Lorbrena for previously-treated ALK-positive metastatic non-small cell lung cancer, approved from FDA
The FDA ( U.S. Food and Drug Administration ) has approved Lorbrena ( Lorlatinib ), a third-generation anaplastic lymphoma kinase ( ALK ) tyrosine kinase inhibitor ( TKI ) for patients with ALK-positive metastatic non-small cell lung cancer ( NSCLC ) whose disease has progressed on Crizotinib and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on Alectinib or Ceritinib as the first ALK inhibitor therapy for metastatic disease.
This indication has been approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The approval was based on a non-randomized, dose-ranging and activity-estimating, multi-cohort, multicenter phase 1/2 study, B7461001, evaluating Lorlatinib for the treatment of patients with ALK-positive metastatic NSCLC, who were previously treated with one or more ALK TKIs.
A total of 215 patients with ALK-positive metastatic NSCLC were enrolled across various subgroups based on prior treatment.
Among these patients, overall response rate ( ORR ) was 48% ( 95% CI: 42%, 55% ) and importantly, 57% had previous treatment with more than one ALK TKI.
In the trial, 69% of patients had a history of brain metastases and intracranial response rate was 60% ( 95% CI: 49%, 70% ).
Among 295 ALK-positive or ROS1-positive metastatic NSCLC patients who received Lorlatinib 100 mg once daily in study B7461001, the most common ( greater than or equal to 20% ) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.
The most common ( greater than or equal to 20% ) laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.
Serious adverse reactions occurred in 32% of the 295 patients. The most frequent serious adverse reactions reported were pneumonia ( 3.4% ), dyspnea ( 2.7% ), pyrexia ( 2% ), mental status changes ( 1.4% ), and respiratory failure ( 1.4% ).
Fatal adverse reactions occurred in 2.7% of patients and included pneumonia ( 0.7% ), myocardial infarction ( 0.7% ), acute pulmonary edema ( 0.3% ), embolism ( 0.3% ), peripheral artery occlusion ( 0.3% ), and respiratory distress ( 0.3% ).
Permanent discontinuation of Lorlatinib for adverse reactions occurred in 8% of patients; approximately 48% of patients required dose interruptions and 24% required at least one dose reduction.
Lorbrena is indicated for the treatment of patients with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer whose disease has progressed on Crizotinib ( Xalkori ) and at least one other ALK inhibitor for metastatic disease; or whose disease has progressed on Alectinib ( Alecensa ) or Ceritinib ( Zykadia ) as the first ALK inhibitor therapy for metastatic disease. ( Xagena )
Source: Pfizer, 2018