Targeted Drug Stops Lung Cancer Growth for Five Years in Over Half of People with Mutated Lung Cancer

A study shows that a targeted therapy drug stops the spread of lung cancer for 5 years or more. The drug, lorlatinib (Lobrena), also stops new cancer growth in the brain. These benefits were seen in 3 out of every 5 people with advanced non-small cell lung cancer (NSCLC) with an ALK gene mutation.

“This sets a new bar for targeted therapy in lung cancer and in other solid tumors,” said lead study author Benjamin Solomon, MBBS, PhD, Head of Lung Medical Oncology at the Peter McCallum Cancer Center in Melbourne, Australia. “The progression-free survival benefit seen with lorlatinib is unprecedented and vastly exceeds that reported with other ALK inhibitors or indeed any other targeted therapy in lung cancer.”

Results from this study were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Improving targeted therapy treatment for ALK-positive NSCLC

Between 3% and 5% of people are diagnosed with NSCLC that has changes to the ALK gene. This type of change is called a genetic mutation. When NSCLC has an ALK mutation, it is known as ALK-positive NSCLC.

ALK-positive NSCLC is treated with a type of targeted therapy called an ALK tyrosine kinase inhibitor (TKI). These medications target specific genes and proteins that help cancer cells survive and grow. ALK TKIs bind to ALK proteins to stop or slow the growth of cancer cells. There are 3 generations of ALK TKIs available to treat ALK-positive NSCLC. Even with the advances in treatments that target ALK mutations, many patients still have disease progression within 3 years, according to Dr. Solomon.  

Lorlatinib outperforms crizotinib at stopping lung cancer growth

The study included patients with advanced ALK-positive NSCLC who had not yet received treatment. Participants were randomly assigned to receive either lorlatinib or crizotinib (Xalkori). Both drugs are ALK TKIs that are approved by the U.S. Federal Drug Administration (FDA) to treat advanced ALK-positive NSCLC.

After 5 years of follow-up, median progression-free survival (PFS) for the 149 patients in the lorlatinib group was not yet reached. This means that more than half of the patients in the lorlatinib group have not had any new cancer growth. For every 5 patients in the lorlatinib group, 3 (60%) patients had no cancer growth after 5 years, and half were still receiving treatment.

In comparison, the median PFS was 9 months in the crizotinib group. This means that half of the participants had new cancer growth within 9 months. After 5 years, about 1 out of every 10 patients (8%) in the crizotinib group had no cancer growth and only 1 out of every 20 patients (5%) was still receiving treatment.

“Results from this study have been previously presented, but they are even more intriguing now that we have longer follow-up,” said ASCO expert Charu Aggarwal, MD, MPH, FASCO, the Leslye M. Heisler Associate Professor of Medicine at the University of Pennsylvania. “After following these patients for 5 years, the study results show that patients with ALK-positive NSCLC treated with lorlatinib can live longer without any disease progression, compared with crizotinib.” 

In the lorlatinib group, about 3 out of every 4 patients had side effects related to treatment. In the crizotinib group, more than half had side effects related to treatment. In both groups, about 1 of every 20 patients with side effects had to stop treatment because of them. The most common side effects were swelling caused by fluid trapped in tissues (edema), high cholesterol, and increased levels of lipids (hyperlipidemia).

Lorlatinib slows the spread of cancer to the brain

People with NSCLC with ALK mutations have a high risk of having the cancer spread to the brain. Around 1 out of every 4 patients had NSCLC that had spread to the brain when the study started. The median time to cancer growth in the brain was not reached in the lorlatinib group, compared to 16.4 months in the crizotinib group. In the lorlatinib group, 114 patients did not have cancer growth in the brain when the study started. Of those, only 4 had cancer spread to the brain during the 5 years the patients were followed.

“Lorlatinib is the only ALK TKI that has reported 5-year progression-free survival, and even after this time the majority of patients continue to have their disease controlled, including control of disease in the brain,” said Dr. Solomon.  

What this means for people with ALK-positive NSCLC

“This study underscores the importance of molecular testing in how we choose treatments for people with NSCLC,” said Dr. Aggarwal. Molecular testing, also called biomarker testing, identifies the genes, proteins, and other factors in the tumor. This can help doctors better match each patient with the most effective treatment possible.

Targeted therapy for NSCLC is changing quickly as more research into these treatments is being done. Recommended treatments may change as new information becomes available.

Talking to your cancer care team about molecular testing if you have NSCLC

Molecular testing is often part of the process for diagnosing NSCLC. If you have been diagnosed with NSCLC, consider asking your cancer care team these questions:

• Has molecular testing been ordered for me? Why or why not?
• Will I need another biopsy or blood-based test for molecular testing?
• Will treatment be delayed until my molecular testing results are back?
• Can the results of molecular testing help guide my treatment options?
• Are there clinical trials for me based on my molecular testing results?

Read a patient-friendly summary of this research.

Dr. Aggarwal is an Associate Editor on ASCO’s Patient Information Editorial Board.