FDA Approves Lorbrena as First-Line Treatment for ALK-Positive Non-Small Cell Lung Cancer

Pfizer announced that the Food and Drug Administration (FDA) approved a supplemental new drug application for Lorbrena (lorlatinib), which expands the indication of this drug to include first-line treatment for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer.

This action by the FDA updates the previous accelerated approval of the drug from 2018 to a full approval, according to a news release from the company. Lorbrena is indicated for adults with metastatic non-small cell lung cancer with ALK-positive tumors.

“For more than a decade, Pfizer has been a pioneer in delivering biomarker-driven therapies and addressing the diverse and evolving needs of people with non-small cell lung cancer,” said Andy Schmeltz, global president of Pfizer Oncology, in the release. “Lorbrena has been a transformative medicine for people with ALK-positive advanced (non-small cell lung cancer), and this FDA approval in the first-line setting means that we can now extend hope to even more people.”

Lorbrena is an ALK inhibitor that prevents common tumor mutations from increasing the body’s resistance to certain medications, which can lead to metastases (or disease spread) to the brain. An estimated 40% of patients with ALK-positive metastatic non-small cell lung cancer have brain metastases when they original receive a diagnosis, according to the release.

The expanded approval of the drug was based on results from the phase 3 CROWN trial, which included 296 people with previously untreated advanced ALK-positive non-small cell lung cancer. Patients were assigned either Lorbrena (149 patients) or Xalkori (crizotinib; 147 patients). Lorbrena reduced the risk of disease progression or death by 72% compared with Xalkori (crizotinib).

The CROWN trial also included patients with measurable brain metastases in the Lorbrena (17 patients) and the Xalkori (13 patients) groups. Patients assigned Lorbrena had a greater intracranial objective response rate compared with those assigned Xalkori (82% versus 23%). Intracranial duration of response lasting 12 months or longer was observed in 79% of patients in the Lorbrena group compared with 0% of those in the Xalkori group.

“The CROWN data have shown Lorbrena can significantly improve outcomes in the first-line treatment of ALK-positive non-small cell lung cancer, including those that present with brain metastases,” said Dr. Benjamin Solomon, of the department of medical oncology at Peter MacCallum Cancer Centre in Melbourne, Australia, in the release. “This approval is meaningful for my patients because we now have a highly effective treatment option that can delay the progression of a typically aggressive disease.”

Common side effects observed in the CROWN trial in patients that were assigned Lorbrena included weight gain, swelling, cognitive effects, peripheral neuropathy (weakness or numbness in hands and feet), shortness of breath, diarrhea, and high triglyceride levels. Some serious side effects were also seen in patients taking Lorbrena, including shortness of breath, pneumonia, cognitive effects, respiratory failure and fever. Fatal side effects occurred in 3.4% of patients and included respiratory failure, pneumonia, pulmonary embolism, cardiac failure and sudden death.

The FDA originally approved Lorbrena in 2018 for the treatment of patients with ALK-positive metastatic non-small cell lung cancer and whose disease progressed with Xalkori and another ALK inhibitor for metastatic disease, according to the release. This approval also included patients whose disease progressed on Alecensa (alectinib) or Zykadia (ceritinib) as the first ALK inhibitor for the treatment of metastatic disease.

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