Table 2.
Clinical trials of PARPi combination in ovarian cancer with results.
| Trial | Phase | Treatments | Study population | Results | Grade III/IV Aes > 10% | Reference |
|---|---|---|---|---|---|---|
| VEGF inhibitor | ||||||
| NCT03117933 (OCTOVA) | Phase II randomized | Olaparib +/− cediranib vs. weekly paclitaxel | Recurrent platinum-resistant ovarian cancer Prior PARPi allowed (n = 139) |
- O + C vs. O: HR = 0.70; 60% CI = 0.57, 0.86; p = 0.08 - Paclitaxel vs. O: HR = 0.97; 60% CI = 0.79, 1.19; p = 0.55 |
– | Nicum et al. (77) |
| NCT02681237 (EVOLVE) | Phase II | Olaparib + cediranib | Progression on PARPi for recurrent ovarian cancer (n = 34) | ORR 3/34 (9%) SD 20/34 (59%) |
Diarrhea (12%) | Lheureux et al. (61) |
| PIK3CA inhibitor | ||||||
| NCT01623349 | Phase I | Olaparib + alpelisib | Recurrent platinum-resistant ovarian cancer Prior PARPi allowed (n = 28) |
ORR 10/28 (36%) SD 14/28 (50%) |
Hyperglycemia (15%) | Konstantinopoulos et al. (78) |
| ATR inhibitor | ||||||
| NCT03462342 (CAPRI) | Phase II | Olaparib + ceralasertib | Recurrent platinum-sensitive ovarian cancer PARPi pretreated (n = 12) |
ORR 6/12 (50%) | Anemia (15%) Thrombocytopenia (23%) |
Wethington et al. (79) |
| NCT02576444 (OLAPCO) | Phase II | Olaparib + ceralasertib | PARPi-resistant ovarian cancer with HR gene alteration (n = 7) | ORR 1/7 (14%) SD 5/7 (71%) |
1 patient: grade 3 anemia and grade 4 neutropenia | Mahdi et al. (45) |
| WEE1 | ||||||
| NCT03579316 (EFFORT) | Phase II randomized | Adavosertib +/− olaparib | Recurrent ovarian, fallopian tube, or primary peritoneal cancer with progression disease on PARPi (n = 80) | - Cohort A: ORR = 23% PFS = 5.5 months - A+ O = 29% PFS = 6.8 months |
Cohort A: neutropenia (13%); thrombocytopenia (10%) Cohort A/O: thrombocytopenia (20%); neutropenia (15%); diarrhea (12%); fatigue (12%); anemia (10%) |
Westin et al. (80) |
| NCT04197713 (STAR) | Phase Ib | Sequential treatment: adavosertib and olaparib | Patients with mutation in DDR genes or CCNE1 amplified PARPi pretreated (n = 13) |
ORR = 3/12 (25%) SD = 5/12 (42%) |
Hematologic (15%) | Yap et al. (81) |
Aes, adverse effects; n, number of patients; PARPi, polyadenosine diphosphate–ribose polymerase inhibitor; HRD, homologous recombination deficiency; ORR, overall response rate; PFS, progression-free survival; O, olaparib; C, cediranib; A, adavosertib; DDR, deoxyribonucleic acid damage response.