Table 4.
Treatment-Emergent Adverse Events Based on Prior Sorafenib/Lenvatinib Treatment (Safety Population)
| Prior sorafenib only |
Prior lenvatinib only |
Prior lenvatinib and sorafenib |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cabozantinib n = 63 |
Placebo n = 33 |
Cabozantinib n = 68 |
Placebo n = 34 |
Cabozantinib n = 39 |
Placebo n = 21 |
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| Any grade | Grade 3/4 | Any grade | Grade 3/4 | Any grade | Grade 3/4 | Any grade | Grade 3/4 | Any grade | Grade 3/4 | Any grade | Grade 3/4 | |
| Any AE, n (%) | 62 (98) | 40 (63) | 27 (82) | 7 (21) | 65 (96) | 39 (57) | 31 (91) | 14 (41) | 39 (100) | 27 (69) | 17 (81) | 4 (19) |
| Diarrhea | 41 (65) | 6 (10) | 2 (6) | 0 | 43 (63) | 6 (9) | 0 | 0 | 21 (54) | 1 (3) | 1 (5) | 0 |
| Palmar–plantar erythrodysesthesia | 35 (56) | 6 (10) | 1 (3) | 0 | 29 (43) | 7 (10) | 0 | 0 | 16 (41) | 4 (10) | 0 | 0 |
| Alanine aminotransferase increased | 18 (29) | 0 | 1 (3) | 0 | 13 (19) | 0 | 1 (3) | 1 (3) | 12 (31) | 1 (3) | 0 | 0 |
| Aspartate aminotransferase increased | 17 (27) | 0 | 1 (3) | 0 | 15 (22) | 0 | 1 (3) | 0 | 10 (26) | 0 | 0 | 0 |
| Decreased appetite | 17 (27) | 0 | 4 (12) | 0 | 27 (40) | 3 (4) | 3 (9) | 0 | 9 (23) | 2 (5) | 4 (19) | 0 |
| Hypertension | 16 (25) | 7 (11) | 1 (3) | 0 | 21 (31) | 8 (12) | 2 (6) | 2 (6) | 17 (44) | 5 (13) | 0 | 0 |
| Hypocalcemia | 15 (24) | 6 (10) | 2 (6) | 1 (3) | 17 (25) | 3 (4) | 1 (3) | 1 (3) | 10 (26) | 4 (10) | 0 | 0 |
| Weight decreased | 15 (24) | 2 (3) | 0 | 0 | 17 (25) | 2 (3) | 0 | 0 | 5 (13) | 0 | 2 (10) | 0 |
| Nausea | 14 (22) | 1 (2) | 2 (6) | 0 | 23 (34) | 2 (3) | 0 | 0 | 11 (28) | 1 (3) | 0 | 0 |
| Stomatitis | 13 (21) | 2 (3) | 1 (3) | 0 | 9 (13) | 3 (4) | 0 | 0 | 8 (21) | 1 (3) | 1 (5) | 0 |
| Asthenia | 12 (19) | 1 (2) | 4 (12) | 0 | 12 (18) | 3 (4) | 5 (15) | 0 | 5 (13) | 0 | 3 (14) | 0 |
| Fatigue | 11 (17) | 2 (3) | 2 (6) | 0 | 24 (35) | 8 (12) | 4 (12) | 0 | 14 (36) | 5 (13) | 1 (5) | 0 |
| Anemia | 10 (16) | 1 (2) | 3 (9) | 0 | 10 (15) | 2 (3) | 3 (9) | 0 | 1 (3) | 0 | 4 (19) | 1 (5) |
| Mucosal inflammation | 10 (16) | 0 | 0 | 0 | 11 (16) | 1 (1) | 0 | 0 | 8 (21) | 2 (5) | 0 | 0 |
| Hypomagnesemia | 7 (11) | 1 (2) | 3 (9) | 0 | 17 (25) | 1 (1) | 0 | 0 | 4 (10) | 0 | 0 | 0 |
| Vomiting | 7 (11) | 0 | 3 (9) | 0 | 18 (26) | 1 (1) | 2 (6) | 0 | 6 (15) | 2 (5) | 2 (10) | 0 |
| Dyspnea | 6 (10) | 0 | 1 (3) | 0 | 10 (15) | 2 (3) | 6 (18) | 1 (3) | 7 (18) | 1 (3) | 9 (43) | 2 (10) |
| Cough | 5 (8) | 0 | 7 (21) | 0 | 6 (9) | 0 | 8 (24) | 0 | 5 (13) | 0 | 2 (10) | 0 |
| Dysgeusia | 5 (8) | 0 | 0 | 0 | 14 (21) | 0 | 0 | 0 | 2 (5) | 0 | 0 | 0 |
| Proteinuria | 5 (8) | 3 (5) | 0 | 0 | 14 (21) | 0 | 2 (6) | 0 | 8 (21) | 1 (3) | 0 | 0 |
| Constipation | 3 (5) | 0 | 2 (6) | 0 | 12 (18) | 0 | 4 (12) | 0 | 6 (15) | 0 | 0 | 0 |
| Dysphonia | 3 (5) | 0 | 0 | 0 | 14 (21) | 0 | 0 | 0 | 3 (8) | 0 | 0 | 0 |
AEs, regardless of causality, were reported in >15% of patients in either treatment group. Severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.