FDA Approved Lorlatinib for ALK-Positive Metastatic NSCLC
A third generation TKI.
Approved for the treatment of patients who have metastatic non–small-cell lung cancer (NSCLC) that is ALK mutation positive and which progressed with crizotinib and at least 1 other ALK inhibitor or with alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
A potent orally available, CNS penetrant, selective ROS1TKI.
Has efficacy in ROS1 positive lung cancer.
Trade name Lorbrena.
The overall response rate is 48% with 4% complete and 44% partial responses.
The estimated median response duration in the trail was 12.5 months.
The intracranial overall response rate in 89 patients with measurable lesions in the central nervous system was 60% with 21% complete and 38% partial responses.
The estimated median response duration was 19.5 months.
High potent, brain penetrate TKI that inhibits ALK, ROS1 and most of the ALK resistance mutations, including Gly1202Ar.
The most common adverse reactions are: edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.
More potent than preceding inhibitors on biochemical and cellular assays, and it has the broadest coverage of ALK resistant mutations.
Has high exposure to the CNS.
In patients previously untreated with advanced ALK-positive NSCLC, who received Lorlatinib had significant longer progression free survival in patients who receive Crizotinib.
Frequently alters lipids.
More potent than preceding inhibitors on biochemical and cellular assays, and it has the broadest coverage of ALK resistant mutations.