Abstract
BACKGROUND
Lung cancer has been the leading cause of cancer death for both men and women worldwide. Non-small-cell lung cancer (NSCLC) displays an array of molecular abnormalities most commonly involving ALK and EGFR pathways. NSCLC with ALK rearrangements comprises close to 5% of cases. Several ALK inhibitors (ALKI) have been approved with activity in brain metastases. However, there have been limited comparative studies exploring their relative efficacies. This meta-analysis was conducted to compare the relative efficacy of ALKIs against ALKI-naïve ALK+ lung cancer brain metastases.
METHODS
A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language; diagnosis of ALKI-naïve ALK+ lung cancer trials with brain metastases; treatment with Crizotinib (CRZ), Alectinib (ALC), Brigatinib (BRG), and Ceritinib (CER); and comparative studies reporting brain metastases specific responses/events. A Bayesian and a frequentists network meta-analysis were conducted using netmeta package and the random-effects model.
RESULTS
Eight studies comprising a total of 665 participants with ALKI-naive ALK+ lung cancer brain metastases were included. When compared pair-wise to CRZ, ALC (RR=0.49;95%CI:0.36–0.66), BRG (RR=0.39;95%CI:0.24–0.64), and CER (RR=0.36;95%CI:0.19–0.68) demonstrated significantly superior response rates in patients with untreated or previously treated lung cancer brain metastases. When the efficacy of each ALKI was compared to each other, BRG and CER were ranked the highest, followed by ALC and CRZ in decreasing order.
CONCLUSIONS
This network meta-analysis is the first to compare and rank approved ALKIs used in treating metastatic ALK+ lung cancer. It indicates that BRG, CER, and ALC are better therapeutic options for patients with ALK-naive ALK+ lung cancer brain metastases when compared to CRZ.