been approved by the US Food and Drug Administration (FDA) for this use.

Targeted Therapy vs. Chemotherapy

Targeted therapy differs from standard chemotherapy, a systemic treatment that travels throughout the bloodstream and can kill cancer cells anywhere in the body.^9,11 In the process, chemotherapy can also attack healthy cells near the cancerous cells, and this can lead to bothersome side effects, most commonly hair loss and digestive discomfort.^9,11

By contrast, targeted therapy has less of an effect on nearby healthy tissue, which reduces – but does not eliminate – the side-effect risk.¹ Targeted therapies do cause side effects, with skin rash or dryness, changes in the nails, irritation or inflammation, fatigue, mild diarrhea, and nausea and vomiting among the most common.^1,12 

But as researchers continue to probe cancer-causing cellular changes and how to combat them, they’re also developing targeted therapies that more precisely target cancerous cells and cause fewer side effects. For example, the epidermal growth factor receptor (EGFR)–targeting TKI osimertinib, which was approved by the FDA in 2015,¹³ causes fewer side effects than the original EGFR inhibitors developed 20 years ago.¹

How Targeted Therapy Is Used – and for Which Patients

Targeted therapies typically are used to treat aggressive late-stage NSCLCs.^1,14 This therapy can be given alone or in combination with chemotherapy, immunotherapy, or another targeted agent depending on the mutation, the cancer’s aggressiveness, or the patient’s ability to tolerate multiple treatments.¹⁴

Not all patients with NSCLC are candidates for targeted therapy; only patients with NSCLC caused by a specific mutation are likely to respond to a targeted therapy formulated to address that genetic change. However, roughly 40% to 50% of patients with NSCLC have biomarkers that indicate their particular lung cancer would respond to a targeted therapy.¹ These biomarkers signal alterations in the following 10 genes:¹

• ALK
• BRAF
• EGFR
• HER2
• KRAS
• MET
• NTRK
• PDL1
• RET
• ROS1

EGFR and KRAS are the 2 most common types of mutations in NSCLC, accounting for about 40% of all alterations seen in this disease.¹ Some mutations are most prevalent among people in an ethnic or demographic group or based on patient characteristics.¹ For example, EGFR-driven lung cancers are most prevalent among women, Asians, and never-smokers, whereas KRAS and BRAF are most prevalent among current or former smokers.¹

If you’re battling NSCLC, your oncologist might recommend biomarker testing to determine whether you have a genetic mutation that could be targeted. 

Biomarker testing in NSCLC typically is done by removing a tissue sample from a tumor biopsy and analyzing it for mutations.¹⁵ Alternatively, a blood draw may be done if tissue samples are limited or cannot be obtained.¹⁵

Different types of biomarker tests are available.¹⁵ One type of test, next-generation sequencing, often is recommended in NSCLC because it can detect many biomarkers at one time.¹⁵ 

Biomarker testing also can detect presence of programmed death ligand 1 (PD-L1), a protein that cloaks cancer cells and keeps the immune system from destroying them. If a patient’s PD-L1 levels are above normal, that patient’s NSCLC may respond to a targeted immunotherapy.¹⁶

You and your oncologist should discuss biomarker testing before a biopsy is performed, so the doctor will know how much tissue to remove for the test.¹⁵ If the cancer continues to grow despite use of a targeted therapy, additional biomarker testing may be needed.¹⁵

The Future of Targeted Therapy

Researchers continue to explore use of targeted cancer treatment, and their findings could soon expand the treatment’s role in treating NSCLC and other lung cancers.¹ For example, researchers are investigating use of targeted agents for locally advanced, earlier-stage lung cancers.¹ Newer treatments that target additional mutations also are being developed, and this could make targeted treatment available to many more patients with NSCLC.¹

Explore Targeted Therapy for Cancer at RCCA

RCCA has more than 100 medical oncologists and hematologists who practice at 25 locations across New Jersey, Connecticut, Massachusetts, and the Washington, D.C., area. RCCA’s cancer specialists see more than 30,000 new patients each year and provide care to more than 265,000 established patients, collaborating closely with those patients’ other physicians. RCCA physicians offer patients innovative therapies, including immunotherapies and targeted therapy, as well as access to approximately 300 clinical trials. In addition to serving patients who have solid tumors, blood-based cancers, and benign blood disorders, RCCA care centers also provide infusion services to people with a number of non-oncologic conditions—including multiple sclerosis, Crohn’s disease, asthma, iron-deficiency anemia, and rheumatoid arthritis—who take intravenously administered medications.

To learn more about RCCA, call 844-346-7222 or contact us today.

References

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2. Jaiyesimi IA, Temin S, Singh N; ASCO Expert Panel. Therapy for stage IV non–small-cell lung cancer with and without driver alterations: ASCO Living Guidelines Q and A. JCO Oncol Pract. 2022;18(10):699-702. 
3. Key statistics for lung cancer. American Cancer Society. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html. Updated January 16, 2025. Accessed February 1, 2025.
4. Cancer Stat Facts: Lung and bronchus cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program. https://seer.cancer.gov/statfacts/html/lungb.html. Accessed January 29, 2025. 
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7. Lung cancer risk factors. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/lung-cancer/risk-factors/index.html#. Published October 15, 2024. Accessed February 1, 2025. 
8. Lung cancer in nonsmokers. Yale Medicine. https://www.yalemedicine.org/conditions/lung-cancer-in-nonsmokers. Accessed February 1, 2025. 
9. Targeted therapies for lung cancer. American Lung Association. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/treatment/types-of-treatment/targeted-therapies. Updated October 1, 2024. Accessed February 1, 2025.
10. Chua A, Thaarun T, Yang H, Lee A. Proteasome inhibitors in the treatment of nonsmall cell lung cancer: a systematic review of clinical evidence. Health Sci Rep. 2023;6(11):e1443. 
11. How is chemotherapy used to treat cancer? American Cancer Society. https://www.cancer.org/cancer/managing-cancer/treatment-types/chemotherapy/how-is-chemotherapy-used-to-treat-cancer.html#..UpdatedNovember 22, 2019. Accessed February 1, 2025.
12. How does targeted therapy work? UPMC Hillman Medical Center. https://hillman.upmc.com/cancer-care/medical-oncology/targeted-therapy/how-does-targeted-therapy-work. Accessed February 1, 2025.
13. Tagrisso [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 
14. Targeted drug therapy for non-small cell lung cancer. American Cancer Society. https://www.cancer.org/cancer/types/lung-cancer/treating-non-small-cell/targeted-therapies.html#. Updated January 28, 2025. Accessed February 1, 2025. 
15. Lung cancer biomarker testing. American Lung Association. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing. Updated October 2, 2024. Accessed February 1, 2025.
16. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1–positive non-small-cell lung cancer. N Engl J Med. 2016;375:1823-1833.