Newly-Approved Lorbrena Shows Better Responses in Patients With Brain Metastases

The Food and Drug Administration (FDA) recently expanded approval of Lorbrena (lorlatinib) for use as a first-line treatment option for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) that has also spread to the brain. That marks a step in the right direction for patients, but experts note there are still significant unmet needs.

“The difficulty we have is that the brain has a blood-brain barrier that protects itself from chemicals,” Dr. Shayma Kazmi, medical director of thoracic oncology at Cancer Treatment Centers of America in Philadelphia, said in an interview with CURE®. “So really, systemic treatments like chemotherapy, which we used to use up until five or six years ago, would not penetrate the brain very well.”

Brain metastases, or the spread of cancer cells from their original site to the brain, occurs in approximately one-third of patients with another type of cancer, according to estimates from Johns Hopkins Medicine. In general, research has shown that brain metastases are more common in certain cancers because of the biology of the disease. Lung cancer is one of the more common diseases that can spread to the brain.

Up to 40% of patients with lung cancer, according to Kazmi, develop brain metastases, and some already have it present at the time of initial diagnosis. In general, common symptoms patients should be aware of include headache, nausea, vision changes, clumsiness, forgetfulness and, under more serious circumstances, seizures.

Although it has been difficult to break the blood-brain barrier with conventional chemotherapies, there has been dramatic progress regarding treatment options for disease that has spread to the brain, Kazmi said. One is Lorbrena, which received an expanded approval on March 3. The drug had received an accelerated approval in November 2018 for the second- or third-line treatment of ALK-positive metastatic NSCLC.

The FDA based its decision to expand the indication of Lorbrena on data from the randomized, multicenter, open-label, active-controlled phase 3 CROWN trial, which was conducted in 296 patients with ALK-positive metastatic NSCLC. These patients had not previously received treatment for metastatic disease.

“The (trial) showed that Lorbrena, when compared to crizotinib (Xalkori), had better systemic responses, and almost 96% of patients didn’t have brain metastases at one year, versus the 60% from crizotinib,” Kazmi explained.

However, questions remain as to how to best treat metastases in metastatic NSCLCs that have no genetic mutation such as ALK or EGFR, according to Kazmi. “There’s still a significant unmet need,” she said.

Dr. Lecia Sequist, director of the Center for Innovation in Early Cancer Detection at Massachusetts General Hospital in Boston, questions how Lorbrena compares head-to-head with newer drugs such as Alecensa (alectinib) and Alunbrig (brigatinib), which are also showing to be effective. “These other available ALK drugs are exponentially better at getting into the brain compared with crizotinib,” she said.

Sequist noted that patients should be aware of a new set of possible side effects associated with Lorbrena use since the drug was specifically designed to get into the brain. “These can cause mental and personality side effects that are a little different than we’ve seen with other ALK drugs, but they are usually well managed by reducing the dosage and educating people about the types of side effects,” she said. Other symptoms patients should monitor are swelling of the feet and legs, weight gain and changes to the triglycerides that affect cholesterol.

When it comes to watching and treating brain metastases in general for patients with lung cancer, Sequist emphasized the importance of monitoring the brain along with the rest of the body — which can be difficult, depending on a patient’s insurance. For those patients who have not received a diagnosis of brain metastases, she recommends getting an MRI at least once a year, or every six months if they are on a drug that doesn’t also protect the brain, to monitor for disease spread.

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