Evaluation of Lung Toxicity Related to the Treatment With Alectinib Using a Pharmacovigilance Database

The anaplastic lymphoma kinase (ALK) inhibitor alectinib is recommended as a first-line treatment for ALK lung cancer. Interstitial lung disease is the most common adverse event leading to discontinuation of alectinib. The purpose of this study was to use the Japanese Adverse Drug Event Report database for the evaluation of incidence trends and timing of alectinib toxicity in the lungs.

Adverse drug reactions (ADRs) by alectinib were extracted between April 2004 and March 2021. Data related to lung toxicity ADRs were analyzed, and the relative risk was estimated using the reporting odds ratio (ROR) and 95% confidence interval (CI). The time of onset of the lung toxicity signs was noted.

We obtained 524 reports of ADRs associated with alectinib. Of these, 157 were lung toxicity, including interstitial lung disease, lung disorder, pneumonitis, and pulmonary edema. The RORs for these signs were 10.28 (95%CI=8.38-12.60), 9.19 (5.58-15.13), 7.40 (3.67-14.88), and 7.01 (3.13-15.69), respectively. The median onset times (quartiles, 25-75%) of interstitial lung disease, lung disorder, pneumonitis, and pulmonary edema associated with alectinib treatment were 92 (36-195), 57 (51-129), 228 (62-431), and 83 (22-96) days, respectively.

Among the lung toxicity signs, interstitial lung disease had the highest ROR, suggesting a strong causal relationship with alectinib treatment. Interstitial lung disease most frequently developed within 60 days after the start of treatment. These results will be useful for monitoring adverse events associated with the use of alectinib.