The efficacy and safety of selumetinib as secondary therapy for late-stage and metastatic non-small cell lung cancer: results from a systematic review and meta-analysis

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common subtype of all lung cancers, and KRAS is the most common mutation in this population. Unfortunately, this subgroup remains “undruggable” with the lack of an approved targeted therapy. Selumetinib has been investigated as a secondary therapy in several trials and compared to various drug regimens. Therefore, we conducted this systematic review and network meta-analysis to determine the comparative effectiveness of this drug as compared to others in patients with late-stage and malignant NSCLC. METHODS: Up to July 1, 2020, 9 databases (PubMed, Scopus, Web of Science, mRCT, ICTRP, clinicaltrials.gov, VHL, SIGLE, and Google Scholar) were searched for studies following the PICOS framework: randomized trials reporting the efficacy (rate of disease progression/lack of response) of selumetinib compared to other therapies in patients with late-stage/metastatic NSCLC. The quality of retrieved studies were assessed with the revised Cochrane risk-of-bias tool. Frequentist network meta-analysis was conducted to estimate the efficacy of selumetinib as compared to other therapies and/or placebo. RESULTS: Out of the 163 articles yielded from the primary search, 9 studies (1,195 patients) were finally included in our systematic review. The majority of clinical cases had a performance status (PS) of 0–2, and the mean age was 62 years. The overall efficacy of selumetinib was 71.77% (95% CI: 63.24–81.45%), with selumetinib administered alone having better efficacy compared to combined therapy (65.20% vs. 74.08%). In the network analysis, selumetinib had higher efficacy compared to chemo- or immune therapy, but not significantly so. The overall SAE rate of selumetinib was 42.96% (95% CI: 34.74–53.13%), with selumetinib having a significantly better safety profile compared to combined therapy (10.49% vs. 47.38%). In the network analysis, the placebo had the best safety profile followed by selumetinib and chemo- and immune therapy. Five studies had high risk of bias, 2 had some concerns, and 2 had low risk of bias. DISCUSSION: The efficacy of selumetinib is not superior compared to combined therapy for treating NSCLC but does have a better safety profile. Current evidence is still limited, and more robust trials are still required.