Cancer Treatment Today

On November 4, 2018m, the FDA has granted lorlatinib (Lorbrena) an accelerated approval for the treatment of patients with ALK-positive metastatic non–small cell lung cancer (NSCLC) who have progressed on 1 or more ALK tyrosine kinase inhibitors (TKIs).

Originally discovered as an oncogenic driver in a type of lymphoma, ALK gene alterations were also found to be among key drivers of tumor development in cancers, such as NSCLC.In ALK-positive lung cancer, a normally inactive gene called ALK is fused with another gene. This genetic alteration

creates the ALK fusion gene and ultimately, the production of an ALK fusion protein, which is responsible for tumor growth.This genetic alteration is present in 3-5% of NSCLC patients

Specifically, lorlatinib is approved for patients who have progressed on crizotinib (Xalkori) and at least 1 other ALK inhibitor for metastatic disease; alectinib (Alecensa) as the first ALK inhibitor therapy for metastatic disease; or ceritinib (Zykadia) as the first ALK inhibitor therapy for metastatic disease.

The approval is based on a nonrandomized, dose-ranging, multicohort, multicenter phase II study (B7461001) that included a subgroup of 215 patients with ALK-positive metastatic NSCLC previously treated with ≥1 ALK kinase inhibitors. The overall response rate with lorlatinib in these 215 patients was 48% (95% CI, 42-55), including a complete response rate of 4% and a partial response rate of 44%. The median duration of response was 12.5 months (95% CI, 8.4-23.7).

The FDA-recommended dose of lorlatinib is 100 mg orally once daily. NCCN the panel.

NCCN consensus supported the addition of lorlatinib as a treatment option
for ALK-positive metastatic NSCLC after progression on crizotinib
and alectinib, brigatinib, or ceritinib (NSCL-22) OR after progression
on alectinib, brigatinib, or ceritinib (NSCL-23).
The panel consensus supported a category 2A recommendation.

Wu J, Savooji J, Liu D. Second- and third-generation ALK inhibitors for non-small cell lung cancer. J Hematol Oncol. 2016;9:19.

Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with
ALK-positive nonsmall-cell lung cancer: results from a global
phase 2 study. Lancet Oncol 2018 Nov 6.

Lobrena, Persribing Information 2018