The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis

Abstract

BackgroundAlectinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer. We performed this meta-analysis to synthesize the results of different clinical trials to evaluate the efficacy and safety of alectinib.MethodsA search of 3 databases, including PubMed, Web of Science, and the Cochrane Library, was performed from the inception of each database through September 5, 2017. We have pooled the overall response rate (ORR), disease control rate, progression-free survival, and intracranial ORR to evaluate the efficacy of alectinib. Discontinuation rate, rate of dose reduction or interruption due to adverse events as well as the incidence of several adverse events were aggregated to evaluate its safety.ResultsA total of 8 studies with 626 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 70% (95% CI: 57% to 82%), disease control rate 88% (95% CI: 82% to 94%), progression-free survival 9.36 months (95% CI: 7.38% to 11.34%), and intracranial ORR 52% (95% CI: 45% to 59%). ALK inhibitor-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate discontinuation rate is 7% (95% CI: 4% to 10%), and the pooled rate of dose reduction or interruption is 33% (95% CI: 24% to 42%). The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18%) and anemia (25%), were even higher than with the first-generation ALK inhibitor crizotinib.ConclusionGenerally, alectinib is a drug with preferable efficacy and tolerable adverse effects, and it is suitable for the treatment of intracranial metastases.

The efficacy and safety of ALK inhibitors in the treatment of ALK‐positive non‐small cell lung cancer: A network meta‐analysis

“…Single‐arm meta‐analyses showed that the discontinuation rates were lower for alectinib and brigatinib (7%) than for ceritinib and crizotinib (8%), and lorlatinib had the lowest discontinuation rate (3%) (Figure ). Some previous studies have analyzed the safety of crizotinib and alectinib . Next‐generation ALK inhibitors appear to have better safety profiles.…”

“…Some previous studies have analyzed the safety of crizotinib and alectinib. 12,13 Next-generation ALK inhibitors appear to have better safety profiles. However, some parameters, including the proportion of people who need dose reduction or interruption, are not reported in all studies, and there are limited numbers of published studies of some next-generation ALK inhibitors (lorlatinib, ensartinib, etc.).…”

“…However, direct head‐to‐head clinical trials of the efficacy and safety of different ALK inhibitors are limited . Only four meta‐analysis studies have analyzed the efficacy and safety of ALKi (two studies on crizotinib, one on alectinib and one on overall ALKi) for treating ALK‐positive NSCLC . Hu et al and Qian et al pooled the progression‐free survival (PFS) and overall response rate (ORR) from 13 clinical trials of NSCLC patients undergoing different lines of treatments with crizotinib.…”

“…These authors also included ORR, PFS, 1‐year overall survival (OS), complete response, partial response, stable disease, and dose reduction in crizotinib‐treated NSCLC patients from six clinical trials in the meta‐analyses to evaluate the efficacy and safety of crizotinib . Fan et al not only pooled the efficacy and safety parameters to evaluate alectinib but also included the intracranial ORR. Li et al reported better outcomes regarding OS, PFS, and ORR in a meta‐analysis of the overall therapeutic outcomes of ALKi.…”

ALK inhibitors for non-small cell lung cancer: A systematic review and network meta-analysis

“…[4] Previous systematic reviews of ALK inhibitors for the treatment of NSCLC have reported improved overall and progression-free survival with crizotinib and alectinib compared with chemotherapy. [6,7] However, previous reviews were limited by the use of a pair-wise metaanalysis approach, which permits comparison of only two therapies at one time (e.g., alectinib v. chemotherapy). When choosing between treatment options, clinicians require information about the relative effectiveness and safety of all available options.…”