Table 1 Efficacy data for selected studies evaluating PARP inhibitor combinations in advanced solid tumours.

Platinum chemotherapy

Ramalingam et al. (Phase 3) [141]

Carboplatin/paclitaxel +/− veliparib

Previously untreated advanced squamous cell lung cancer (n = 970)

Median PFS: 5.6 mo in both groups (carboplatin/paclitaxel with or without veliparib)

O’Reilly et al. (Phase 2) [142]

Gemcitabine/cisplatin +/− veliparib

Advanced pancreatic adenocarcinoma, germline BRCA1/2 or PALB2 mutation (n = 50)

Median PFS: 10.1 mo (chemo + veliparib) vs 9.7 mo (chemo + placebo)

ORR: 20/27 (74%) with veliparib vs 15/23 (65%) with placebo

Diéras et al. (Phase 3) [143]

Carboplatin/paclitaxel +/− veliparib

BRCA1/2-mutated advanced breast cancer (n = 513)

Median PFS: 14.5 mo (chemo + veliparib) and 12.6 mo (chemo)

DNA alkylators

Pietanza et al. (Phase 2) [144]

Temozolomide +/− veliparib

Previously treated SCLC (n = 104)

PFS at 4 months: 36% (TMZ/veliparib) and 27% (TMZ/placebo)

ORR: 19/49 (39%) for TMZ/veliparib and 6/44 (14%) for TMZ/placebo

Plummer et al. (Phase 2) [136]

Temozolomide + rucaparib

Chemotherapy naive metastatic melanoma (n = 46)

ORR: 8/46 (17%)

Pishvaian et al. (Phase 2) [131]

Temozolomide + velaparib

Treatment-refractory metastatic colorectal cancer (n = 50)

ORR: 2/50 (4%)

Farago et al. (Phase 2) [132]

Temozolomide + olaparib

Previously treated small cell lung cancer (n = 48)

ORR: 20/48 (42%)

Xu et al. (Phase 2) [133]

Temozolomide + olaparib

Metastatic breast cancer (n = 62)

ORR: 7/62 (12%)

Topoisomerase Inhibitors

LoRusso et al. (Phase 1) [138]

Irinotecan + veliparib

Previously treated advanced solid tumours (n = 31)

ORR: 6/31 (19%)

Gorbunova et al. (Phase 2) [145]

5-Fluorouracil/irinotecan +/− veliparib

Untreated metastatic colorectal cancer (n = 130)

Median PFS: 12 mo (FOLFIRI/veliparib) vs 11 mo (FOLFIRI)

Yap et al. (Phase 1) [140]

Sacituzumab + rucaparib

Advanced solid tumours with or without mutations in HR genes (n = 6)

ORR: 3/6 (50%)

Anti-VEGF

Liu et al. (Phase 3) [56]

Olaparib +/− cediranib versus platinum-based chemotherapy

Recurrent platinum-sensitive ovarian cancer (n = 565)

Median PFS: 10.3 mo (chemo), 8.2 mo (olaparib), and 10.4 mo (olaparib/cediranib)

Mirza et al. (Phase 2) [55]

Niraparib +/− bevacizumab

Recurrent platinum-sensitive ovarian cancer (n = 97)

Median PFS: 11.0 mo (niraparib/bevacizumab) and 5.5 mo (niraparib)

Colombo et al. (Phase 2) [57]

Paclitaxel vs cediranib + olaparib (continuous or intermittent)

Recurrent platinum-resistant ovarian cancer (n = 123)

Median PFS: 3.1 mo (paclitaxel), 5.6 mo (continuous cediranib + olaparib), 3.8 mo (intermittent cediranib + olaparib)

Lheureux et al. (Phase 2) [58]

Cediranib + olaparib

Treatment-refractory ovarian cancer with progression on PARPi (n = 34)

ORR: 3/34 (9%)

Lee et al. (Phase 2) [59]

Cediranib + Olaparib

HRD-positive platinum-resistant ovarian cancer (n = 16)

ORR: 8/16 (50%)

Ray-Coquard et al. (Phase 3) [54]

Bevacizumab +/− olaparib maintenance

Ovarian cancer responsive to first-line platinum chemotherapy (n = 806)

Median PFS: 22.1 mo (bevacizumab/olaparib) vs 16.6 mo (bevacizumab)

Hardesty et al. (Phase 2) [146]

Bevacizumab + niraparib maintenance

Ovarian cancer responsive to first-line platinum chemotherapy (n = 105)

Median PFS: 19.6 months

Cecchini et al. (Phase 1/2) [62]

Ramucirumab + olaparib

Refractory metastatic gastric or GEJ adenocarcinoma (n = 46)

ORR: 5/46 (11%)

PI3K/AKT inhibitor

Batalini et al. (Phase 1) [46]

Alpelisib + olaparib

Advanced triple-negative breast cancer and recurrent breast cancer with gBRCA1/2 mutation (n = 17)

