FDA Approves Lorbrena for Metastatic Non-Small Cell Lung Cancer Subtype

The Food and Drug Administration (FDA) granted accelerated approval to Lorbrena (lorlatinib) for the treatment of patients with ALK-positive, metastatic non-small cell lung cancer (NSCLC) who progressed on one or more ALK tyrosine kinase inhibitor (TKI), according to Pfizer, the drug’s manufacturer.

“The approval of Lorbrena is a perfect example of how we can use precision medicines to achieve our goals of making all cancer very personal to each individual,” Bonnie J. Addario, founder and chair of the Bonnie J. Addario Lung Cancer Foundation, said in an interview with CURE.

Specifically, Lorbrena is approved for patients who have progressed on Xalkori (crizotinib) and at least one other ALK inhibitor for metastatic disease; Alecensa (alectinib) as the first ALK inhibitor therapy for metastatic disease; or Zykadia (ceritinib) as the first ALK inhibitor therapy for metastatic disease.

“While many ALK-positive metastatic NSCLC patients respond to initial TKI therapy, they typically experience tumor progression,” according to a Pfizer press release. “Additionally, options for patients who progress after treatment with second-generation ALK TKIs, alectinib, brigatinib (Alunbrig) and ceritinib, are limited. The approval of Lorbrena represents a new option for patients who have progressed on a second-generation ALK TKI, providing an opportunity to remain on oral therapy.”

The approval was based on a nonrandomized, dose-ranging and activity-estimating, multicohort, multicenter phase 1/2 study — designed to evaluate Lorbrena in 215 patients with ALK-positive metastatic NSCLC who were enrolled across various subgroups based on prior treatment.

The agent induced an overall response rate of 48 percent, including a complete response rate of 4 percent and a partial response rate of 44 percent, and importantly, 57 percent had previous treatment with more than one ALK TKI. The median duration of response was 12.5 months.

In addition, 69 percent of patients had a history of brain metastases and intracranial response rate was 60 percent.

The most common side effects included edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects and diarrhea. Serious side effects occurred in 32 percent of patients, including pneumonia (3.4 percent), dyspnea (2.7 percent), pyrexia (2 percent), mental status changes (1.4 percent) and respiratory failure (1.4 percent).

Fatal side effects occurred in 2.7 percent of patients, including pneumonia (0.7 percent), myocardial infarction (0.7 percent), acute pulmonary edema (0.3 percent), embolism (0.3 percent), peripheral artery occlusion (0.3 percent) and respiratory distress (0.3 percent). Eight percent of patients permanently discontinued treatment, approximately 48 percent of patients required dose interruptions and 24 percent required at least one dose reduction.

Pfizer noted this indication for Lorbrena is approved under accelerated approval based on tumor response rate and duration of response, and continued approval may be contingent upon the verification and description of clinical benefit in a confirmatory trial.

The FDA-recommended dose of Lorbrena is 100 mg orally once daily.

“Just a few short years ago, lung cancer research was seriously lagging behind the other top four cancers. It is now leading the way in innovation and research,” Addario said. “We must continue to move at this rapid pace to bring more therapies like lorlatinib to patients. It means extended life and is a pathway to personalized medicine by using precision medicine and collaboration among all stakeholders.”