Table 2.
Prospective Phase III clinical trials incorporating bevacizumab in the treatment of ovarian cancer indicating a progression-free survival advantage, but no overall survival advantage.
| Trial | n | Eligibility | Arms | Grade 3–4 AEs† | Primary end point |
Secondary end point | Ref. |
|---|---|---|---|---|---|---|---|
| GOG 218 | 1873 | Incompletely and completely‡ resected stage 3 or any stage 4; GOG PS 0–2 | iv. carboplatin (AUC 5) + iv. paclitaxel (175 mg/m2) + placebo followed by maintenance placebo Q3w iv. carboplatin (AUC 5) + iv. paclitaxel (175 mg/m2) + iv. bevacizumab (15 mg/kg) + placebo maintenance Q3w iv. carboplatin (AUC 5) + iv. Paclitaxel (175 mg/m2) + iv. bevacizumab (15 mg/kg) + iv. bevacizumab (15 mg/kg) maintenance Q3w | HTN; (22.9%); GI events (2.6%); proteinuria (1.6%); VTE (6.7%) | Median PFS; 10.3 vs 11.2 vs 14.1 months; HR: 0.717; (0.625–0.824); p < 0.001 | Median OS; 39.3 vs 38.7 vs 39.7 months; HR: 0.915 (0.727–1.15); p = 0.45 | [35] |
| ICON 7 | 1528 | Stage 1–2A (clear cell, grade 3); stage 2B-4; ECOG PS 0–2 | iv. carboplatin (AUC 5) + iv. paclitaxel (175 mg/m2) Q3w iv. carboplatin (AUC 5) + iv. paclitaxel (175 mg/m2) + iv. bevacizumab (7.5mg/kg) + iv. bevacizumab (7.5 mg/kg) maintenance Q3w | Bleeding (1%); HTN (6%); VTE (4%); GIP (1%); neutropenia (17%) | Median PFS; 17.3 vs 19.0 months; HR: 0.81 (0.70–0.94); p = 0.0041 | Median OS; 58.6 vs 58 months; HR: 0.99 (0.85–1.14); p = 0.85 | [34] |
| OCEANS | 484 | Platinum sensitive recurrent ovarian cancer§; ECOG PS 0–1 | iv. carboplatin (AUC 4) + iv. gemcitabine (1000 mg/m2) + placebo Q3w iv. carboplatin (AUC 4) + iv. gemcitabine (1000 mg/m2) + iv. bevacizumab (15 mg/kg) Q3w | HTN (17.4%); proteinuria (8.5%); bleeding (5.7%); F/A (1.6%); VTE (4%) | Median PFS; 8.4 vs 12.4 months; HR: 0.484 (0.388–0.605); p < 0.0001 | OS data immature; ORR; 78.5 vs 57.4%; p < 0.0001, DOR; 10.4 vs 7.4 months; HR: 0.534 (0.408–0.698) | [36] |
| AURELIA# | 361 | Platinum resistant recurrence¶; ≤2 prior chemotherapy regimens; no e/o rectosigmoid involvement; ECOG PS 0–2 | iv. paclitaxel (80 mg/m2) days 1, 8, 15, 22 Q4w or iv. topotecan (4 mg/m2) days 1, 8, 15 Q4w or iv. PLD (40 mg/m2) Q4w Chemotherapy as above plus iv. bevacizumab (15 mg/kg) Q3w | HTN (20.1%); proteinuria (12.8%); F/A (2.2%); GIP (1.7%); VTE (3.4%) | Median PFS; 3.4 vs 6.7 months; HR: 0.48; (0.36–0.60); p < 0.001 | Median OS; 13.3 vs 16.6 months; HR: 0.85 (0.66–1.08); p = 0.174 | [39] |
GOG 213 is a randomized Phase III trial designed to determine whether secondary cytoreductive surgery and/or the incorporation of bevacizumab to second-line chemotherapy improves progression-free survival in patients with platinum-sensitive recurrent ovarian cancer. At the time of manuscript production the data from GOG 213 were under embargo by the Society of Gynecologic Oncology.
†Investigational arms; a: Maintenance vs chemotherapy only arm; b: control vs bevacizumab throughout arms.
Investigational arms; a: Maintenance vs chemotherapy only arm; b: control vs bevacizumab throughout arms.
After protocol modifcation patients with optimally resected stage 3 disease were eligible.
Progression-free interval at least 6 months.
Based on the data from the AURELIA study, the US FDA approved bevacizumab for platinum-resistant, recurrent epithelial ovarian cancer on 14 November 2014 (see Table 1)
Progression-free interval less than or equal to 6 months.
AE: Adverse events; DOR: Duration of response; e/o: Evidence of; ECOG: Eastern Cooperative Oncology Group; F/A: Fistula/abscess; GIP: Gastrointestinal perforation; HR: Hazard ratio; HTN: Hypertension; iv.: Intravenous; ORR: Objective response rate; OS: Overall survival; PFS: Progression-free survival; PLD: Pegylated liposomal doxorubicin; PS: Performance status; VTE: Venous thromboembolism; Q3w: Every 3 weeks; Q4w: Every 4 weeks. Adapted with permission from [37].