Emerging Lung Cancer Treatments: The Next Generation of Precision Care

Lung cancer is the second most common cancer and the leading cause of cancer death in the United States.¹ Yet treatment has advanced significantly, giving patients more options and helping people live longer. Doctors can now match some treatments to the specific features of a tumor, while newer immunotherapies help the immune system recognize and attack cancer.

These new options are part of a much broader wave of lung cancer research. Our experts at Private Health Management (PHM) closely follow therapies that are currently in development. Here, we highlight several investigational approaches that may shape the next generation of lung cancer care.

Understanding lung cancer and personalized treatment

There are two main types of lung cancer. Non-small cell lung cancer (NSCLC) is the most common and includes several subtypes, such as adenocarcinoma and squamous cell carcinoma. Small cell lung cancer (SCLC) is less common but generally grows and spreads more quickly. It is important to know which type a person has because they behave differently and are treated in different ways.

The best treatment strategy also depends on the biological features of the tumor. Even lung cancers of the same type can be driven by different changes within their cells that help the cancer grow or survive. Targeted therapies are designed to block those specific signals, which can make them highly effective for patients whose tumors have the right target.

To identify these changes, doctors can use comprehensive molecular profiling. These tests examine a tumor for many genomic changes at once, using tumor tissue and, in some cases, a blood-based liquid biopsy. Other biomarker tests can help determine whether immunotherapy may be appropriate. The results may point to an approved treatment or a clinical trial designed for that particular cancer.

More precise targeted treatments for NSCLC

Targeted therapy has been one of the most important advances in treating NSCLC. These drugs are designed to block specific proteins or signals that help a cancer grow. When the right treatment is matched to the right tumor, responses can be substantial and long-lasting.

KRAS is one of the most common cancer-driving mutations in NSCLC. For decades, it was considered nearly impossible to target with drugs. The first approved KRAS therapies work against only one specific form, called KRAS G12C. Researchers are now testing drugs for other KRAS mutations, including zoldonrasib for KRAS G12D, as well as treatments with broader reach.³

One example is daraxonrasib, which blocks several active RAS proteins. The drug was recently FDA-approved⁴ for certain patients with metastatic pancreatic cancer and is also being studied as a treatment for lung cancer. In an early trial, it shrank tumors in more than 30 percent of patients with RAS-mutated NSCLC whose cancer had progressed after chemotherapy and immunotherapy.⁵

EGFR is another common cancer driving mutation in NSCLC, and EGFR-targeted therapies are among the most established treatments for patients whose tumors have common EGFR mutations. However, less common EGFR mutations and cancers that become resistant to targeted treatment remain challenging. In a recent study, adding an investigational EGFR-targeting drug (zipalertinib) to chemotherapy delayed cancer progression by about six months compared with chemotherapy alone in patients with a less common EGFR mutation.⁶

Other molecular targets are also advancing, including:

• HER2: A HER2-directed treatment (trastuzumab deruxtecan) helped delay cancer progression in patients receiving their first treatment for advanced NSCLC.⁷
• ROS1: A newer targeted therapy (zidesamtinib) has shown strong activity, including against cancer that has spread to the brain.⁸
• ALK: Seven-year follow-up of patients receiving an ALK targeted drug (lorlatinib) showed long-lasting control of advanced NSCLC, including cancer in the brain.⁹
  

The next generation of immunotherapy for NSCLC

Immunotherapy helps the body’s immune system recognize and attack cancer. Checkpoint inhibitors are widely used immunotherapies for NSCLC that block some of the signals cancer cells use to hide from the immune system. However, they do not work for everyone, and some cancers eventually begin growing again. These limitations are driving research into a new generation of treatments that engage the immune system in different ways.

One approach under investigation uses bispecific antibodies, which target two pathways at once to strengthen the immune response. One of these treatments (ivonescimab) targets a pathway that cancer can use to evade immune attack (PD-1) and a protein that helps tumors develop a blood supply (VEGF). In a recent study, it helped certain patients with advanced NSCLC live longer than those treated with an established checkpoint inhibitor (pembrolizumab).¹⁰

New approaches for SCLC

SCLC has historically had fewer treatment options than other types of lung cancer. Researchers are now developing treatments that recognize proteins found on the surface of many SCLC cells. These proteins can act like markers, helping a treatment to target cancer cells while limiting its effects on healthy tissue.

One such treatment is tarlatamab, an immunotherapy that helps the body’s immune cells find and attack SCLC cells with a protein called DLL3. It is FDA-approved for extensive-stage SCLC that has progressed after chemotherapy.¹¹ Researchers are now studying whether it could help earlier in treatment.¹²

Another approach uses treatments called antibody-drug conjugates, or ADCs. These treatments pair an antibody that recognizes a marker on a cancer cell with a cancer-killing drug, delivering it directly to cells carrying that marker. In two recent studies, investigational ADCs that target a protein called B7-H3 helped people with relapsed SCLC live longer than treatment with a standard chemotherapy.^13,14

What these advances mean for patients

Lung cancer treatment is becoming more personalized, placing a greater emphasis on comprehensive molecular testing to identify available treatment options and determine the best sequence of treatments to improve patient care and outcomes. Some therapies discussed here are FDA-approved, while others are still being studied and may not ultimately become available. Even encouraging early results must be confirmed to show that the treatments are safe and effective. The best treatment strategy depends on the type and stage of lung cancer, molecular test results, previous treatments, overall health, and whether the cancer has spread to the brain. Clinical-trial searches may be valuable at diagnosis, at recurrence, and whenever a new treatment decision is being considered.

PHM helps clients obtain comprehensive testing, seek input from experienced lung cancer specialists, understand established and emerging treatment options, and identify clinical trials relevant to the specific features of their cancer. Individualized guidance can help patients and families make informed decisions as the science evolves.