Table 1.
Key clinical trials showing clinical efficacy of PARP inhibitors in ovarian cancer
| Clinical trial/phase | Setting | Treatments | Patients (randomised) | Results median PFS in months (with 95% CI) | Hazard ratio (95%CI), p value | References | |||
|---|---|---|---|---|---|---|---|---|---|
|
SOLO-1 III |
Newly diagnosed histologically confirmed advanced high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer, FIGO stage III or IV, deleterious or suspected deleterious germline or somatic BRCA1/2 mutation, after 6–9 cycles of platinum-based chemotherapy with CR or PR, Surgery (primary or interval) allowed, no bevacizumab | Olaparib versus Placebo | n = 391 |
Olaparib arm All (n=260) NR (at time of publication) |
Placebo arm All (n = 131) 13.8 |
HR 0.30 (0.26–0.41), p < 0.001 | [13] | ||
| PAOLA-1 III |
Newly diagnosed high-grade serous or endometrioid ovarian cancer fallopian tube or primary peritoneal cancer, FIGO stage III or IV, minimum of six and max. of nine cycles of platinum-taxane based chemotherapy with NED/CR/PR, maintenance with bevacizumab and a minimum of three cycles of bevacizumab with last three cycles of chemotherapy Surgery (primary or interval) allowed, HRD testing with myChoice® HRD Plus, Myriad Genetics |
Olaparib plus Bevacizumab versus Placebo plus Bevacizumab | n = 806 |
Olaparib arm All (n = 537) 22.1 BRCAm (n = 157): 37.2 HRDpos, incl. BRCAm (n = 255) 37.2 HRD-pos, BRCAwt (n = 97): 28.1 BRCAwt+HRD-neg/unknown) (n = 282) 16.9 |
Placebo arm All (n = 269) 16.6 BRCAm (n = 80): 21.7 HRDpos. incl. BRCAm (n = 132) 17.7 HRD-pos. BRCAwt (n = 55): 16.6 BRCAwt+HRD-neg/unknown) (n = 137) 16.0 |
HR 0.59 (0.49–0.72), p < 0.0001 HR 0.31 (0.20–0.47) HR 0.33 (0.25–0.45) HR 0.43 (0.28–0.66) HR 0.92 (0.72–1.17) |
[11] | ||
|
PRIMA III |
Newly diagnosed primary histologically confirmed advanced cancer of the ovary, peritoneum, or fallopian tube, FIGO stage III required visible residual tumour after primary surgery (unless interval surgery) or FIGO IV, a minimum of four cycles of platinum-based chemotherapy with CR/PR, Surgery (primary or interval) allowed, HRD testing with myChoice®, Myriad Genetics | Niraparib versus Placebo |
All (n = 799) HRDpos (n = 373) |
Niraparib arm All (n = 487): 13.8 (11.5–14.9) HRDpos (n = 247): 21.9 (19.3-NE) HRDpos+ BRCAm (n = 152) 22.1 (19.3–NE) HRDpos +BRCAwt (n = 95) 19.6 (13.6–NE) HR-proficient (n = 169): 8.1 (5.7–9.4) |
Placebo arm All (n = 246): 8.2 (7.3–8.5) HRDpos (n = 126): 10.4 (8.1–12.1) HRDpos+ BRCAm(n = 152) 10.9 (8.0–19.4) HRDpos +BRCAwt (n = 55) 8.2 (6.7–16.8) HR-proficient (n = 80): 5.4 (4.0–7.3) |
HR 0.62 (0.5–0.75), p < 0.0001 HR 0.43 (0.31–0.59), p < 0.0001 HR 0.40 (0.27–0.62), p < 0.001 HR 0.50(0.31–0.83), p = 0.006 HR 0.68(0.49–0.94), p = 0.020 |
[12] | ||
|
VELIA III |
Newly diagnosed primary, histologically confirmed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, FIGO stage III or IV, a minimum of six cycles of carboplatin/Paclitaxel chemotherapy, Surgery (primary or interval) allowed, HRD testing with myChoice® CDx or BRACAnalysis CDx, Myriad Genetics |
Veliparib throughout (during chemotherapy and maintenance) (V-throughout) versus Veliparib during chemotherapy with placebo maintenance (VCTXonly) versus Placebo throughout chemotherapy and as maintenance) |
All (n = 1140) V-throughout (n = 375) VCTX-only (n = 383) Placebo (n = 382) |
Veliparib throughout arm ITT (n = 382) 23.5 (19.3–26.3) HRDpos (n = 214) 31.9 (25.8–38.0) BRCAm n = 108) 34.7 (31.8–xx) |
