Table 2.
Adverse Events, According to Treatment Group.*
| Event | Group 1 (N=80) | Group 2 (N = 162) | Group 3 (N = 161) | P Value | |
|---|---|---|---|---|---|
| Group 2 vs. Group 1 | Group 3 vs. Group 1 | ||||
| Median duration of study-drug exposure — days | 104 | 252 | 336 | ||
| Death — no. (%) | 0 | 1 (<1) † | 0 | 0.99 | 0.99 |
| Any adverse event — no. (%) | 77 (96) | 160 (99) | 161 (100) | 0.34 | 0.04 |
| Discontinuation owing to adverse event — no. (%) | 2(2) | 13(8) | 20 (12) | 0.15 | 0.02 |
| Dose modification owing to adverse event — no. (%) | 11 (14) | 47 (29) | 53 (33) | 0.01 | 0.002 |
| Any life-threatening adverse event — no. (%) | 0 | 4(2) | 5(3) | 0.31 | 0.17 |
| Any serious adverse event — no. (%) | 4(5) | 16 (10) | 23 (14) | 0.23 | 0.03 |
| Hematologic event | |||||
| Reduced neutrophil count — no. (%) | |||||
| Grade 3: 500 to <750 per mm3 | 7(9) | 30 (19) | 32 (20) | 0.06 | 0.03 |
| Grade 4: <500 per mm3 | 3(4) | 10(6) | 11(7) | 0.55 | 0.40 |
| Mean change in hemoglobin from baseline — g/dl | |||||
| At wk 12 | −2.89 | −4.02 | −3.96 | <0.001 | <0.001 |
| At wk 24 | −2.69 | −4.36 | −4.31 | <0.001 | <0.001 |
| At wk 48 | −3.45 | −4.16 | −4.49 | 0.09 | 0.005 |
| Hemoglobin level — no. (%) | |||||
| Grade 2: 8.0 to <9.5 g/dl | 9(11) | 42 (26) | 41 (25) | 0.01 | 0.01 |
| Grade 3: 6.5 to <8.0 g/dl | 1(1) | 5(3) | 12 (7) | 0.67 | 0.07 |
| Grade 4: <6.5 g/dl | 0 | 0 | 1(<1) | 0.99 | 0.99 |
| Erythropoietin use | 17 (21) | 66 (41) | 74 (46) | 0.003 | <0.001 |
| Transfusion | 0 | 3(2) | 14(9) | 0.55 | 0.006 |
| Common adverse event — no. (%)‡ | |||||
| Anemia | 16 (20) | 70 (43) | 74 (46) | <0.001 | <0.001 |
| Dry skin | 6 (8) | 34 (21) | 36 (22) | 0.009 | 0.004 |
| Dysgeusia | 9 (11) | 69 (43) | 72 (45) | <0.001 | <0.001 |
| Rash | 4 (5) | 27 (17) | 22 (14) | 0.01 | 0.05 |
A listing of all life-threatening and serious adverse events can be found in Table S4 in the Supplementary Appendix. The P values presented are nominal, have not been adjusted for multiple comparisons, and are based on Fisher’s exact test for categorical variables and Student’s t-test for continuous variables.
There was one death by suicide in group 2, which occurred 18 weeks after the end of the study treatment and was considered to be unrelated to the study treatment.
Common adverse events were those classified as being related to a study treatment and occurring with an incidence of 15% or more in any group. Only common adverse events for which P<0.05 for a pairwise comparison with group 1 (group 3 vs. group 1 or group 2 vs. group 1) are shown. All other common adverse events (for which the treatment-related incidence was 15% or more in any group) can be found in Table S5 in the Supplementary Appendix.