OBJECTIVES : Alectinib is the current standard of care in 1^st line (1L) ALK+ NSCLC, however other ALK inhibitors have also demonstrated efficacy in this patient population, including most recently brigatinib. Currently there is limited head to head trial data comparing newer 2^nd generation ALK inhibitors. This study examined the relative efficacy and probabilities of the best treatments for 1L ALK+ NSCLC.

METHODS : A systematic literature review was conducted to identify the randomized controlled studies which examined the relative efficacy of ALK inhibitors. Outcomes included progression-free survival (PFS), overall survival (OS), and cumulative incidence of CNS progression (CNS). A Bayesian fixed-effects model was used to estimate treatment effects. As a sensitivity analysis, a random-effects model was implemented based on prior assumptions around study heterogeneity. 95% credible intervals were calculated from the posterior distribution of direct and indirect comparisons. Rankograms and surface under the cumulative rank curves (SUCRA) were calculated to summarize the treatment ranking probabilities.

RESULTS : Of the 4 studies identified in the literature review, 3 studies were included in the network comprising 4 treatments (alectinib, brigatinib, crizotinib and chemotherapy). Pairwise comparisons demonstrated that alectinib had directionally better efficacy for all 3 outcomes examined when indirectly compared to brigatinib (HR[95% CrI]; PFS: 0.86 [0.48, 1.52], OS: 0.78 [0.35, 1.7], CNS: 0.53 [0.23, 1.26]). Rankograms showed alectinib had the highest probability of being the best treatment for all 3 outcomes (PFS: 70.5%; OS: 69.5%; CNS: 92.4%). Alectinib had the highest SUCRA estimate (PFS: 95.1%; OS: 92.2%; CNS: 98.1%), followed by brigatinib in most cases (PFS: 88%; OS: 64.7%; CNS: 76.9%). Random-effects modeling showed similar results.

CONCLUSIONS : To date, alectinib demonstrated a trend toward the best efficacy in the three outcomes examined. However, further research is warranted as additional follow-up from brigatinib trials become available.