Table 1.
Phase III studies scored for clinical benefit (n = 14)
| Treatment | Study name | Subgroups | n | Control | Primary endpoint | PFS control | PFS gain | HR | OS control | OS gain | OS HR | ORR | Toxicity/QoL adjustment | MCBS score (form) | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Platinum-sensitive recurrence | |||||||||||||||
| Carboplatin/PLD | CALYPSO | 976 | Carboplatin plus paclitaxel | PFS (non-inferiority) | 9.4 | 1.9 | 0.82 (0.72-0.94) | 30.7 | 2.3 | 0.99 (0.85-1.16) | Global QoL equal but better scores on subscales for carboplatin/PLD (less neurotoxicity, better body image; early discontinuation in 6% versus 15%) | 3 (2c) | 8,9 | ||
| Paclitaxel plus platinum-based chemotherapy | ICON4/AGO-OVAR 2.2 | 802 | Platinum monotherapy (carboplatin or cisplatin) | OS | 24 | 5 | 0.82 (0.69-0.97) | 4 (2a) | 7 | ||||||
| Carboplatin plus gemcitabine | 356 | Carboplatin | PFS | 5.8 | 2.8 | 0.72 (0.58-0.90) | 17.3 | 0.7 | 0.96 (0.75-1.23) | −1 No QoL benefit and no OS benefit |
2 (2b) | 10 | |||
| Carboplatin/PLD/bevacizumabb | 682 | Carboplatin/gemcitabine/bevacizumab | PFS | 11.7 | 1.7 | 0.81 (0.68-0.91) | 27.8 | 4.1 | 0.81 (0.67-0.98) | 1 (2b) | 11 | ||||
| Carboplatin doublet plus bevacizumab | MITO16b/MANGO-OV2/ENGOT-ov17 | 406 | Carboplatin doublet | PFS | 8.8 | 3 | 0.51 (0.41-0.65) | 3 (2b) | 12 | ||||||
| Maintenance therapy after response to second-line platinum-based chemotherapy | |||||||||||||||
| Cediranib | ICON6 |
|
282 | Placebo | PFS | 8.7 | 2.3 | 0.56 (0.44-0.72) | 0.86 (0.67-1.11) | −1 No QoL benefit and no OS benefit |
1 (2b) | 21,28 | |||
| Niraparib |
|
553 203 350 162 |
Placebo | PFS | — 5.5 3.9 3.8 |
— 14.5 5.4 9.1 |
— 0.27 (0.17-0.41) 0.45 (0.34-0.61) 0.38 (0.24-0.59) |
3 (2b) 3 (2b) |
17 | ||||||
| Rucaparib (ITT) | ARIEL3 |
|
564 196 354 |
Placebo | PFS | 5.4 5.4 5.4 |
5.4 11.2 8.2 |
0.36 (0.30-0.45) 0.23 (0.16-0.34) 0.32 (0.24-0.42) |
3 (2b) 3 (2b) 3 (2b) |
18 | |||||
| Olaparib (tablets) | SOLO2 |
|
295 | Placebo | PFS | 5.5 | 13.6 | 0.30 (0.22-0.41) | 38.8 | 12.9 | 0.74 (0.54-1.00) | −1 for no OS benefit | 2 (2b) | 20,27 | |
| Addition of bevacizumab to carboplatin plus gemcitabine | OCEANS | 484 | Carboplatin plus gemcitabine | PFS | 8.4 | 4 | 0.48 (0.39-0.61) | 32.9 | 0.7 | 0.95 (0.77-1.18) | −1 No QoL benefit and no OS benefit |
2 (2b) | 22,23 | ||
| Platinum-resistant recurrence | |||||||||||||||
| Trabectedin plus PLDa | 672 | PLD | PFS | 5.8 | 1.5 | 0.79 (0.65-0.96) | 18.9 | 3.3 | 0.86 (0.72-1.02) | −1 No QoL benefit and no OS benefit |
2 (2b) | 34,35 | |||
| Addition of bevacizumab to standard chemotherapy (either PLD, paclitaxel or topotecan) | AURELIA | 361 | Standard chemotherapy (either PLD, paclitaxel or topotecan) | PFS | 3.4 | 3.3 | 0.48 (0.38-0.60) | 13.3 | 3.3 | 0.85 (0.66-1.08) | +1 QoL benefit | 4 (2b) | 30,31 | ||
| Trebananib plus paclitaxela | TRINOVA-1 | 919 | Paclitaxel | PFS | 5.4 | 1.8 | 0.66 (0.57-0.77) | 18.3 | 1 | 0.95 (0.85-1.11) | −1 No QoL benefit and no OS benefit |
2 (2b) | 36 | ||
| Topotecana | 235 | Paclitaxel | ORR | ORR 21% | 2 (3) | 45 | |||||||||
gBRCA, germline BRCA; HR, hazard ratio; HRD, homologous recombination deficiency; ITT, intention to treat; MCBS, Magnitude of Clinical Benefit Scale; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; QoL, quality of life.
a
Trial did also include platinum-sensitive patients.
b
Trial not scored for OS (form 2a) as OS was exploratory and not corrected for multiple testing.