Background and importance ALK gene mutation occurs in 3–5% of patients with non-small cell lung cancer (NSCLC). Brigatinib and alectinib are potent ALK tyrosine kinase inhibitors, indicated in NSCLC.
Aim and objectives The aim of this study was to perform an adjusted indirect treatment comparison (ITC) of the efficacy of brigatinib and alectinib in patients with NSCLC using a common comparator, and to establish whether both ALK inhibitors can be declared equivalent therapeutic alternatives (ETA).
Material and methods A search was carried out to detect clinical trials (CTs) with brigatinib or alectinib with similar populations, endpoints and follow-up periods. If multiple studies were found for the same drug, the results were combined in a meta-analysis using the Metasurv calculator. ITC was done according to Bucher’s method. To establish the positioning, ETA guidelines were applied. Delta value, maximum acceptable difference as a clinical criterion of non-inferiority, was set at 0.64 (and its inverse, 1.57) (the value used in the calculation of the sample size) for progression free survival (PFS). Shakespeare´s calculator was used to calculate the probability of the 95% confidence interval exceeding the delta margin.
Results Four CTs were included in the ITC for brigatinib (n=1) and alectinib (n=3). The CTs included were: phase III, randomised, open label, crizotinib controlled and ALK positive NSCLC. The endpoint was PFS (for Asian and non-Asian patients). Alectinib trials were pooled for Asian patients for PFS. The results of each trial, the combination and the conducted ITC are summarised in table 1.
The probability of the result being above or below the delta margin was, respectively, 10.28% and 15.7% for Asian patients, and 5.92% and 14.43% for non-Asian patients.
Conclusion and relevance ITC showed no statistically significant differences in PFS between brigatinib and alectinib for Asian and non-Asian patients. The extent of the 95% CI values showed some uncertainty. According to the ETA guidelines, as the percentage outside the delta margin was small, both drugs could be considered as ETA in most patients with ALK positive NSCLC.
Conflict of interest No conflict of interest
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