Table II.
Pivotal clinical trials of first-line treatment with targeted agents in ovarian cancer patients.
| Trial | Number of patients | Treatment, first line | Patient population | Homologous recombination repair gene mutation status | PFS | HR | OS | HR | Adverse events |
|---|---|---|---|---|---|---|---|---|---|
| SOLO1 (Moore et al. 2018) (NCT01844986) |
391 | Maintenance monotherapy with olaparib or placebo | Newly diagnosed advanced (FIGO stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer (or a combination thereof) | BRCA mutation | At 41 months of follow-up, the median PFS for patients treated with olaparib was not reached, compared to 13.8 months for patients treated with placebo | HR for disease progression or death: 0.30 (95% CI: 0.23–0.41; p<0.001) | - | - | Adverse events were consistent with the known toxic effects of olaparib; the most frequent were nausea, fatigue and vomiting. Higher frequency of grade ≥3 anaemia and neutropenia in the olaparib versus placebo group |
| ICON7 (Perren et al. 2011) (NCT00483782) |
1528 | Carboplatin and paclitaxel given every 3 weeks for 6 cycles with or without bevacizumab given concurrently every 3 weeks for 5 to 6 cycles and continued for 12 additional cycles or until disease progression | Histologically confirmed, high-risk, early-stage disease (FIGO stage I or IIA) or advanced (FIGO stage IIB to IV) epithelial ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer | - | At 36 months, PFS was 20.3 months with standard therapy, as compared to 21.8 months with standard therapy plus bevacizumab | HR for disease progression or death with bevacizumab added: 0.81 (95% CI: 0.70–0.94; p=0.004) | - | - | Bevacizumab was associated with more toxic effects (most often hypertension of grade ≥2: 18% versus 2% with chemotherapy alone) |
| PAOLA-1 (Ray-Coquard et al. 2019) (NCT02477644) |
806 | Maintenance monotherapy with olaparib plus bevacizumab or bevacizumab alone | Newly diagnosed FIGO stage III–IV high-grade serous or endometrioid ovarian cancer, fallopian tube or primary peritoneal cancer. Patients had received first-line standard platinum-based chemotherapy plus bevacizumab and were in clinical complete or partial response | Overall population | PFS was 22.1 months with olaparib plus bevacizumab and 16.6 months in bevacizumab alone | HR for disease progression or death with olaparib added: 0.59 (95% CI: 0.49–0.72; p<0.001) | - | - | - |
| BRCA mutation | PFS was 37.2 months with olaparib plus bevacizumab and 21.7 months in bevacizumab alone | HR for disease progression or death with olaparib added: 0.31 (95% CI: 0.20–0.47) | |||||||
| PRIMA (Gonzalez-Martin et al. 2019) (NCT02655016) |
733 | Maintenance monotherapy with niraparib or placebo once daily in 28-day cycles for 36 months or until disease progression | Newly diagnosed FIGO stage III–IV, advanced cancer of the ovary, peritoneum, or fallopian tube who had received six to nine cycles of first-line platinum-based chemotherapy that resulted in a complete or partial response | Overall population | PFS was 13.8 months in the niraparib group versus 8.2 months in the placebo group | HR for disease progression or death: 0.62 (95% CI: 0.50–0.76; p<0.001) | At 24 months: 84% in the niraparib group versus 77% in the placebo group | HR: 0.70 (95% CI: 0.44–1.11) | Most common adverse events of grade 3 or higher were anaemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%) Higher frequency of myelosuppression and low-grade nausea in the niraparib group than in the placebo group |
| Homologous-recombination deficiency* | PFS was 21.9 months in the niraparib group versus 10.4 months in the placebo group | HR for disease progression or death: 0.43 (95% CI: 0.31–0.59; p<0.001) | At 24 months: 91% in the niraparib group versus 85% in the placebo group | HR: 0.61 (95% CI: 0.27–1.39) | |||||
| VELIA (Coleman et al. 2019a) (NCT02470585) |
1140 | Chemotherapy plus veliparib followed by veliparib maintenance (veliparib-throughout group); chemotherapy plus veliparib followed by placebo maintenance (veliparib-combination-only group); chemotherapy plus placebo followed by placebo maintenance (control group) | Previously untreated FIGO stage III or IV high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal carcinoma | Overall population | PFS was 23.5, 15.2 and 17.3 in the veliparib-throughout, the veliparib-combination-only, and the control groups, respectively | HR for disease progression or death: in veliparib-throughout versus control: 0.68 (95% CI: 0.56–0.83; P<0.001); in veliparib-combination-only versus control: 1.07 (95% CI: 0.90–1.29) in the intention-to-treat cohort | - | - | Veliparib was associated to a higher incidence of anaemia and thrombocytopenia when combined with chemotherapy, and to nausea and fatigue overall |
| Homologous-recombination deficiency* | PFS was 31.9, 18.1 and 20.5 months in the veliparib-throughout, the veliparib-combination-only, and the control groups, respectively | HR for disease progression or death: in veliparib-throughout versus control: 0.57 (95% CI: 0.43–0.76; p<0.001); in veliparib-combination-only versus control: 1.10 (95% CI: 0.86–1.41) | - | - | |||||
| BRCA mutation | PFS was 34.7, 21.1 and 22.0 months in the veliparib-throughout, the veliparib-combination-only, and the control groups, respectively | HR for disease progression or death: in veliparib-throughout versus control: 0.44 (95% CI: 0.28–0.68; p<0.001); in veliparib-combination-only versus control: 1.22 (95% CI: 0.82–1.80) | - | - |
BRCA: breast cancer gene; CI: confidence interval; FIGO: International Federation of Gynecology and Obstetrics; HR: hazard ratio; OS: overall survival; PFS: progression-free survival. *Defined as the presence of a BRCA deleterious mutation, a score of at least 42 on the my-Choice test, or both.