Table VI.
AEs with ALK-TKIs across pivotal phase III clinical trials on advanced NSCLC.
| Study (n)a, (Ref.) | Timeb | Common AEs (number and percentage of all grades) | Common grade ≥3AEs (number and percentage) | Dose change related to AEs |
|---|---|---|---|---|
| PROFILE 1007 | February 2012 | Vision disorder (103; 60%) | Elevated aminotransferase levels (27; 16%) | – |
| (n=173), (34) | Diarrhea (103; 60%) | Dyspnea (7; 13%) | ||
| Nausea (94; 55%) | Constipation (4; 2%) | |||
| Vomiting (80; 47%) | Fatigue (4; 2%) | |||
| PROFILE 1014 | January 20, 2011 | Vision disorder (122; 71%) | Elevated aminotransferases (24; 14%) | – |
| (n=171), (35) | Diarrhea (105; 61%) | Neutropenia (19; 11%) | ||
| Vomiting (78; 46%) | Dyspnea (5; 3%) | |||
| Constipation (74; 43%) | Fatigue (5; 3%) | |||
| PROFILE 1029 | September 2012 | Increased transaminase level (72; 69.2%) | Neutropenia (17; 16.3%) | – |
| (n=104), (61) | Diarrhea (61; 58.7%) | Increased transaminase level (12; 11.5%) | ||
| Vision disorder (58; 55.8%) | Leukopenia (3; 2.9%) | |||
| Vomiting (55; 52.9%) | Anemia (3; 2.9%) | |||
| ASCEND-4 | Aug 19, 2013 | Diarrhea (160; 85%) | Alanine aminotransferase increased (58; 31%) | Dose adjustment or |
| (n=189), (43) | Nausea (130; 69%) | Gamma-glutamyltransferase increased (54; 29%) | interruption were reported in | |
| Vomiting (125; 66%) | Aspartate aminotransferase increased (32; 17%) | 152 (80%) | ||
| Alanine aminotransferase increased (114; 60%) | Blood alkaline phosphatase increased (14; 7%) | |||
| ASCEND-5 | June 28, 2013 | Diarrhea (78; 68%) | ALT concentration increased (22; 19%) | Dose adjustment or interruption or |
| (n=115), (44) | Nausea (67; 58) | GGT concentration increased (21; 18%) | delay were reported in 92 (80%) | |
| Vomiting (51; 44%) | AST concentration increased (15; 13%) | |||
| ALT concentration increased (25; 22%) | Vomiting (9; 8%) | |||
| Nausea (9; 8%) | ||||
| ALUR | – | Fatigue (4; 4.7) | Asthenia (2; 2.9%) | Dose adjustment or interruption in |
| (n=72), (47) | Constipation (13; 18.6%) | Pneumonia (2; 2.9%) | 20 (28.6%) | |
| Neutropenia (2; 2.9%) | Syncope (2; 2.9%) | |||
| Diarrhea (2; 2.9%) | Acute kidney injury (2; 2.9%) | |||
| Dyspnea (6; 8.6%) | ||||
| J-ALEX | Nov 18, 2013 | Constipation (36; 35%) | Blood creatine phosphokinase increase (5; 5%) | Dose adjustment or interruption in |
| (n=103), (48) | Nasopharyngitis (21; 20%) | Respiratory, thoracic, mediastinal disorders and | 39 (38%) | |
| Blood creatine phosphokinase increased (18; 17%) | interstitial lung disease (5; 5%) | |||
| Dysgeusia (19; 18%) | Maculopapular rash (3; 3%) | |||
| Neutrophil count decrease (2; 2%) | ||||
| Electrocardiogram QT prolonged (2; 2%) | ||||
| ALEX | August 18, 2014 | Anemia (30; 20%) | Blood bilirubin increased (3; 2%) | Dose adjustment or interruption |
| (n=152), (49) | Peripheral edema (26; 17%) | Anemia (7; 5%) | 70 (46%) | |
| Myalgia (24; 16%) | ALT increased (7; 5%) | |||
| Blood bilirubin increased (23; 15%) | AST increased (8; 5%) | |||
| ALTA-1L | April 2016 | Diarrhea (67; 49%) | Increased blood creatine kinase level (22; 16%) | Dose adjustment in 12% |
| (n=136), (53) | Increased blood creatine kinase level (53; 39%) | Increased lipase level (18; 13%) | ||
| Nausea (36; 26%) | Hypertension (13; 10%) | |||
| Cough (34; 25%) | Increased amylase level (7; 5%) |
a
The number of patients in the treatment group.
b
Subject to time of first posted for clinical trial. Common AEs define the top four AEs, unless there are multiple rankings in the fourth. ALK-TKIs, anaplastic lymphoma kinase tyrosine kinase inhibitors; NSCLC, non-small-cell lung cancer; AEs, adverse events; ALT, alanine transaminase; AST, aspartate transaminase; QT, the time between the start of the Q-wave and the end of the T-wave; GGT, gamma-glutamyl transpeptidase.