ORR: 3/17 (18%)

Konstantinopoulos et al. (Phase 1) [47]

Alpelisib + olaparib

Recurrent ovarian cancer with gBRCA1/2 mutation (n = 28)

ORR: 10/28 (36%)

Yap et al. (Phase 1) [49]

Capivasertib + olaparib

Advanced solid tumours and gBRCA1/2 mutation or BRCA1/2 wild type with DDR or PI3K-AKT pathway alterations (n = 56)

ORR: 19/56 (34%)

Westin et al. (Phase 1) [48]

Capivasertib + olaparib

Recurrent endometrial, ovarian, and triple-negative breast cancer (n = 32)

ORR: 6/32 (19%)

EGFR inhibitor

Stringer-Reasor et al. (Phase 1) [74]

Veliparib + lapatanib

Metastatic triple-negative breast cancer without gBRCA1/2 mutation (n = 17)

ORR: 4/17 (24%)

MEK inhibitor

Kurnit et al. (Phase 1) [65]

Selumetinib + olaparib

Advanced solid tumours with RAS pathway alterations (n = 12)

ORR: 2/12 (17%)

BET inhibitor

Aftimos et al. (Phase 1b/2) [68]

ZEN-3694 + talazoparib

Metastatic triple-negative breast cancer without gBRCA1/2 mutations (n = 50)

ORR: 11/50 (22%)

Immunotherapy

Lee et al. (Phase 1) [83]

Durvalumab + olaparib

Recurrent or metastatic ovarian, breast, cervical, or endometrial cancer (n = 12)

ORR: 2/12 (17%)

Domchek et al, Bang et al., Thomas et al. (Phase 1/2 MEDIOLA) [84, 85, 91]

Durvalumab + olaparib

Advanced germline BRCA-mutated breast cancer and ovarian cancer; metastatic gastric cancer and relapsed SCLC (n = 88)

ORR: 4/39 (10%) in gastric cancer; 19/30 (63%) in gBRCA1/2-mutated breast cancer; 2/19 (11%) in SCLC

Konstantinopoulos et al., Vinayak et al. (Phase 1/2 TOPACIO/KEYNOTE-162) [87, 92]

Niraparib + pembrolizumab

Recurrent platinum-resistant ovarian cancer and advanced TNBC (n = 115)

ORR: 10/60 (18%) in ovarian cancer; 10/55 (18%) in TNBC

Reiss et al. (Phase 1b/2) [93]

Niraparib + ipilimumab or niraparib + nivolumab maintenance after platinum chemotherapy

Advanced platinum-sensitive pancreatic cancer (n = 91)

6-month PFS: 21% with niraparib + nivolumab and 60% with niraparib + ipilimumab

Friedlander et al. (Phase 1) [82]

Pamiparib + tislelizumab

Advanced solid tumours (n = 49)

ORR: 10/49 (20%)

Yap et al. (Phase 1) [94]

Dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab

Advanced solid tumours (n = 35)

ORR: 4/22 (18.2%) with niraparib and 4/13 (30.8%) with niraparib + bevacizumab

ATR inhibitor

Shah et al. (Phase 2) [102]

Ceralasertib + olaparib

Recurrent platinum-resistant, PARPi-naive ovarian cancer (n = 12)

ORR: 0/12 (0%)

Mahdi et al. (Phase 2) [147]

Ceralasertib + olaparib

Advanced solid tumours with deleterious germline or somatic alterations in HR genes (n = 25)

ORR: 2/25 (8.3%)

CHK1 inhibitor

Do et al. (Phase 1) [148]

Prexasertib + olaparib

Advanced solid tumours, ovarian cancer with BRCA1/2 mutation. Previous PARPi allowed (n = 18)

ORR: 4/18 (22%) in patients with BRCA1/2-mutant, PARP inhibitor–resistant ovarian cancer

WEE1 inhibitor

Westin et al. (Phase 2) [111]

Adavosertib +/− olaparib

Recurrent ovarian, fallopian tube, or primary peritoneal cancer with documented progression on PARPi; 48% had germline or somatic BRCA1/2 mutation (n = 35)

ORR: 10/35 (29%) with adavosertib + olaparib vs 8/35 (23%) adavosertib

Yap et al. (Phase 1) [113]

Sequential adavosertib and olaparib

Advanced cancer with actionable DDR variants (n = 12)

ORR: 3/12 (25%)

Antiandrogen

Clarke et al. (Phase 3) [123]

Abirateraone +/− olaparib

Metastatic castration-resistant prostate cancer (n = 796)

Radiographic PFS: 24.8 mo (abiraterone/olaparib) vs 16.6 mo (abiraterone)

Chi et al. (Phase 3) [124]

Abirateraone +/− niraparib

Metastatic castration-resistant prostate cancer (n = 423)

Radiographic PFS in HR-deficient mCRPC: 16.5 mo (abiraterone/niraparib) vs 13.7 mo (abiraterone)