Table 3.
Studies without statistically significant benefit (n = 27)
| Treatment | Study name | n | Control | Design | Primary endpoint | PFS control | PFS gain | HR | OS control | OS gain | OS HR | ORR | Toxicity/QoL | ESMO grading | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Platinum-sensitive recurrence | |||||||||||||||
| Farletuzumab with carboplatin/taxane | 1100 | Placebo with carboplatin/taxane | Phase III RCT | PFS | 9.0 | 0.7 | 0.99 (0.81-1.21) | Not significant | 13 | ||||||
| Carboplatin/topotecan | 550 | Carboplatin plus physician choice either paclitaxel, gemcitabine or PLD | Phase III | PFS | 10 | 0 | Not provided | Not significant | 14 | ||||||
| Non-platinum-based CT | MITO-8 | 215 | Platinum-based CT | Phase III RCT | OS | 9 | −4 | Not provided | 24.5 | −2.7 | Not provided | PFS control arm significantly better | 5 | ||
| Carboplatin/paclitaxel micellar | 789 | Carboplatin/paclitaxel (conventional) | Phase III non-inferiority RCT | Non-inferiority for PFS | 10.1 | 0.2 | 0.86 (0.72-1.03) | Increased neutropenia, no difference in neurotoxicity | No score (no improvement in QoL or symptoms) | 15 | |||||
| Maintenance therapy after response to second-line platinum-based chemotherapy | |||||||||||||||
| Vismodegib maintenance after complete response to second- or third-line chemotherapy | 104 | Placebo | Phase II RCT | PFS | 5.8 | 1.7 | 0.79 (0.46-1.35) | Not significant | 29 | ||||||
| Carboplatin/paclitaxel plus bevacizumab | GOG-0213 | 674 | Carboplatin/paclitaxel plus placebo | Phase III RCT | OS | 37.3 | 4.9 | 0.83 (0.68-1.01) | Not significant | 26 | |||||
| Platinum-resistant recurrence | |||||||||||||||
| PLDa | 474 | Topotecan | RCT | PFS | 3.9 | −0.2 | NS | 13.8 | 0.69 | 0.82 (0.68-1.00) | Not significant | 46,47 | |||
| Epidoxorubicin plus paclitaxela | 234 | Paclitaxel | Phase III RCT | OS | 14.0 | −2.0 | NS | Not significant | 48 | ||||||
| PLD | 195 | Gemcitabine | Phase III RCT | PFS | 3.1 | 0.5 | NS | Not significant | 49 | ||||||
| PLDa | 153 | Gemcitabine | Phase III RCT | TTP | 3.7 | 0.9 | NS | Not significant | 50 | ||||||
| Topotecan/etoposide (TE) or topotecan/gemcitabine | 502 | Topotecan | Phase III RCT | OS | 17.2 | 0.6 (TE) | 1.18 (0.90-1.53) | Not significant | 51 | ||||||
| Canfosfamidea | 461 | PLD or topotecan | Phase III RCT | OS | 13.5 | −5.0 | 1.71 | Control arm significantly better | 52 | ||||||
| Pertuzumab plus gemcitabine | 130 | Gemcitabine plus placebo | Phase II RCT | PFS | 2.9 | 0 | 0.66 (0.43-1.03) | Not significant | 53 | ||||||
| Pertuzumab plus carboplatin and either paclitaxel or gemcitabine | 149 | Carboplatin and either paclitaxel or gemcitabine | Phase II RCT | PFS | 8.6 | −0.7 | 1.16 (0.90-1.49) | Not significant | 54 | ||||||
| Paclitaxel/carboplatin OR paclitaxel/topotecan | 165 | Paclitaxel | Phase II RCT | PFS | 3.7 | 1.1 1.7 |
0.92, NS 0.95, NS |
Not significant | 55 | ||||||
| Olaparib 200 mg or 400 mga | 97 | PLD | Phase II RCT | PFS | 7.1 | NA | 0.88 (0.62-1.28) | Not significant | 56 | ||||||
| Patupilone | 829 | PLD | Phase III RCT | OS | 12.7 | 0.5 | 0.93 (0.79-1.09) | Not significant | 57 | ||||||
| Docetaxel plus vandetanib | 129 | Docetaxel | RCT | PFS | 3.5 | −0.5 | 1.01 (0.79-1.27) | Not significant | 58 | ||||||
| Seribantumab plus paclitaxel | 223 | Paclitaxel | RCT | PFS | 3.7 | 0.1 | 1.03 (0.74-1.43) | Not significant | 59 | ||||||
| Motolimod plus PLD | 297 | PLD | Phase II RCT | PFS | 5.2 | −0.4 | 1.21 | 18.9 | −0.8 | 1.22 | Not significant | 60 | |||
| Oncolytic reovirus plus paclitaxel | 108 | Paclitaxel | Phase II RCT | PFS | 4.3 | 0.1 | 1.11 (0.78-1.59) | Not significant | 61 | ||||||
| Pazopanib plus paclitaxel | 106 | Paclitaxel | Phase II RCT | PFS | 6.2 | 1.3 | 0.84 (0.57-1.22) | 23.3 | −2.6 | 1.04 (0.60-1.79) | Not significant | 62 | |||
| Cabozantinib plus paclitaxel | 174 | Paclitaxel | RCT | PFS | 5.5 | −0.2 | 1.11 (0.77-1.61) | Not reached | 2.27 (1.17-2.63) | Control arm significantly better OS | 63 | ||||
| Olaratumab plus PLD | 123 | PLD | Phase II RCT | PFS | 4.0 | 0.2 | 1.04 (0.70-1.56) | 16.2 | 0.4 | 1.1 (0.70-1.71) | Not significant | 64 | |||
| Linsitinib (two different regimens) plus paclitaxel | 152 | Paclitaxel | Phase I/II RCT | PFS | 5.6 | −1.4 | 1.2 (0.75-1.91) | Not significant | 65 | ||||||
| Alisertib plus paclitaxel | 191 | Paclitaxel | Phase I/II RCT | PFS | 4.7 | 2.0 | 0.75 (0.58-0.96) | Not significant | 66 | ||||||
| Carboplatin plus guadecitabine | 100 | Physician choice PLD, topotecan, paclitaxel or gemcitabine | Phase II RCT | PFS | 2.1 | 1.6 | 0.69 (0.46-1.0) | Not significant | 67 | ||||||
HR, hazard ratio; ITT, intention to treat; MCBS, Magnitude of Clinical Benefit Scale; NS, not significant; OS, overall survival; PFS, progression-free survival; PLD, pegylated liposomal doxorubicin; QoL, quality of life; RCT, randomised controlled trials; TTP, time to progression.
a
Trial did also include platinum-sensitive patients.