Non-small cell lung cancer (NSCLC) is the most prevalent type of lung cancer, accounting for approximately 85% of all cases.

While conventional treatments, such as surgery, chemotherapy, and radiation therapy, have been the mainstay for many years, the emergence of immunotherapy has revolutionized the field of cancer treatment. Immunotherapy, which harnesses the body’s immune system to fight cancer, has shown promising results in improving outcomes for NSCLC patients.

Understanding Immunotherapy

Immunotherapy works by stimulating or enhancing the body’s immune response against cancer cells. It targets specific molecules or pathways involved in suppressing the immune system’s ability to recognize and destroy cancer cells.

One of the most widely used approaches in immunotherapy is immune checkpoint inhibitors.

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors are drugs that block the proteins on cancer cells or immune cells that prevent the immune system from attacking cancer cells.

These proteins, known as checkpoints, regulate immune responses to prevent the immune system from attacking healthy cells. In NSCLC, two checkpoint inhibitors have been approved by the FDA: pembrolizumab (Keytruda) and nivolumab (Opdivo).

Improved Overall Survival

Clinical trials have demonstrated the efficacy of immune checkpoint inhibitors in improving overall survival rates for NSCLC patients.

In a clinical trial comparing pembrolizumab with chemotherapy, patients who received pembrolizumab had a median overall survival of 16.7 months compared to 12.1 months with chemotherapy alone. Similarly, nivolumab has shown a significant improvement in overall survival compared to standard chemotherapy regimens.

Long-Term Responses

One of the most remarkable aspects of immunotherapy is its potential to produce long-term responses, known as durable responses, in patients with advanced NSCLC.

Unlike chemotherapy or targeted therapies, which often result in temporary tumor shrinkage, immunotherapy has been shown to provide sustained responses and even complete remission in some cases.

Combination Therapies

As the field of immunotherapy continues to evolve, researchers are exploring the use of combination therapies to further enhance treatment outcomes.

For example, combining immune checkpoint inhibitors with chemotherapy or other targeted therapies has shown improved response rates and progression-free survival in clinical trials.

Biomarkers for Patient Selection

Given the high cost and potential side effects of immunotherapy, identifying biomarkers that can predict patient response is crucial.

Biomarkers, such as PD-L1 expression, tumor mutation burden, and presence of specific genetic mutations, can help identify patients who are more likely to benefit from immunotherapy. These biomarkers also play a role in determining the optimal treatment regimen for individual patients.

Adverse Effects and Management

While immune checkpoint inhibitors have revolutionized NSCLC treatment, they can also cause immune-related adverse effects (irAEs). These adverse effects primarily occur due to the immune system becoming overactive and attacking healthy tissues.

Common irAEs include skin rash, diarrhea, endocrine dysfunction, and pneumonitis. Early recognition and management of these adverse effects are essential to ensure patient safety and treatment continuation.

Expanding Applications

Immunotherapy is not limited to advanced or metastatic NSCLC but is also being investigated for early-stage and locally advanced disease.

Clinical trials are exploring the efficacy of neoadjuvant or adjuvant immune checkpoint inhibitors in combination with surgery or radiation therapy to further improve outcomes in these patient populations.

Future Perspectives

As the understanding of the tumor microenvironment and immune response deepens, researchers are developing novel immunotherapy approaches, such as adoptive cell therapy, cancer vaccines, and immune agonists, to enhance antitumor immune responses.

These advancements have the potential to revolutionize NSCLC treatment further and offer hope for patients who have limited treatment options.