Posted: Friday, July 29, 2022
Nicolas Girard, MD, PhD, of Paris-Saclay University, Orsay, France, and colleagues assessed the safety and efficacy of the lorlatinib in the treatment of patients with anaplastic lymphoma kinase (ALK)-rearranged non–small cell lung cancer (NSCLC). Published in the European Journal of Cancer, the results of the IFCT-1803 LORLATU cohort showed that the ALK/ROS1 tyrosine kinase inhibitor not only provided a significant clinical benefit, but also demonstrated high intracerebral antitumor activity in a heavily pretreated population.
“The overall safety profile was favorable, although neurological side effects could lead to treatment discontinuation,” mentioned the study authors. “However, in ALK-positive NSCLC, first-line treatment is now based on second-generation ALK tyrosine kinase inhibitors, and the optimal sequencing of [these] inhibitors remains to be further analyzed.”
The investigators focused on 208 patients with advanced or metastatic ALK-positive NSCLC who were treated with lorlatinib between October 2015 and June 2019. Participant data were collected from medical records at 74 centers by staff of the French Thoracic Cancer Intergroup.
The median patient age was 60.9 years. Most individuals had stage IV NSCLC (87%) and were never-smokers (69%). Adenocarcinoma (94%) was the most frequent histology, and 77% of participants developed brain metastases. Lorlatinib was most commonly (49%) administered as the fifth or higher line of therapy in 49% of patients, followed by fourth-line (30%), third-line (17%), and second-line (4%) settings. Additionally, 94%, 93%, and 74% of participants were previously treated with a second-generation ALK tyrosine kinase inhibitor, first-generation ALK tyrosine kinase inhibitor, and chemotherapy, respectively.
At the median follow-up of 23.3 months, the median treatment duration was 11.8 months. The median progression-free survival, overall survival from treatment initiation, and overall survival from NSCLC diagnosis were 9.9, 32.9, and 97.3 months, respectively. The overall response rate was 49%, and the disease control rate was 86%; the central nervous system objective response rate was 56%. Of note, toxicity led to treatment discontinuation in 28 patients.
Disclosure: For full disclosures of the study authors, visit sciencedirect.com.