Table 2 Phase III trials on the combined treatment with immune checkpoint blockade and chemotherapy in advanced ovarian cancer.
| Trial | NCT02718417 (JAVELIN Ovarian 100) | NCT03038100 (IMagyn050) | NCT02580058 (JAVELIN Ovarian 200) |
|---|---|---|---|
| * did not meet predefined level of significance Abbreviations: ECOG PS = Eastern Co-operative Oncology Group Performance Status, ICB = immune checkpoint blockade, ICH = immunohistochemistry, HR = hazard ratio, OS = overall survival, PD-L1 = programmed cell death ligand 1, PLD = pegylated liposomal doxorubicin, PFS = progression-free survival | |||
| Immune checkpoint inhibitor used | Avelumab | Atezolizumab | Avelumab |
| Targeted ICB structure | PD-L1 | PD-L1 | PD-L1 |
| Arms | A) 6 × carboplatin/paclitaxel → avelumab for 24 months B) 6 × carboplatin/paclitaxel/avelumab → avelumab for 24 months C) 6 × carboplatin/paclitaxel |
A) 6 × carboplatin/paclitaxel/bevacizumab + placebo → maintenance with bevacizumab and placebo B) 6 × carboplatin/paclitaxel/bevacizumab + atezolizumab → maintenance with bevacizumab and atezolizumab |
A) Avelumab B) Avelumab + PLD C) PLD |
| Study design | Multicentre, randomised (1 : 1 : 1), open | Multicentre, randomised (1 : 1), double-blind | Multicentre, randomised (1 : 1 : 1), open |
| Primary endpoint(s) | PFS | PFS | PFS, OS |
| No. of patients (n) | 998 | 1301 | 566 |
| Population | First-line therapy FIGO III – IV, ECOG PS 0 – 1, after debulking or as neoadjuvant therapy (31.6% surgery without macroscopic residual tumour) |
First-line therapy FIGO III – IV, ECOG PS 0 – 2, after debulking (75%) or as neoadjuvant therapy/interval debulking (25%) (7.4% surgery without macroscopic residual tumour) |
Platinum-resistant/refractory recurrence ≤ 3 prior therapies no prior therapy in Pt-resistant recurrence |
| Histology | 76% high-grade serous 6.2% low-grade serous 5.5% clear cell 3.2% endometrioid 8.7% other |
76% high-grade serous 10% low-grade serous 12% high-grade non-serous 4% clear cell |
69% high-grade serous 4% low-grade serous 13% clear cell 3% endometrioid 10% other |
| Definition “PD-L1 positive” | ≥ 1% tumour cells positive and/or ≥ 5% immune cells positive (Ventana SP263 IHC assay) |
≥ 1% immune cells positive (Ventana SP142 IHC assay) |
≥ 1% tumour cells positive and/or ≥ 5% immune cells positive (Ventana SP263 IHC assay) |
| PD-L1 status | 48.8% PD-L1 positive 32.6% PD PD-L1 negative |
40% PD-L1 positive 60% PD PD-L1 negative |
57% PD-L1 positive |
| Median PFS | A) 16.8 months (HR 1.43 vs. C, p = 0.989) B) 18.1 months (HR 1.14 vs. C, p = 0.794) C) Median not reached |
A) 18.4 months B) 19.5 months (HR 0.92, p = 0.28) |
A) 1.9 months (HR 1.68 vs. C,> 0.999) B) 3.7 months (HR 0.78 vs. C, p = 0.030*) C) 3.5 months |
| Overall survival (OS) | No difference in OS to date | No difference in OS to date | A) 11.8 months (HR 1.14 vs. C, p = 0.8) B) 15.7 months (HR 0.89 vs. C, p = 0.21) C) 13.1 months |
| Median PFS (PD-L1 positive) | A) Median not met (HR 1.23 vs. C, p = 0.357) B) Median not met (HR 0.98 vs. C, p = 0.918) C) Median not met |
A) 18.5 months B) 20.8 months (HR 0.80, p = 0.038*) |
A) 1.9 months (HR 1.45 vs. C, p = 0.030) B) 3.7 months (HR 0.65 vs. C, p = 0.0149) C) 3.0 months |
| Median PFS (PD-L1 negative) | A) 16.8 months (HR 1.02 vs. C, p = 0.950) B) 13.9 months (HR 1.36 vs. C, p = 0.232) C) Median not met |
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| References | Ledermann et al. 133 | Moore et al. 5 | Pujade-Lauraine et al. 135 |