The most common grade 3 and 4 adverse events were hepatotoxicity ( 188 [ 8 % ] ) , hypertension ( 99 [ 4 % ] ) , cardiac disorders ( 52 [ 2 % ] ) , osteoporosis ( 31 [ 1 % ] ) , hypokalaemia ( 28 [ 1 % ] ) , and fluid retention or oedema ( 23 [ 1 % ] ) .