Table 3 Trials on combined treatment with immune checkpoint and PARP inhibitors.
| Trial | NCT02657889 (TOPACIO/KEYNOTE-162) | NCT02734004 (MEDIOLA) | NCT02734004 (MEDIOLA) | NCT02484404 |
|---|---|---|---|---|
| Abbreviations: CR = complete remission, DCR = disease control rate, HRD = homologous recombination deficit, ICB = immune checkpoint blockade, IHC = immunohistochemistry, IC = immune cells, CI = confidence interval, ORR = overall response rate, PD-1 = programmed cell death protein 1, PD-L1 = programmed cell death ligand 1, PFS = progression free survival, Pt = platinum, TC = tumour cells, WT = wild type | ||||
| Combined treatment | Niraparib + pembrolizumab | Olaparib + durvalumab | Olaparib + durvalumab + bevacizumab | Olaparib + durvalumab |
| Targeted ICB structure | PD-1 | PD-L1 | PD-L1 | PD-L1 |
| Dosing | Niraparib 200 mg qd Pembrolizumab 200 mg q21 |
Olaparib 300 mg bid after 4 weeks durvalumab 1500 mg q28 |
Olaparib 300 mg bid after 4 weeks durvalumab 1500 mg q28 + bevacizumab 10 mg/kg q14 |
Olaparib 300 mg bid Durvalumab 1500 mg q28 |
| Phase | Phase I/II (pooled) | Phase I/II | Phase II | Phase II |
| Study design | multicentre, open, single-arm | multicentre, open, single-arm | multicentre, open, single-arm | single-centre, open, single-arm |
| No. of patients | 62 (60 analysed) | 66 (64 analysed) | 31 | 35 |
| Population | Pt-resistant recurrence (response > 6 months to first-line Pt) 79% tBRCA-WT 18% tBRCA-mutated 35% HRD positive (Myriad) |
Pt-sensitive 50% gBRCA-WT 50% gBRCA-mutated |
Pt-sensitive 100% gBRCA-WT |
86% Pt-resistant (< 6 months) 77% BRCA-WT 23% BRCA-mutated 20% HRD positive (BROCA- HR) |
| Prior therapies | 1 – 5 (median 3) | gBRCA-mutated: 1 – 4 + lines (median 2) gBRCA-WT: 1 – 2 lines (median 1) |
1 – 2 lines (median 1) | 52% ≥ 4 lines (median 4) |
| Histology | not reported | 81% (26/32) serous 19% (6/32) non-serous not reported for gBRCA-WT |
not reported | 88% (31/35) high-grade serous 9% (3/35) endometrioid 3% (1/35) mucinous |
| PD-L1 status | 56% PD-L1 positive | |||
| ORR | 18% (11/60) | 53% (23/32) | 87% (27/31) | 14% (5/35) |
| CR | 5% (3/60) | 22% (7/32 gBRCA-mutated) | not reported | 0% (0/35) |
| ORR (BRCA mut ) | 18% (2/11) | 72% (23/32) | 37% (3/8) | |
| ORR (BRCA-WT) | 19% (9/47) | 34.4% (11/32) | 87% (27/31) | 7% (2/27) |
| ORR (PD-L1 positive) | 21% (7/33) | – | – | |
| ORR (PD-L1 negative) | 10% (2/21) | – | – | |
| ORR (HRD positive) | 14% (3/21) | – | – | |
| ORR (HRD negative) | 19% (6/32) | – | – | |
| DCR | 65% (39/60) | gBRCA-mutated: 66% gBRCA-WT: 28% |
77% (24/31) | 71% (25/35) |
| PFS | 3.4 months (95% CI 2.1 – 5.1 months) | 11.1 months (95% CI 8.2 – 15.9 months) 5.5 months (95% CI 3.6 – 7.5 months) |
14.7 months (95% CI 10.0 – 18.1 months) | 3.9 months (95% CI 2.0 – 7.25 months) |
| References | Konstantinopoulos et al. 8 | Drew et al. 155 , 156 | Drew et al. 156 | Lampert et al. 7 |