Table 6. Adverse events with targeted agents in epNEN patients at unadjusted cohort.
| Adverse events | Surufatinib, n=87, n (%) | Everolimus, n=41, n (%) | P value (any grade) | P value (grade ≥3) | |||
|---|---|---|---|---|---|---|---|
| Any grade | Grade ≥3 | Any grade | Grade ≥3 | ||||
| Any AE | 73 (83.9) | 27 (31.0) | 32 (78.0) | 7 (17.1) | 0.42 | 0.09 | |
| Hypertension | 30 (34.5) | 14 (16.1) | 0 | 0 | <0.001 | 0.005 | |
| Proteinuria | 33 (37.9) | 2 (2.3) | 1 (2.4) | 0 | <0.001 | >0.99 | |
| WBC decreased | 7 (8.0) | 2 (2.3) | 4 (9.8) | 0 | 0.74 | >0.99 | |
| Neutrophil decreased | 3 (3.4) | 1 (1.1) | 3 (7.3) | 2 (4.9) | 0.38 | 0.24 | |
| Febrile neutropenia | 0 | 0 | 1 (2.4) | 1 (2.4) | 0.32 | 0.32 | |
| LYM decreased | 12 (13.8) | 2 (2.3) | 7 (17.1) | 0 | 0.62 | >0.99 | |
| Anemia | 15 (17.2) | 3 (3.4) | 15 (36.6) | 3 (7.3) | 0.01 | 0.38 | |
| PLT decreased | 6 (6.9) | 3 (3.4) | 4 (9.8) | 0 | 0.72 | 0.55 | |
| Hemorrhage | 6 (6.9) | 1 (1.1) | 1 (2.4) | 0 | 0.42 | >0.99 | |
| Occult blood positive | 5 (5.7) | 0 | 0 | 0 | 0.17 | NA | |
| AST increased | 16 (18.4) | 2 (2.3) | 7 (17.1) | 1 (2.4) | 0.85 | >0.99 | |
| ALT increased | 9 (10.3) | 2 (2.3) | 4 (9.8) | 0 | >0.99 | >0.99 | |
| ALP increased | 4 (4.6) | 1 (1.1) | 5 (12.2) | 0 | 0.14 | >0.99 | |
| GGT increased | 8 (9.2) | 3 (3.4) | 7 (17.1) | 1 (2.4) | 0.24 | >0.99 | |
| LDH increased | 18 (20.7) | 0 | 9 (22.0) | 0 | 0.87 | NA | |
| Bilirubin increased | 17 (19.5) | 3 (3.4) | 1 (2.4) | 0 | 0.009 | 0.55 | |
| Hypoalbuminemia | 12 (13.8) | 0 | 5 (12.2) | 0 | 0.80 | NA | |
| Edema | 1 (1.1) | 0 | 0 | 0 | >0.99 | NA | |
| Creatinine increased | 9 (10.3) | 0 | 2 (4.9) | 1 (2.4) | 0.50 | 0.32 | |
| Hyperuricemia | 18 (20.7) | 1 (1.1) | 1 (2.4) | 0 | 0.007 | >0.99 | |
| Hyperlipemia | 7 (8.0) | 0 | 10 (24.4) | 0 | 0.01 | NA | |
| Hyperglycemia | 8 (9.2) | 0 | 15 (36.6) | 0 | <0.001 | NA | |
| Hypoglycemia | 3 (3.4) | 0 | 0 | 0 | 0.55 | NA | |
| TSH increased | 22 (25.3) | 0 | 0 | 0 | <0.001 | NA | |
| Hypothyroidism | 3 (3.4) | 0 | 0 | 0 | 0.55 | NA | |
| Nausea/vomiting | 2 (2.3) | 0 | 1 (2.4) | 0 | >0.99 | NA | |
| Diarrhea | 13 (14.9) | 0 | 2 (4.9) | 0 | 0.14 | NA | |
| Abdominal discomfort | 1 (1.1) | 0 | 0 | 0 | >0.99 | NA | |
| Stomatitis | 0 | 0 | 9 (22.0) | 1 (2.4) | <0.001 | 0.32 | |
| Muscle pain | 1 (1.1) | 0 | 0 | 0 | >0.99 | NA | |
| Fatigue | 6 (6.9) | 0 | 2 (4.9) | 0 | >0.99 | NA | |
| HFS reaction | 1 (1.1) | 0 | 2 (4.9) | 0 | 0.24 | NA | |
| Cough | 0 | 0 | 1 (2.4) | 0 | 0.32 | NA | |
| Interstitial pneumonia | 0 | 0 | 4 (9.8) | 0 | 0.009 | NA | |
| Infection | 1 (1.1) | 0 | 2 (4.9) | 0 | 0.24 | NA | |
| Cardiac toxicity | 1 (1.1) | 0 | 2 (4.9) | 0 | 0.24 | NA | |
AE, adverse event; epNEN, extrapancreatic neuroendocrine neoplasm; WBC, white blood cell; LYM, lymphocyte; PLT, platelet; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; GGT, γ-glutamyl transferase; LDH, lactate dehydrogenase; TSH, thyroid-stimulating hormone; HFS, hand-foot skin syndrome; NA, not available.