Table III.
Pivotal clinical trials of second-line treatment with targeted agents in ovarian cancer patients.
| Trial | Number of patients | Treatment, second or further line | Patient population | Homologous recombination repair gene mutation status | PFS | HR | OS | HR | Adverse events |
|---|---|---|---|---|---|---|---|---|---|
| Study 19 (Ledermann et al. 2014) (NCT00753545) |
265 | Maintenance monotherapy with olaparib versus placebo | Platinum-sensitive recurrent serous ovarian cancer | BRCA mutation | 11.2 months (95% CI, 8.3–not calculable) versus placebo 4.3 months (3.0–5.4) | 0.18 (0.10–0.31); p<0.0001 | 34.9 months (95% CI, 29.2–not calculable versus placebo 31.9 months (23.1–40.7) | 0.73 (95% CI 0.45–1.17); p=0.19 | Grade 3 or worse: fatigue (in ten [7%] patients in the olaparib group versus four [3%] in the placebo group) and anaemia (seven [5%] versus one [<1%]) |
| No BRCA mutation | 7.4 months (5.5–10.3) versus placebo 5.5 months (3.7–5.6) | 0.54 (0.34–0.85); p=0.0075 | 24.5 months (19.8–35.0) versus placebo 26.2 months (22.6–33.7) | 0.99 (95% CI 0.63–1.55); p=0.96 | |||||
| SOLO2/ENGOT-Ov21 (Pujade-Lauraine et al. 2017) (NCT01874353) |
295 | Maintenance monotherapy with olaparib versus placebo | Platinum-sensitive, recurrent high-grade serous ovarian cancer or endometrioid cancer | BRCA mutation | 19.1 months (95% CI, 16.3–25.7) versus placebo 5.5 months (5.2–5.8) | 0.30 (95% CI 0.22–0.41) | Grade 3 or worse: (38 [19%] of 195 patients in the olaparib group versus two [2%] of 99 patients in the placebo group), fatigue or asthenia (eight [4%] versus two [2%]), and neutropenia (ten [5%] versus four [4%]) | ||
| NOVA (Mirza et al. 2016) (NCT01847274) |
553 | niraparib (300 mg) or placebo once daily until disease progression | Platinum-sensitive recurrent, ovarian, fallopian tube, or peritoneal cancer | Germline BRCA mutation | 21.0 months compared with 5.5 months in the placebo group | 0.27 (95% CI, 0.17 to 0.41); P<0.001 | Most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anaemia (in 25.3%), and neutropenia (in 19.6%) | ||
| No germline BRCA mutation but with homologous recombination deficiency | 12.9 months versus 3.8 months in the placebo group | 0.38 (95% CI, 0.24 to 0.59); P<0.001 | |||||||
| No germline BRCA mutation | 9.3 months versus 3.9 months in the placebo group | 0.45 (95% CI, 0.34 to 0.61); P<0.001 | |||||||
| NOVA subgroup analysis in patients aged ≥70 years (Fabbro et al. 2019) (NCT01847274) |
95 (≥70 years) | Niraparib (300 mg) or placebo once daily until disease progression | Platinum-sensitive recurrent, ovarian, fallopian tube, or peritoneal cancer | Germline BRCA mutation | Not reached versus placebo 3.7 months | 0.09 (95% CI, 0.01 to 0.73) | Grade 3 or worse: thrombocytopenia event (34.4%), anaemia event (13.1%), and neutropenia event (16.4%) | ||
| No germline BRCA mutation | 11.3 months compared with placebo 3.8 months | 0.35 (95% CI, 0.18 to 0.71) | |||||||
| ARIEL2 (Swisher et al. 2017) (NCT01891344) |
206 | Oral rucaparib 600 mg twice daily or placebo | Platinum-sensitive, recurrent, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer | BRCA mutation | 12.8 months (95% CI, 9.0–14.7) | 0.27 (95% CI 0.16–0.44, p<0.0001) | Most common grade 3 or worse treatment-emergent adverse events were anaemia or decreased haemoglobin (45 [22%] patients), and elevations in alanine aminotransferase or aspartate aminotransferase (25 [12%]). | ||
| BRCA mutant or BRCA wild-type and high LOH | 5.7 months (95% CI, 5.3–7.6) | 0.62 (0.42–0.90, p=0.011) compared to low LOH group | |||||||
| BRCA wildtype and low/intermediated LOH | 5.2 months (95% CI, 3.6–5.5) | ||||||||
| ARIEL3(Coleman et al. 2017) (NCT01968213) |
564 | Oral rucaparib 600 mg twice daily or placebo in 28-day-cycles | Platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma | BRCA mutation | 16.6 months (95% CI, 13.4–22.9) versus 5.4 months (3.4–6.7) | 0.23 (95% CI, 0.16–0.34); p<0.0001 | Grade 3 or worse: anaemia or decreased haemoglobin concentration (70 [19%] patients versus one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] versus none) | ||
| BRCA mutant or BRCA wild-type and high LOH | 13.6 months (10.9–16.2) versus 5.4 months (5.1–5.6) | 0.32 (0.24–0.42); p<0.0001 | |||||||
| BRCA wildtype and low/intermediated LOH | 0.8 months (8.3–11.4) versus 5.4 months (5.3–5.5) | 0.36 (0.30–0.45); p<0.0001 |
BRCA: breast cancer gene; CI: confidence interval; HR: hazard ratio; LOH: loss of heterozygosity; OS: overall survival; PFS: progression-free survival.