Safety
intercurrent infectious disease, fatigue, seizure, hyponatremia, vomiting, anemia, rash, pyrexia, hemorrhage, tumor hemorrhage, decreased appetite, TRAEs
RTI, CORONAVIRUS DISEASE 2019, EVENT, HYPONATREMIA, ANEMIA, HEMORRHAGE, ADVERSE EVENT, RESPIRATORY TRACT INFECTION, EVENTS
Among 137 patients (arms 1 and 2), 118 (86%) had been treated for at least 6 months and 67 (49%) for at least 1 year. All patients experienced at least one treatment-emergent adverse event (TEAE). The most common TEAEs at any grade occurring in ≥20% of patients were hair color changes (76%), anemia (59%) and elevated creatine phosphokinase (CPK) (58%) (Table TEAEs and TRAEs (safety analysis set, TEAEs, TRAEs and laboratory abnormalities in ≥20% of patients and all TRAEs grade ≥3 occurring in ≥1 patient are reported. Patients are counted only once per event and are shown in the worst CTCAE grade that was reported for each event they experienced. MedDRA version 23.1; CTCAE version 5.0. APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; COVID-19, coronavirus disease 2019; CSF, cerebrospinal fluid; GGT, gamma-glutamyl transferase; LDH, lactate dehydrogenase; RTI, respiratory tract infection; WBC, white blood cell.A decrease in growth velocity was observed in patients treated with tovorafenib. At cycle 13 (Serious TEAEs were reported for 45% of patients, the most common being pyrexia (most cases were confounded by intercurrent infectious disease), seizure and vomiting (each 5%). Serious TRAEs occurred in 15% of patients, the most common being tumor hemorrhage (3%), decreased appetite, hyponatremia and vomiting (each 2%). Two of four patients with serious tumor hemorrhage TRAEs had a history of intratumoral hemorrhage before initiating tovorafenib, and, in all four, the serious events of tumor hemorrhage resolved.Nine (7%) patients had TRAEs leading to tovorafenib discontinuation, the most common being tumor hemorrhage (three patients) and decrease in growth velocity (two patients). TRAEs leading to dose reduction were seen in 33 (24%) patients, the most common being maculopapular rash (4%) and decreased appetite (3%). TRAEs leading to dose interruption occurred in 50 (37%) patients, the most common being maculopapular rash (9%), vomiting, fatigue, increased alanine aminotransaminase (ALT) and elevated CPK (each 4%). The median duration of dose interruption due to any TEAE was 14 d, or two doses.