Currently-approved PARP inhibitors carry a similar overall safety profile, with a class effect noted for all grade nausea/vomiting, grade ≥3 anaemia, and grade ≥3 fatigue [1, 2]. Among the most common adverse events associated with PARP inhibitor treatment in clinical trials were fatigue, anaemia, neutropenia, thrombocytopenia, nausea, vomiting, diarrhoea, headache, and decreased appetite [3-9]. Some of these toxicities had a high incidence in the placebo arms of the randomized trials as well.
Many of the grade ≥3 events initially reported with PARP inhibition resolved after the first months of treatment, although the incidence of grade 3 fatigue/asthenia was found sometimes found to increase through treatment [2, 10].
Although discontinuation from PARP inhibitors is uncommon, many patients do require dose reductions; however, the impact of dose reductions on efficacy is not clear as there has been conflicting data to date [2].
There are also some drug-specific differences between PARP inhibitors to be aware of. Rucaparib is associated with increased incidence of laboratory abnormalities (elevated ALT, AST, and creatinine) [1, 5], and relatively high incidences of thrombocytopenia and hypertension have been observed with niraparib [1, 7].
Table 3: Summary of class effects associated with PARP inhibitor treatment and their management* [1, 2]
Fatigue | ||
|---|---|---|
Severity |
Management |
Proactive |
1 to ≥3 |
• Exclude anaemia |
Conserving energy |
Other |
Similar levels to that observed for chemotherapy |
|
Haematological toxicity | ||
Severity |
Management |
Proactive |
1 or 2 common; 3 uncommon |
• Mild-moderate anaemia – transfusions or other standards of care |
Ensure baseline values are in normal range or grade 1: |
Drug |
Olaparib/rucaparib/ talazoparib: anaemia> thrombocytopenia & neutropenia |
|
Other |
Grade ≥3 haematological toxicities are the most common AE leading to dose modification |
|
Nausea and vomiting | ||
Severity |
Management |
Proactive |
Mild to moderate |
• Prescribe antiemetic regimen as needed |
Counsel about risk |
Other |
Most common during first month |
|
*AE management will depend on the grade. This table provides practical suggestions for AE management, but in the clinic the approach should be tailored to the patient and the severity of the AE.
You can find out more about specific aspects of PARP inhibitor safety by clicking on the links below the reference list.
References
- LaFargue CJ, Dal Molin GZ, Sood AK, Coleman RL. Exploring and comparing adverse events between PARP inhibitors. Lancet Oncol 2019; 20: e15-e28.
- Paluch-Shimon S. Managing side effects of PARP inhibitors. In ESMO 2018 Congress. Munich, Germany 2018.
- Litton JK, Rugo HS, Ettl J et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753-763.
- Robson M, Im SA, Senkus E et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523-533.
- Coleman RL, Oza AM, Lorusso D et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 390: 1949-1961.
- Ledermann J, Harter P, Gourley C et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 2014; 15: 852-861.
- Mirza MR, Monk BJ, Herrstedt J et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med 2016; 375: 2154-2164.
- Pujade-Lauraine E, Ledermann JA, Selle F et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18: 1274-1284.
- Moore K, Colombo N, Scambia G et al. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 2018; 379.
- Friedlander M, Matulonis U, Gourley C et al. Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy. Br J Cancer 2018; 119: 1075-1085.