Expected Side Effects of Olaparib
Olaparib causes frequent hematologic and gastrointestinal toxicities, with anemia being the most common dose-limiting adverse effect, occurring in 9-46% of patients depending on severity. 1
Most Common Adverse Events
Hematologic Toxicities (Most Clinically Significant)
- Anemia is the predominant toxicity, occurring in 39-63% of patients at any grade and 17-31% at grade ≥3, often requiring transfusion support 2, 3
- Thrombocytopenia occurs in 20-46% of patients (any grade), with grade ≥3 events in 13-29% 2
- Neutropenia affects 23-26% of patients (any grade), with grade ≥3 events in 6-13% 2
- Lymphopenia occurs in 24% of patients (any grade), with 7% experiencing grade ≥3 events 2
Gastrointestinal Toxicities
- Nausea is extremely common, affecting 53-77% of patients, though typically mild (grade ≥3 in <5%) 2, 3
- Vomiting occurs in 22-40% of patients 2
- Diarrhea affects 34% of patients 2
- Decreased appetite occurs in 20% of patients 2
- Dysgeusia (taste changes) affects 26% of patients 2
- Dyspepsia is reported in ≥20% of patients 4
Constitutional Symptoms
- Fatigue/asthenia is nearly universal, occurring in 53-63% of patients (any grade), with grade ≥3 events in 5-12% 2
- Weight loss is commonly reported 2
Other Common Adverse Events (≥20%)
- Headache 4
- Nasopharyngitis/upper respiratory infections 4
- Cough and dyspnea 2, 3
- Arthralgia/musculoskeletal pain 4
- Back pain 4
- Dermatitis/rash 4
- Abdominal pain/discomfort 4
- Creatinine elevation 2
Rare but Serious Adverse Effects
Life-Threatening Complications
- Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) occurs in approximately 2% of patients—this represents a theoretical but documented risk 2, 4
- Thromboembolic events, including pulmonary emboli 2
- Drug-induced pneumonitis 2
- Life-threatening hemorrhage 5
Treatment Discontinuation and Dose Modifications
- 12-20% of patients discontinue olaparib due to adverse events 2
- Dose reductions are required in approximately 56-75% of patients receiving combination therapy 6
- Dose interruptions occur in approximately 75% of patients on combination regimens 6
- Olaparib increases the risk of dose reduction 3-fold (RR 3.00; 95% CI 1.59-5.70) and treatment discontinuation 2-fold (RR 2.00; 95% CI 1.28-3.14) 3
Combination Therapy Considerations
Olaparib Plus Abiraterone
- The safety profile is consistent with individual drug profiles, with anemia, fatigue/asthenia, and nausea as the most common adverse events 2
- Grade ≥3 adverse events occur in 57% of patients receiving the combination versus 51% with abiraterone alone 2
Talazoparib Plus Enzalutamide (Related PARP Inhibitor for Context)
- Grade ≥3 anemia occurs in 46% of patients—substantially higher than olaparib monotherapy 6
- Thrombocytopenia (8% grade ≥3) and neutropenia (8% grade ≥3) are also significant 2
Mandatory Monitoring Requirements
The NCCN explicitly requires the following monitoring protocol for all patients on olaparib: 2, 1, 7
- Careful monitoring of complete blood counts throughout therapy
- Type and screen availability at all times
- Transfusion support readiness for severe anemia
- Hepatic and renal function monitoring 2
- Intensify CBC monitoring to at least every 2 weeks when combining with skeletal radiation therapy 1
Clinical Pitfalls and Risk Factors
- Longer treatment durations increase anemia risk 3
- Patients with urinary system tumors have higher nausea risk 3
- Patients with breast cancer have higher fatigue risk 3
- Maintenance therapy may be associated with higher fatigue risk compared to active treatment 3
- Patients receiving skeletal radiation should be considered at substantially elevated risk for hematologic toxicity when also receiving olaparib 1