Serum Albumin Affects the Time-to-treatment Failure of Alectinib: A Multicenter Retrospective Study

Background/aim: Alectinib is recommended for anaplastic lymphoma kinase fusion gene-positive non-small cell lung cancer. We have experienced early alectinib discontinuation due to disease progression and adverse effects in real world. Because alectinib has a high protein-binding rate of >99%, low serum albumin may increase the concentration of free drug and affect efficacy and adverse events. However, no association between serum albumin and the clinical impact of alectinib has been reported. The purpose of this study was to determine the effect of serum albumin on time-to-treatment failure (TTF) in alectinib. Patients and methods: Fifty-six patients who were admitted to four hospitals (National Hospital Organization Hokkaido Cancer Center, Sapporo Minami-Sanjo Hospital, KKR Sapporo Medical Center, Otaru General Hospital) between October 2014 and September 2020 were retrospectively evaluated to identify those treated with alectinib. Results: The multivariate analysis showed that the risk of discontinuation was significantly higher with serum albumin <3.6 g/dl compared to >= 3.6 g/dl at the start of alectinib administration (hazard ratio=3.00; 95% confidence interval=1.36-6.66; p<0.01). On Kaplan-Meier curves, TTF for serum albumin <3.6 was significantly shorter than that for >= 3.6. (median TTF: 12.1 months vs. not reach, p<0.01). Conclusion: To the best of our knowledge, this study is the first to report that serum albumin <3.6 g/dl at alectinib induction is associated with poor TTF. Low serum albumin is a poor prognostic factor in cancer patients. Thus, serum albumin levels must be measured before treatment.