Table 1 Comparison of the major clinical trials testing an immune checkpoint inhibitor as monotherapy in ovarian cancer. These were solely single-arm trials.
| Immune checkpoint inhibitor | Nivolumab | Pembrolizumab | Pembrolizumab | Avelumab | Atezolizumab |
|---|---|---|---|---|---|
| Abbreviations: CPS = combined positive score, CR = complete remission, DCR = disease control rate, 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, PFI = platinum-free interval, PFS = progression-free survival, Pt = platinum, TC = tumour cells | |||||
| Targeted structure | PD-1 | PD-1 | PD-1 | PD-L1 | PD-L1 |
| Trial | UMIN00000571 | NCT02054806 (KEYNOTE-028) | NCT02674061 (KEYNOTE-100) | NCT01772004 (JAVELIN Solid Tumour) | NCT01375842 |
| Dosing | 1 mg/kg q14 (n = 10) or 3 mg/kg q14 (n = 10) |
10 mg/kg q14 | 200 mg q21 | 10 mg/kg q14 | Dose ranging trial 9/12 patients: 15 mg/kg |
| Phase | Phase II | Phase Ib | Phase II | Phase Ib | Phase Ib |
| Design | Single-centre, open | Multicentre, open | Multicentre, open | Multicentre, open | Multicentre, open |
| No. of patients | 20 | 26 | 376 (A: 285, B: 91) | 125 | 12 |
| Important inclusion criteria | Pt-resistant (≤ 6 months) | PD-L1 positive | Cohort A: 3 – 12 months PFI since last Pt Cohort B: ≥ 3 months PFI since last Pt |
75% Pt-resistant (≤ 3 months) | |
| Histology | 75% serous 15% endometrioid 10% clear cell |
46% “adenocarcinoma” 46% high-grade serous 4% endometrioid 4% transitional cell carcinoma |
75% high-grade serous 7% endometrioid 6% low-grade serous 5% clear cell 7% unspecified |
74.4% serous 3.2% mucinous 2.4% endometrioid 1.6% clear cell 18.4% unspecified |
80% serous 10% endometrioid 10% mixed endometrioid/clear cell |
| Prior therapies | ≥ 2 lines (median 4) | 73% ≥ 3 lines (median 4) | Cohort A: 1 – 3 lines Cohort B: 4 – 6 lines |
65% ≥ 3 lines (median 3) | ≥ 2 lines (> 90%) |
| PD-L1 testing | TC-IHC (four-level) on primary surgical specimen | CPS ≥ 1% | CPS | TC-IHC a. o. | IC-IHC (≥ 5% of tumour) |
| ORR | 15% (3/20) | 12% (3/26) |
8.5% (32/376)
(A: 8.1%, B: 9.9%) |
9.6% (12/125) | 22% (2/9) |
| CR | 10% (2/20) | 4% (1/26) | 1.9% (7/376) | 0.8% (1/125) | 11% (1/9) |
| ORR (PD-L1 positive) | 12.5% (2/16) | 12% (3/26) | 13.8% (CPS ≥ 10) 8.0% (CPS ≥ 1) 5.0% (CPS < 1) |
No correlation with PD-L1 status | 25% (2/8) |
| ORR (PD-L1 negative) | 25% (1/4) | – | 0% (0/1) | ||
| DCR | 45% | 19% (5/26) | 37.2% (140/376) | 52% (65/125) | 22% (2/9) |
| DOR | 3.5 months | not met in the 3 responders (> 20.5 months) | 10.2 months A: 8.3 months B: 23.6 months |
10.4 months | not reported for entire cohort |
| PFS | 3.5 months (95% CI 1.7 – 3.9 months) | 1.9 months (95% CI 1.8 – 3.5 months) | 2.1 months (A and B) | 2.6 months (95% CI 1.4 – 2.8 months) | 2.9 months (95% CI 1.3 – 5.5 months) |
| References | Hamanishi et al. 123 | Varga et al. 168 | Matulonis et al. 125 , 169 | Disis et al. 127 | Liu et al. 124 |