Safety
nausea, death, neutropenia, diarrhea, hypoxia, vomiting, anemia, dehydration, small-intestinal obstruction, bacterial pneumonia, acute kidney injury, necrotizing soft-tissue infection, hypokalemia
PULMONARY EMBOLISM, DISEASE PROGRESSION, NEUTROPENIA, DEEP VEIN THROMBOSIS, ADVERSE EVENT, THROMBOCYTOPENIA, HYPOXIA, EVENTS, ANEMIA, DEHYDRATION, BACTERIAL PNEUMONIA, PANCREATIC CANCER, PANCREATITIS, PORTAL VEIN THROMBOSIS
Causally related AEs (stratified by any grade and grade ≥ 3) are shown in Supplementary Table 2 for patients who received only adavosertib and patients who received both adavosertib and the probe cocktail. Four of 33 (12.1%) patients experienced AEs with cocktail alone, compared with 16/26 (61.5%) patients who received probe cocktail plus adavosertib and 16/30 (53.3%) patients after receiving adavosertib alone on days 1 and 2. Treatment-related AEs were reported by 12/26 (46.2%) patients receiving probe cocktail plus adavosertib and 11/30 (36.7%) patients after receiving adavosertib alone on days 1 and 2. The most common treatment-related AEs in patients receiving probe cocktail plus adavosertib (Adverse events of CTCAE grade ≥ 3 were observed in: 4/26 (15.4%) patients receiving probe cocktail plus adavosertib (anemia, neutropenia, pulmonary embolism, and portal vein thrombosis in one [3.8%] patient each); 5/30 (16.7%) patients receiving adavosertib alone on days 1 and 2 (diarrhea in three [10.0%] patients, necrotizing soft-tissue infection, neutropenia, thrombocytopenia, dehydration, hypokalemia, hypoxia, nausea, pancreatitis, small-intestinal obstruction, vomiting, and acute kidney injury in one [3.3%] patient each [multiple events were experienced by the same five (16.7%) patients]); and 0/33 patients receiving cocktail alone.One patient receiving adavosertib alone on days 1 and 2 reported two serious AEs (SAEs) considered related to adavosertib (acute kidney injury, which resolved after 2 days, and pancreatitis, which did not resolve during the study but improved to grade 2 after 2 days) that led to discontinuation; four patients reported five SAEs that were not considered related to treatment (grade 2 bacterial pneumonia and deep vein thrombosis, which did not resolve; grade 3 necrotizing soft-tissue infection, which resolved; grade 3 small-bowel obstruction, which did not resolve; and grade 4 pulmonary embolism, which resolved).Two patients discontinued treatment because of AEs: one as a result of grade 3 diarrhea considered related to adavosertib, which resolved, and the other for grade 3 small-bowel obstruction, which was not considered related to adavosertib and did not resolve.No AEs with an outcome of death were observed; one patient died as a result of disease progression (pancreatic cancer) following receipt of the probe cocktail but prior to receiving adavosertib.