Veliparib during CTx only arm ITT (n = 383) 15.2 (14.1–17.3) HRD (n = 206) 18.1 (16.4–22.7) BRCAm n = 98) 21.1 (17.0–25.5) |
Placebo arm ITT (17.3 ( 15.1–19.1) HRDpos (n = 207) 20.5 (17.8–22.8) BRCAm (n = 92) 22,0 (17.8–29.1) ITT (n = 375) 17.3 (15.1–19.1) HRD (n = 207) 20.5 (17.8–22.8) BRCAm (n = 92) 22.0 (17.8–29.1) |
HR 0.68 (0.56–0.83), p < 0.001 HR 0.57 (0.43–0.76), p < 0.001 HR 0.44 (0.28–0.68), p < 0.001 HR 1.07 (0.90–1.29) HR 1.10 (0.86–1.41) HR 1.22 (0.82–1.80) |
[10] | |
|
Study 19 II |
Recurrent platinum-sensitive high-grade serous ovarian or fallopian-tube cancer or primary peritoneal cancer, at least two courses of platinum-based chemotherapy, (a minimum of four cycles) in last platinum-based chemotherapy with CR/PR |
Olaparib (capsules) versus Placebo | n = 265 |
Olaparib arm All (n = 136) 8.4 (7.4–11.5) BRCAwt (n = 57) 7.4(5.5–10.3) BRCAm (n = 74) 11.2 (8.3–NC) |
Placebo arm All(n = 129) 4.8 (4.0–5.5) BRCAwt (n = 61) 5.5 (3.7 -5.6) BRCAm(n = 62) 4.3 (3.0–5.4) |
HR 0.35 (0.25–0.49), p < 0.0001 HR 0.54 (0.34–0.85), p < 0.0075 HR 0.18 (0.10–0.31), p < 0.0001 |
[15, 31] | ||
|
NOVA II |
Recurrent platinum-sensitive ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with predominantly high-grade serous histologic features, at least two courses of platinum-based chemotherapy, (a minimum of four cycles) in last platinum-based chemotherapy with CR/PR, HRD testing with myChoice®, Myriad Genetics | Niraparib versus Placebo |
All (n = 553) Niraparib (n = 372) Placebo (n = 181) |
Niraparib arm gBRCAm cohort (n = 138) 21.0 Non-gBRCA with HRD (n = 106) 12.9 Non-gBRCA cohort (n = 234) 9.3 |
Placebo arm gBRCAm cohort (n = 65) 5.5 Non-gBRCA with HRD (n = 56) 3.8 Non-gBRCA coh-ort (n = 116) 3.9 |
HR 0.27 ( 0.17–0.41), p < 0.001 HR 0.38 ( 0.24–0.59), p < 0.001 HR 0.45 (0.34–0.61) |
[14] | ||
|
SOLO-2 III |
Recurrent, HGSOC or high-grade endometrioid cancer, including primary peritoneal or fallopian tube cancer in patients with a predicted or suspected deleterious somatic or germline BRCA1/2 mutation, at least two courses of platinum-based chemotherapy, a mini of four cycles) in last platinum-based chemotherapy with CR/PR | Olaparib versus placebo | n = 295 |
Olaparib All (n = 196) 19.1 (16.3–25.7) |
Placebo All (n = 99) 5.5 (5.2–5.8) |
HR 0.30 (0.22–0.41), p < 0.0001 | [16] | ||
|
Ariel-2 (part 1) II |
Recurrent high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal carcinoma, at least one prior platinum-based chemotherapy, more than 6 months PFS after last platinum-based chemotherapy HRD (LOH) measured by NGS | Rucaparib | n = 194 |
BRCAm (n = 40) 12.8 (9.0–14.7) BRCAwt and high LOH (n = 82) 5.7 (5.3–7.6) BRCAwt and low LOH (n = 70) 5.2 (3.6–5.5) |
HR 0.27 (0.16–0.44), p < 0.0001 (compared to BRCAwt and low LOH) BRCAwt and high LOH HR 0.62 (0.42 0.90), p = 0.011 (compared to BRCAwt and low LOH) |
[17] | |||
|
Ariel-3 II |
Recurrent platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer, at least two prior platinum-based chemotherapy, more than 6 months PFS after last platinum-based chemotherapy (CR/PR) before trial therapy, HRD (LOH) measured by NGS | Rucaparib versus Placebo | n = 564 |
Rucaparib arm ITT (n = 375) 10.8 (8.3–11.4) BRCAm (n = 130) 16.6 (13.4–22.9) HRD (n = 236) 13.6 (10.9–16.2) |
Placebo arm ITT(n = 189) 5.4 (5.3–5.5) BRCAm (n = 66) 5.4 (3.4–6.7) HRD (n = 118) 5.4 (5.1–5.6) |
HR 0.36 (0.30–0.45) HR 0.23 (0.16–0.34), p < 0.0001 HR 0.32 (0.24–0.42), p < 0.0001 |
[18] | ||