Table 3.
Comparison of toxicities between experimental and control arm in selected randomized trials of DDR-targeting agent combinations.
| Partner Agent | DDR Class | DDR Molecule |
Treatment Arms | Population | Trial Phase | AEs More Frequent with Combination | Ref. | |
|---|---|---|---|---|---|---|---|---|
| Any Grade (Δ ≥ 5%) |
Grade ≥ 3 (Δ ≥ 5%) |
|||||||
| Chemotherapy | PARP-i | Olaparib | Pacli + Ola vs. Plcb + Ola |
Advanced Gastric Cancer | III | Anemia; Diarrhea | Anemia; Neutropenia | [79] |
| Rucaparib | CDDP + Ruca vs. CDDP |
Triple Negative Brest Cancer (Adjuvant) |
II | Fatigue; Nausea | Fatigue; Nausea Neutropenia; Vomiting |
[80] | ||
| Veliparib | CBDCA + VP16 + Veli vs. CBDCA + VP16 |
Small-Cell Lung Cancer | II | Anemia; Fatigue; Headache; Hypokalemia; Hyponatremia; Nausea; Neutropenia; Thrombocytopenia | Anemia; Febrile neutropenia; Hypokalemia; Hyponatremia; Neutropenia; Thrombocytopenia | [81] | ||
| CDDP + Gem + Veli CDDP + Gem + Plcb |
Stage III-IV Pancreatic Carcinoma gBRCA/PALB2 mut |
II * | Nausea | Anemia; Neutropenia; Thrombocytopenia | [82] | |||
| mFOLFIRI + Veli vs. FOLFIRI |
Advanced Pancreatic Carcinoma | II | NR | Dehydration; Diarrhea; Fatigue; Nausea; Neutropenia; Vomiting | [83] | |||
| CBDCA + Pacli + Veli vs. CBDCA + Pacli + Plcb |
Epithelial Ovarian Cancer (First Line) |
III | Anemia; Constipation; Insomnia; Neutropenia; Thrombocytopenia | Anemia; Neutropenia; Thrombocytopenia | [33] | |||
| CBDCA + Pacli + Veli vs. CBDCA + Pacli + Plcb |
Triple Negative Brest Cancer (Neoadjuvant) |
III | Diarrhea; Nausea; Neutropenia; Stomatitis; Thrombocytopenia; Vomiting | Anemia | [84] | |||
| CBDCA + Pacli + Veli vs. CBDCA + Pacli + Plcb |
Advanced Triple Negative Brest Cancer gBRCA mut |
III | Anemia; Back pain; Cough; Diarrhea; Hypomagnesemia; Nausea; Peripheral edema | Thrombocytopenia | [85] | |||
| CBDCA + Pacli + Veli vs. CBDCA + Pacli + Plcb |
Advanced Squamous NSCLC | III | No differences ≥5% | No differences ≥5% | [86] | |||
| ATR-i | Berzosertib | CDDP + Gem + Berzo vs. CDDP + Gem |
Urothelial Cancer | II | Emesis; Fatigue; Peripheral edema |
Neutropenia; Thrombocytopenia |
[87] | |
| Gem + Berzo vs. Gem |
Platinum Resistant Ovarian Cancer |
II | Anemia; AST/ALT increase; Headache; Nausea; Neutropenia; Thrombocytopenia; Vomiting |
Neutropenia; Thrombocytopenia |
[21] | |||
| WEE1-i | Adavosertib | Gem + Ada vs. Gem+ Plcb |
Platinum Resistant Ovarian Cancer |
II | Abdominal painAlopecia; Diarrhea; Constipation; Fatigue; Fever; Hypertension; Hypokalemia; Hypomagnesemia; Hyponatremia Insomnia; Nausea; Neutropenia; Thrombocytopenia; Vomiting |
Anemia; Febrile neutropenia; Hypertension; Hypokalemia; Hypomagnesemia; Neutropenia; Rash Thrombocytopenia; Vomiting |
[77] | |
| CBDCA + Pacli + Ada vs. CBDCA + Pacli + Plcb |
Platinum Sensitive Ovarian Cancer TP53 mut |
II | Abdominal pain; Anemia Constipation; Diarrhea; Dyspnea; Myalgia; Nausea; Neutropenia Thrombocytopenia; Vomiting |
Anemia, Diarrhea; Febrile Neutropenia; Neutropenia; Thrombocytopenia; Vomiting | [24] | |||
| Anti--angiogenics | PARP-i | Niraparib | Beva + Nira vs. Nira |
Platinum Sensitive Ovarian Cancer |
II | Anemia; Anorexia; Cough; Headache; Hypertension; Myalgia; Nausea; Proteinuria; Vomiting | Hypertension | [88] |
| Olaparib | Beva + Ola vs. Beva + Plcb |
Platinum Sensitive Ovarian Cancer |
III | Anemia; Fatigue; Hypertension; Nausea; Thrombocytopenia; Vomiting | Anemia | [16] | ||
| Cedi + Ola vs. Ola |
Platinum Resistan Ovarian Cancer |
II | Abdominal pain; Anorexia; Constipation; Diarrhea; Fatigue; Headache; Hypertension; Hypothyroidism; Mucositis; Proteinuria; Thrombocytopenia | Diarrhea; Fatigue; Hypertension |
[89] | |||
* Two-arm non-comparative trial. Table Legend: Δ differential incidence between experimental and control arm; Ada: adavosertib; Berzo: berzosertib; Beva: bevacizumab; CBDCA: carboplatin; CDDP: cisplatin; Cedi: cediranib; DDR: DNA damage response; FOLFIRI: folinic acid, 5-fluorouraicil and irinotecan; gBRCA/PALB2: germline BRCA/PALB2; Gem: gemcitabine; -i: inhibitors; Mut: mutated; Nira: niraparib; NA: not applicable; NR: not reported; NSCLC: non-small cell lung cancer; Ola: olaparib; Pacli: paclitaxel; Pclb: placebo; Ref: reference; Veli: veliparib; VP16: etoposide.