Exposure-adjusted incidence rates of adverse events with SCEMBLIX and bosutinib4
Limitation: Exposure-adjusted incidence rate (EAIR) analysis is utilized when there is a difference in exposure between 2 arms or 2 studies. The exposure-adjusted rates assume the probability that an adverse event will happen is constant over time, which is not always true.
The median duration of exposure was 24 months (range: 0 to 46 months) for patients receiving SCEMBLIX and 7 months (range: 0 to 43 months) for patients receiving bosutinib.4
As a result of the higher treatment discontinuation rate in the bosutinib arm, the duration of exposure to SCEMBLIX and bosutinib differed. Incidence per 100 PTY is a measurement that compares the adverse event incidence rates between the 2 groups (268.9 PTY vs 72.9 with SCEMBLIX and bosutinib, respectively) while adjusting for this imbalance in duration.
Adverse events of special interest (AESIs) were the AEs that represent the group of AEs with specific interest when patients are being treated with study drug. These AEs were defined based on the class effects of other TKIs in the same class, mechanism of action, and the current preclinical and clinical knowledge of the study drug. The AESIs related to SCEMBLIX are: myelosuppression, pancreatic toxicity, hypersensitivity, hepatotoxicity, hepatitis B reactivation, reproductive toxicity, GI toxicity, phototoxicity, QTc prolongation, cardiac failure, edema and fluid retention, ischemic heart disease and CNS conditions, AOEs, and hemorrhage.
Dose reductions for SCEMBLIX: hypersensitivity 1 (0.6%). Dose reductions for bosutinib: edema and fluid retention 1 (1.3%); GI toxicity 10 (13.2%), hepatotoxicity 3 (3.9%); hypersensitivity 3 (3.9%).2
AEs, adverse events; AOEs, arterial occlusive events; CNS, central nervous system; EAIRs, exposure-adjusted incidence rates; GI, gastrointestinal; PTY, patient-treatment years.
jBased on the safety analysis set. Numbers represent counts of patients. Other adverse events of special interest, such as hepatitis B virus reaction, hepatotoxicity (clinical events), pancreatic toxicity (clinical events), and phototoxicity, were not reported.4
kAdverse events of special interest are reported as grouped adverse reactions.4
lGI toxicity includes diarrhea, nausea, abdominal pain, vomiting, constipation, noncardiac chest pain, abdominal pain upper, abdominal distension, abdominal pain lower, abdominal tenderness, epigastric discomfort, flatulence, and abdominal discomfort.2
mIncludes ARs related to laboratory value abnormalities.4
nIncludes the preferred terms rash, rash maculopapular, dermatitis acneiform, periorbital edema, rash pustular, rhinitis allergic, urticaria, allergic transfusion reaction, dermatitis, dermatitis allergic, dermatitis contact, dermatitis exfoliative generalized, eczema, rash morbilliform, drug eruption, erythema multiforme, eyelid edema, face edema, hand dermatitis, hypersensitivity, and rash erythematous.4
oIncluded 2 events of maternal exposure during pregnancy (with a spontaneous abortion reported in one case) with asciminib and 2 diagnoses (after informed consent) of congenital cardiovascular anomaly that were not resolved—1 each with asciminib and bosutinib.4