Table 5 Adverse drug reactions related to different initial afatinib dosages
Adverse events | All patients | Afatinib 30 mg daily | Afatinib 40 mg daily | P value |
|---|---|---|---|---|
Maximal grade of events |  |  |  | < 0.0001 |
 No | 8 (4%) | 2 (2%) | 6 (8%) |  |
 Grade 1 | 62 (35%) | 50 (49%) | 12 (16%) |  |
 Grade 2 | 78 (44%) | 43 (42%) | 35 (45%) |  |
 Grade 3 | 31 (17%) | 7 (7%) | 24 (31%) |  |
Presence of any moderate and severe (≥ grade 2) adverse events | 109 (61%) | 50 (49%) | 59 (77%) | 0.0002 |
Details of moderate and severe (≥ grade 2) adverse events | ||||
 Diarrhea | 49 (27%) | 13 (13%) | 36 (47%) | < 0.0001 |
 Stomatitis | 14 (8%) | 4 (4%) | 10 (13%) | 0.0253 |
 Paronychia | 50 (28%) | 29 (28%) | 21 (27%) | 0.8642 |
 Acne and/or skin rash | 61 (34%) | 17 (17%) | 44 (57%) | < 0.0001 |
 Dry skin | 9 (5%) | 1 (1%) | 8 (10%) | 0.0043 |
 Pruritus | 9 (5%) | 1 (1%) | 8 (10%) | 0.0043 |
 Adverse events involving skin a | 62 (35%) | 18 (18%) | 44 (57%) | < 0.0001 |
 Hepatitis | 4 (2%) | 1 (1%) | 3 (4%) | 0.1913 |
 Interstitial lung disease | 0 (0%) | 0 (0%) | 0 (0%) |  |
Presence of any severe (≥ grade 3) adverse events | 31 (17%) | 7 (7%) | 24 (31%) | < 0.0001 |
Details of severe (≥ grade 3) adverse events | ||||
 Diarrhea | 14 (8%) | 2 (2%) | 12 (16%) | 0.0008 |
 Stomatitis | 3 (2%) | 2 (2%) | 1 (1%) | 0.7326 |
 Paronychia | 6 (3%) | 2 (2%) | 4 (5%) | 0.2340 |
 Acne and/or skin rash | 11 (6%) | 0 (0%) | 11 (14%) | < 0.0001 |
 Dry skin | 0 (0%) | 0 (0%) | 0 (0%) |  |
 Pruritus | 1 (1%) | 0 (0%) | 1 (1%) | 0.2484 |
 Adverse events involving skin a | 11 (6%) | 0 (0%) | 11 (14%) | < 0.0001 |
 Hepatitis | 1 (1%) | 1 (1%) | 0 (0%) | 0.3836 |
 Interstitial lung disease | 0 (0%) | 0 (0%) | 0 (0%) |  |
Details of adverse events | ||||
 Diarrhea |  |  |  | < 0.0001 |
  No | 47 (26%) | 33 (32%) | 14 (18%) |  |
  Grade 1 | 83 (46%) | 56 (55%) | 27 (35%) |  |
  Grade 2 | 35 (20%) | 11 (11%) | 24 (31%) |  |
  Grade 3 | 14 (8%) | 2 (2%) | 12 (16%) |  |
 Stomatitis |  |  |  | 0.0214 |
  No | 125 (70%) | 70 (69%) | 55 (71%) |  |
  Grade 1 | 40 (22%) | 28 (27%) | 12 (16%) |  |
  Grade 2 | 11 (6%) | 2 (2%) | 9 (12%) |  |
  Grade 3 | 3 (2%) | 2 (2%) | 1 (1%) |  |
 Paronychia |  |  |  | 0.6304 |
  No | 87 (49%) | 49 (48%) | 38 (49%) |  |
  Grade 1 | 42 (23%) | 24 (24%) | 18 (23%) |  |
  Grade 2 | 44 (25%) | 27 (26%) | 17 (22%) |  |
  Grade 3 | 6 (3%) | 2 (2%) | 4 (5%) |  |
 Acne and/or skin rash |  |  |  | < 0.0001 |
  No | 34 (19%) | 22 (22%) | 12 (16%) |  |
  Grade 1 | 84 (47%) | 63 (62%) | 21 (27%) |  |
  Grade 2 | 50 (28%) | 17 (17%) | 33 (43%) |  |
  Grade 3 | 11 (6%) | 0 (0%) | 11 (14%) |  |
 Dry skin |  |  |  | 0.0171 |
  No | 69 (39%) | 41 (40%) | 28 (36%) |  |
  Grade 1 | 101 (56%) | 60 (59%) | 41 (53%) |  |
  Grade 2 | 9 (5%) | 1 (1%) | 8 (10%) |  |
 Pruritus |  |  |  | 0.0381 |
  No | 112 (63%) | 68 (67%) | 44 (57%) |  |
  Grade 1 | 58 (32%) | 33 (32%) | 25 (32%) |  |
  Grade 2 | 8 (4%) | 1 (1%) | 7 (9%) |  |
  Grade 3 | 1 (1%) | 0 (0%) | 1 (1%) |  |
 Adverse events involving skin a |  |  |  | < 0.0001 |
  No | 24 (13%) | 16 (16%) | 8 (10%) |  |
  Grade 1 | 93 (52%) | 68 (67%) | 25 (32%) |  |
  Grade 2 | 51 (28%) | 18 (18%) | 33 (43%) |  |
  Grade 3 | 11 (6%) | 0 (0%) | 11 (14%) |  |
 Hepatitis |  |  |  | 0.1382 |
  No | 172 (96%) | 100 (98%) | 72 (94%) |  |
  Grade 1 | 3 (2%) | 1 (1%) | 2 (3%) |  |
  Grade 2 | 3 (2%) | 0 (0%) | 3 (4%) |  |
  Grade 3 | 1 (1%) | 1 (1%) | 0 (0%) |  |
 Interstitial lung disease |  |  |  | 0.2166 |
  Grade 1 | 2 (1%) | 2 (2%) | 0 (0%) |  |