Table 1.
Key results from reported prospective trials investigating HRD status as a biomarker for PARPi response
| Trial name/study number | PARPi used | Treatment setting | Study population | HRD testing method | Results |
|---|---|---|---|---|---|
| SOLO1 (NCT01844986) | Olaparib | Maintenance therapy after CR/PR to frontline platinum-based chemotherapy | Advanced newly diagnosed OC patients with a deleterious or suspected deleterious BRCA1/2 mutation | Germline or somatic BRCA1/2 sequencing | Median PFS for olaparib versus placebo: 56.0 versus 13.8 months (HR 0.33, 95% CI 0.25-0.43) |
| PRIMA (NCT02655016) | Niraparib | Advanced newly-diagnosed OC patients at high risk for recurrence | Myriad myChoice CDx (HRD+ GIS ≥42) |
Intention-to-treat: Median PFS for niraparib versus placebo: 13.8 versus 8.2 months (HR 0.62, 95% CI 0.50-0.76) BRCAm: Median PFS for niraparib versus placebo: 22.9 versus 10.9 months (HR 0.40, 95% CI 0.27-0.62) HRD+/BRCAwt: Median PFS for niraparib versus placebo: 19.6 versus 8.2 months (HR 0.50, 95% CI 0.31-0.83) HRp: Median PFS for niraparib versus placebo: 8.1 versus 5.4 months (HR 068, 95% CI 0.49-0.94) HRnd: Median PFS for niraparib versus placebo: not reported (HR 085, 95% CI 0.51-1.43) |
|
| PAOLA1 (NCT02477644) | Olaparib + bevacizumab | Advanced newly diagnosed patients with OC | Myriad myChoice CDx (HRD+ GIS ≥42) |
Intention-to-treat: Median PFS for olaparib versus placebo: 22.1 versus 16.6 months (HR 0.59, 95% CI 0.49-0.72) BRCAm: Median PFS for olaparib versus placebo: 37.2 versus 21.7 months (HR 0.31, 95% CI 0.28-0.66) HRD+/BRCAwt: Median PFS for olaparib versus placebo: 28.1 versus 16.6 months (HR 0.43, 95% CI 0.28-0.66) HRp + HRnd: Median PFS for olaparib versus placebo: 16.9 versus 16.0 months (HR 0.92, 95% CI 0.72-1.17) |
|
| VELIA (NCT02470585) | Veliparib | Advanced newly diagnosed patients with OC | Myriad myChoice CDx (HRD+ GIS ≥33) |
Intention-to-treat: Median PFS for veliparib versus placebo: 23.5 versus 17.3 months (HR 0.68, 95% CI 0.56-0.83) BRCAm Median PFS for veliparib versus placebo: 34.7 versus 22 months (HR 0.44, 95% CI 0.28-0.68) HRD+/BRCAwt: Median PFS for veliparib versus placebo: 22.9 versus 19.8 months (HR 0.74, 95% CI 0.52-1.06) HRp: Median PFS for veliparib versus placebo: 15.0 versus 11.5 months (HR 0.81, 95% CI 0.60-1.09) |
|
| ARIEL2 Part 1 (NCT01891344) | Rucaparib | Maintenance therapy after CR/PR to platinum-based chemotherapy for relapsed disease | Recurrent platinum-sensitive OC | Foundation Medicine T5 NGS assay (genomic LOH high ≥14%) |
BRCAm: Median PFS 12.8 months (95% CI 9.0-14.7) LOH high: Median PFS: 5.7 months (95% CI 5.3-7.6) LOH low: Median PFS: 5.2 months (95% CI 3.6-5.5) |
| ARIEL3 (NCT01968213) | Recurrent platinum-sensitive OC | Foundation Medicine T5 NGS assay (genomic LOH high ≥16%) |
Intention-to-treat: Median PFS for rucaparib versus placebo: 10.8 versus 5.4 months (HR 0.36, 95% CI 0.30-0.45) BRCAm: Median PFS for rucaparib versus placebo: 16.6 versus 5.4 months (HR 0.23, 95% CI 0.16-0.34) LOH high: Median PFS for rucaparib versus placebo: 13.6 versus 5.4 months (HR 0.32, 95% CI 0.24-0.42) |
||
| NOVA (NCT01847274) | Niraparib | Recurrent platinum-sensitive OC | Myriad myChoice CDx (HRD+ GIS ≥42) |
BRCAm: Median PFS for niraparib versus placebo: 21.0 versus 5.5 months (HR 0.27, 95% CI 0.17-0.41) HRD+/BRCAwt: Median PFS for niraparib versus placebo: 12.9 versus 3.8 months (HR 0.38, 95% CI 0.24-0.59) BRCAwt: Median PFS for niraparib versus placebo: 9.3 versus 3.9 months (HR 0.45, 95% CI 0.34-0.61) |
|
| Study19 (NCT00753545) | Olaparib | Recurrent platinum-sensitive OC | N/A |
Intention-to-treat: Median PFS for olaparib versus placebo: 8.4 versus 4.8 months (HR 0.35, 95% CI 0.25-0.49) |
|
| SOLO2 (NCT01874353) | Olaparib | Recurrent platinum-sensitive OC | Germline or somatic BRCA1/2 sequencing |
Intention-to-treat: Median PFS for olaparib versus placebo: 19.1 versus 5.5 months (HR 0.30, 95% CI 0.22-0.41) |
|
| QUADRA (NCT02354586) | Niraparib | Treatment of relapsed disease after three or more prior chemotherapy regimens | Relapsed OC that has received three or more prior chemotherapy regimens, irrespective of platinum-sensitivity status | Myriad myChoice CDx (≥42) and germline BRCA status testing |
Platinum-sensitive, BRCAm: ORR 39% Platinum-sensitive, HRD+: ORR 26% Platinum-sensitive, HRDp or HRDnd: ORR 4% Platinum-resistant/refractory, BRCAm: ORR 27% Platinum-resistant/refractory, HRD+: ORR 10% Platinum-resistant/refractory, HRDp or HRDnd: ORR 3% |
| Study42 (NCT01078662) | Olaparib | Relapsed germline BRCA1/2-mutated OC that has received three or more prior chemotherapy regimens | Germline BRCA testing | ORR 34% Median duration of response: 7.9 months (95% CI 5.6-9.6) |
|
| Study10 (NCT01482715) | Rucaparib | Treatment of relapsed disease after two to four prior chemotherapy regimens | Relapsed germline BRCA1/2-mutated OC that has received two to four prior chemotherapy regimens | Germline BRCA testing | ORR 59.5% |
BRCAm, BRCA-mutant; BRCAwt, BRCA wild type; CI, confidence interval; CR, complete response; HR, hazard ratio; HRnd, HR not detected; HRp, HR proficient; NGS, next-generation sequencing; OC, ovarian cancer; ORR, objective response rate; PFS, progression-free survival; PR, partial response.