Table 3.

Main grade 3 or higher adverse events

Study	Main grade 3 or higher adverse events (over 10%)
Jänne et al. [43]	Neutropenia (67%), febrile neutropenia (18%), dyspnea (2%), and asthenia (9%)
Gandara et al. [46]	Trametinib + docetaxel: anemia (16%), asthenia (4%), diarrhea (10%), dyspnea (4%), fatigue (10%), hypoalbuminemia (4%), mucosal (4%), neutropenia (22%), and stomatitis (4%). Trametinib + pemetrexed: anemia (13%), AST increased (4%), asthenia (9%), decreased appetite (4%), diarrhea (4%), dyspnea (7%), hyponatremia (15%), nausea (7%), and neutropenia (20%)
Jänne et al. [47]	Diarrhea (6%), rash (3%), nausea (1%), fatigue (2%), stomatitis (3%), edema peripheral (1%), vomiting (2%), asthenia (5%), decreased appetite (1%), dermatitis acneiform (2%), neutropenia (6%), anemia (1%) and dyspnea (2%)
Greystoke et al. [50]	Neutropenia (26%), anemia (22%), and thrombocytopenia (20%)
Seto et al. [51]	Selumetinib monotherapy: blood and lymphatic system disorders (6%), neutropenia (6%), investigations (18%), AST increase (6%), GGT increase (6%), WBC count decrease (6%), infections and infestations (6%), pneumonia (6%), gastrointestinal disorders (12%), diarrhea (6%), vomiting (6%), respiratory, thoracic and mediastinal disorders (12%), interstitial lung disease (6%), metabolism and nutrition disorders (6%) and hypoalbuminemia (6%)