Table 5. Adverse events with targeted agents in pNEN patients at unadjusted cohort.
| Adverse events | Surufatinib, n=36, n (%) | Sunitinib, n=50, n (%) | Everolimus, n=27, n (%) | P value (any grade) | P value (grade ≥3) | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Any grade | Grade ≥3 | Any grade | Grade ≥3 | Any grade | Grade ≥3 | |||||
| Any AE | 31 (86.1) | 9 (25.0) | 39 (78.0) | 13 (26.0) | 20 (74.1) | 3 (11.1) | 0.46 | 0.28 | ||
| Hypertension | 6 (16.7) | 1 (2.8) | 9 (18.0) | 3 (6.0) | 0 | 0 | 0.03 | 0.56 | ||
| Proteinuria | 8 (22.2) | 0 | 6 (12.0) | 0 | 0 | 0 | 0.01 | NA | ||
| WBC decreased | 2 (5.6) | 0 | 17 (34.0) | 0 | 2 (7.4) | 0 | <0.001 | NA | ||
| Neutrophil decreased | 1 (2.8) | 0 | 15 (30.0) | 6 (12.0) | 1 (3.7) | 0 | <0.001 | 0.01 | ||
| Febrile neutropenia | 0 | 0 | 1 (2.0) | 1 (2.0) | 0 | 0 | >0.99 | >0.99 | ||
| LYM decreased | 5 (13.9) | 0 | 2 (4.0) | 0 | 4 (14.8) | 0 | 0.16 | NA | ||
| Anemia | 4 (11.1) | 2 (5.6) | 11 (22.0) | 0 | 8 (29.6) | 0 | 0.18 | 0.15 | ||
| PLT decreased | 4 (11.1) | 0 | 19 (38.0) | 1 (2.0) | 2 (7.4) | 0 | 0.001 | >0.99 | ||
| Hemorrhage | 2 (5.6) | 1 (2.8) | 2 (4.0) | 1 (2.0) | 1 (3.7) | 0 | >0.99 | >0.99 | ||
| Occult blood positive | 5 (13.9) | 0 | 1 (2.0) | 0 | 0 | 0 | 0.02 | NA | ||
| AST increased | 4 (11.1) | 2 (5.6) | 4 (8.0) | 0 | 7 (25.9) | 1 (3.7) | 0.09 | 0.17 | ||
| ALT increased | 3 (8.3) | 1 (2.8) | 6 (12.0) | 0 | 7 (25.9) | 1 (3.7) | 0.11 | 0.30 | ||
| ALP increased | 5 (13.9) | 0 | 2 (4.0) | 0 | 3 (11.1) | 0 | 0.26 | NA | ||
| GGT increased | 3 (8.3) | 0 | 1 (2.0) | 0 | 7 (25.9) | 2 (7.4) | 0.003 | 0.055 | ||
| LDH increased | 4 (11.1) | 0 | 3 (6.0) | 0 | 4 (14.8) | 0 | 0.36 | NA | ||
| Bilirubin increased | 11 (30.6) | 2 (5.6) | 3 (6.0) | 0 | 2 (7.4) | 0 | 0.003 | 0.15 | ||
| Hypoalbuminemia | 4 (11.1) | 0 | 6 (12.0) | 0 | 5 (18.5) | 0 | 0.72 | NA | ||
| Edema | 0 | 0 | 5 (10.0) | 0 | 1 (3.7) | 0 | 0.08 | NA | ||
| Creatinine increased | 3 (8.3) | 0 | 4 (8.0) | 0 | 1 (3.7) | 0 | 0.80 | NA | ||
| Hyperuricemia | 6 (16.7) | 0 | 1 (2.0) | 0 | 1 (3.7) | 0 | 0.02 | NA | ||
| Hyperlipemia | 4 (11.1) | 1 (2.8) | 0 | 0 | 7 (25.9) | 0 | <0.001 | 0.55 | ||
| Hyperglycemia | 7 (19.4) | 0 | 0 | 0 | 8 (29.6) | 0 | <0.001 | NA | ||
| Hypoglycemia | 1 (2.8) | 0 | 1 (2.0) | 0 | 0 | 0 | >0.99 | NA | ||
| TSH increased | 6 (16.7) | 0 | 1 (2.0) | 0 | 0 | 0 | 0.006 | NA | ||
| Hypothyroidism | 3 (8.3) | 0 | 0 | 0 | 0 | 0 | 0.03 | NA | ||
| Nausea/vomiting | 2 (5.6) | 0 | 0 | 0 | 1 (3.7) | 0 | 0.17 | NA | ||
| Diarrhea | 6 (16.7) | 0 | 1 (2.0) | 0 | 1 (3.7) | 0 | 0.02 | NA | ||
| Abdominal discomfort | 1 (2.8) | 0 | 1 (2.0) | 0 | 0 | 0 | >0.99 | NA | ||
| Stomatitis | 0 | 0 | 3 (6.0) | 0 | 7 (25.9) | 0 | <0.001 | NA | ||
| Muscle pain | 0 | 0 | 0 | 0 | 0 | 0 | NA | NA | ||
| Fatigue | 0 | 0 | 2 (4.0) | 0 | 0 | 0 | 0.50 | NA | ||
| HFS reaction | 1 (2.8) | 0 | 5 (10.0) | 2 (4.0) | 0 | 0 | 0.16 | 0.50 | ||
| Cough | 0 | 0 | 0 | 0 | 1 (3.7) | 0 | 0.23 | NA | ||
| Interstitial pneumonia | 0 | 0 | 0 | 0 | 1 (3.7) | 0 | 0.23 | NA | ||
| Infection | 1 (2.8) | 0 | 1 (2.0) | 1 (2.0) | 3 (11.1) | 1 (3.7) | 0.15 | 0.71 | ||
| Cardiac toxicity | 1 (2.8) | 0 | 0 | 0 | 1 (3.7) | 0 | 0.30 | NA | ||
AE, adverse event; pNEN, pancreatic 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.