Introduction
Current treatment options
Angiogenesis and ovarian cancer
Search strategy
Bevacizumab in advanced ovarian cancer
Phase II trial data
Phase III trial data
Study (n) | Regimen | ORR (CR + PR), % | Median PFS, months | Median OS, months |
---|---|---|---|---|
[p value] | [HR; p value] | [HR; p value] | ||
GOG-0218 [21] | CP + placebo vs. CP + Bev vs. CP + Bev → Bev maintenance | – | 10.3 vs. 11.2 vs. 14.1 | 39.3 vs. 38.7 vs. 39.7 |
(n = 1,873) | [0.908; 0.16]a | [1.036; 0.76]a | ||
[0.717; < 0.001]b | [0.915; 0.45]b | |||
CP vs. CP + Bev → Bev maintenance | 48 vs. 67 | 17.4 vs. 19.8 | Restricted mean survival time, months | |
(n = 1,528) | [< 0.001] | [0.87; 0.04] | 44.6 vs. 44.5 | |
CG + placebo vs. CG + Bev | 57.4 vs. 78.5 | 8.4 vs. 12.4 | 33.7c vs. 33.4c | |
(n = 484) | [< 0.0001] | [0.484; < 0.0001] | [0.960; 0.736] | |
CTx (PLD, P or Top) vs. CTx + Bev | 12.6 vs. 30.9 | 3.4 vs. 6.7 | 13.3 vs. 16.6 | |
(n = 361) | [0.001] | [0.48; < 0.001] | [0.85; 0.174] |
GOG-0218
ICON7
OCEANS
AURELIA
Biomarker analyses
Safety of bevacizumab in advanced ovarian cancer
Grade ≥ 3 AE, % | GOG-0218[21] | ICON7[22] | OCEANS[41] | AURELIA[26] | |||||
---|---|---|---|---|---|---|---|---|---|
CP + placebo | CP + Bev | CP + Bev → Bev | CP | CP + Bev → Bev | CG + placebo | CG + Bev | CTx | CTx + Bev | |
(n = 601) | (n = 607) | (n = 608) | (n = 753) | (n = 745) | (n = 233) | (n = 247) | (n = 182) | (n = 179) | |
Neutropenia
| 57.7a | 63.3a | 63.3a | 15 | 17 | – | – | – | – |
Pain
| 41.6b | 41.5b | 47.0b | – | – | – | – | – | – |
Thrombocytopenia
| – | – | – | 2 | 3 | 34 | 40 | – | – |
Hypertension
| 7.2b | 16.5b | 22.9b | <1 | 6 | 0.4 | 17.8 | – | – |
VTE
| 5.8c | 5.3c | 6.7c | 2 | 4 | – | – | 4 | 3 |
Febrile neutropenia
| 3.5c | 4.9c | 4.3c | 2 | 3 | – | – | 1 | 1 |
Proteinuria
| 0.7 | 0.7 | 1.6 | <1 | 1 | 0.9 | 9.7 | – | – |
Bleeding (non-CNS)
| 0.8 | 1.3 | 2.1 | <1 | 1 | 0.9 | 5.7 | 1 | 1 |
Wound healing complications
| 2.8c | 3.6c | 3.0c | <1 | 1 | – | – | – | – |
ATE
| 0.8c | 0.7c | 0.7c | 1 | 3 | – | – | 0 | 2 |
GI events
| 1.2b | 2.8b | 2.6b | <1 | 1 | 0 | 0 | – | – |
Epistaxis
| – | – | – | – | – | 0.4 | 4.9 | – | – |
Abscess/fistula
| – | – | – | 1 | 1 | 0.4c | 1.6c | – | – |
RPLS
| 0 | 0.2c | 0.2c | 0 | 0 | 0 | 0.8c | 0 | 1 |
CHF
| – | – | – | <1 | <1 | – | – | 1 | 1 |
CNS bleeding
| 0 | 0 | 0.3c | 0 | <1 | – | – | – | – |
Emerging anti-angiogenic agents in ovarian cancer
Study (n) | Regimen | ORR (CR + PR), % | Median PFS, months | Median OS, months |
---|---|---|---|---|
Matulonis et al. [42] | Cediranib 45 mg/day | 17 | 5.2 | Not reached |
(n = 46) | ||||
Ledermann et al. [43] | Cediranib 20 mg/day → cedarinib maintenance vs. placebo | – | Restricted mean survival time, months | Restricted mean survival time, months |
(n = 456) | 11.4 vs. 9.4 | 20.3 vs. 17.6 | ||
Du Bois et al. [44] | Pazopanib 800 mg/day vs. placebo | – | 17.9 vs. 12.3 | Not reached |
(n = 940) | ||||
Campos et al. [45] | Sunitinib 37.5 mg/day | 8.3 | 9.9b | – |
(n = 35) | ||||
Biagi et al. [46] | Sunitinib 50 mg/day (int.) | 13.3 | 4.1 | – |
(n = 30) | ||||
Baumann et al. [47] | Sunitinib 50 mg/day (int.) vs. 37.5 mg/day (cont.) | 16.7 vs. 5.4 | 4.8 vs. 2.9 | 13.6 vs. 13.7 |
(n = 73) | ||||
Matei et al. [48] | Sorafenib 400 mg b.i.d. | 3.4 | 6-month PFS rate: 24% | – |
(n = 71) | ||||
Herzog et al. [49] | Sorafenib 400 mg b.i.d. vs. placebo | – | 386 vs. 478a | – |
(n = 249) | ||||
Ledermann et al. [50] | Nintedanib 250 mg b.i.d. vs. placebo | – | 36-week PFS rate: | – |
(n = 83) | 16.3% vs. 5.0% | |||
Du Bois et al. [51] | Nintedanib 200 mg b.i.d. + CP vs. nintedanib + placebo | – | 17.3 vs. 16.6 | – |
(n = 1,366) | ||||
Coleman et al. [52] | Aflibercept 6 mg/kg + D | 54 | 6.2 | 24.3 |
(n = 46) | ||||
Gotlieb et al. [53] | Aflibercept 4 mg/kg vs. placebo | – | 6.3 vs. 7.3b | 12.9 vs. 16.0b |
(n = 55) | ||||
Colombo et al. [54] | Aflibercept 4 mg/kg | – | 8.5b | – |
(n = 16) | ||||
Karlan et al. [55] | Trebananib 10 mg/kg + P vs. trebananib 3 mg/kg + P vs. placebo + P | 37 vs. 19 vs. 27 | 7.2 vs. 5.7 vs. 4.6 | 22.5 vs. 20.4 vs. 20.9 |
(n = 161) | ||||
Monk et al. [56] | Trebananib 15 mg/kg + P vs. placebo + P | 38 vs. 30 | 7.2 vs. 5.4 | 19.0c vs. 17.3c |
(n = 919) |