Drug Monograph
Lynparza (Olaparib)
olaparib
Pharmacokinetic Profile
Half-Life
14.9 ± 8.2 hours
Metabolism
CYP3A4/5 (primary)
Protein Binding
~82%
Bioavailability
High (tablet formulation; food has no clinically significant effect)
Volume of Distribution
158 ± 136 L
Clinical Information
Drug Class
Poly (ADP-ribose) Polymerase (PARP) Inhibitor
Available Doses
100 mg & 150 mg tablets
Route
Oral
Renal Adjustment
Moderate (CrCl 31–50): reduce to 200 mg BID; severe: not studied
Hepatic Adjustment
None for mild/moderate (Child-Pugh A, B); no data for severe (C)
Pregnancy
Contraindicated — teratogenic & embryo-fetal toxicity
Lactation
Do not breastfeed during treatment or for 1 month after last dose
Schedule / Legal Status
Rx Only (not a controlled substance)
Generic Available
No
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| BRCAm advanced ovarian cancer — 1st-line maintenance | Adults with gBRCAm or sBRCAm in CR/PR to 1st-line platinum chemo | Monotherapy (up to 2 years) | FDA Approved |
| HRD-positive advanced ovarian cancer — 1st-line maintenance with bevacizumab | Adults with HRD-positive status (BRCAm and/or genomic instability) in CR/PR to 1st-line platinum chemo | Combination with bevacizumab (up to 2 years) | FDA Approved |
| BRCAm recurrent ovarian cancer — maintenance | Adults with gBRCAm or sBRCAm recurrent disease in CR/PR to platinum chemo | Monotherapy | FDA Approved |
| gBRCAm HER2-negative high-risk early breast cancer — adjuvant | Adults treated with neoadjuvant or adjuvant chemo | Monotherapy (1 year) | FDA Approved |
| gBRCAm HER2-negative metastatic breast cancer | Adults treated with prior chemo; HR+ patients must have had prior endocrine therapy | Monotherapy | FDA Approved |
| gBRCAm metastatic pancreatic adenocarcinoma — 1st-line maintenance | Adults not progressed on ≥16 weeks of 1st-line platinum-based chemo | Monotherapy | FDA Approved |
| HRR gene-mutated mCRPC — monotherapy | Adults who progressed following enzalutamide or abiraterone | Monotherapy + GnRH analog | FDA Approved |
| BRCAm mCRPC — combination with abiraterone | Adults with BRCAm mCRPC | Combination with abiraterone + prednisone/prednisolone + GnRH analog | FDA Approved |
Olaparib is the first-in-class PARP inhibitor approved for clinical use and currently holds the broadest set of indications among all PARP inhibitors, spanning ovarian, breast, pancreatic, and prostate cancers. All indications require companion diagnostic testing to confirm the relevant biomarker (BRCA mutation, HRR gene mutation, or HRD-positive status) before initiating therapy (FDA PI). The capsule formulation (NDA 206162) was voluntarily withdrawn by AstraZeneca in March 2024 following the SOLO3 trial results; only the tablet formulation (NDA 208558) remains commercially available.
Dosing
Primary Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| BRCAm advanced ovarian — 1st-line maintenance | 300 mg BID | 300 mg BID | 600 mg/day | Continue up to 2 years. Stop if complete response at 2 years; may continue beyond 2 years if disease persists and clinician judges ongoing benefit. SOLO-1 trial setting |
| HRD+ advanced ovarian — 1st-line maintenance + bevacizumab | 300 mg BID | 300 mg BID | 600 mg/day | Bevacizumab 15 mg/kg IV q3w for total 15 months. Continue olaparib up to 2 years. PAOLA-1 trial setting |
| BRCAm recurrent ovarian — maintenance | 300 mg BID | 300 mg BID | 600 mg/day | Continue until disease progression or unacceptable toxicity. SOLO-2 trial setting |
| gBRCAm HER2– high-risk early breast — adjuvant | 300 mg BID | 300 mg BID | 600 mg/day | Treat for total of 1 year. HR+ patients continue concurrent endocrine therapy. OlympiA trial setting |
| gBRCAm HER2– metastatic breast cancer | 300 mg BID | 300 mg BID | 600 mg/day | Continue until progression or unacceptable toxicity. OlympiAD trial setting |
| gBRCAm metastatic pancreatic — 1st-line maintenance | 300 mg BID | 300 mg BID | 600 mg/day | Patient must not have progressed on ≥16 weeks of 1st-line platinum chemo. POLO trial setting |
| HRR-mutated mCRPC — after enzalutamide or abiraterone | 300 mg BID | 300 mg BID | 600 mg/day | Continue GnRH analog or prior bilateral orchiectomy. Treat until progression or unacceptable toxicity. PROfound trial setting |
| BRCAm mCRPC — with abiraterone + prednisone | 300 mg BID | 300 mg BID | 600 mg/day | Abiraterone 1,000 mg daily + prednisone/prednisolone 5 mg BID. Continue GnRH analog. PROpel trial setting |
Dose Modifications
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Adverse reaction management (1st reduction) | 250 mg BID | 250 mg BID | 500 mg/day | Consider treatment interruption first; reduce if adverse reaction recurs or persists |
| Adverse reaction management (2nd reduction) | 200 mg BID | 200 mg BID | 400 mg/day | Minimum dose; discontinue if further reduction required |
| Concurrent strong CYP3A inhibitor | 100 mg BID | 100 mg BID | 200 mg/day | Avoid combination if possible. Resume prior dose 3–5 half-lives after inhibitor discontinued. |
| Concurrent moderate CYP3A inhibitor | 150 mg BID | 150 mg BID | 300 mg/day | Avoid combination if possible. Avoid grapefruit and Seville oranges. |
| Moderate renal impairment (CrCl 31–50 mL/min) | 200 mg BID | 200 mg BID | 400 mg/day | Mild renal impairment (CrCl 51–80): no adjustment. Severe (≤30): not studied. |
Clinical Pearl: Uniform Dose Across All Indications
Unlike many oncology agents, olaparib uses the same starting dose of 300 mg BID for all eight indications. What varies is the treatment duration and stopping rules: ovarian first-line maintenance has a 2-year cap (with extension possible); early breast cancer adjuvant is 1 year; all other indications continue until progression. Tablets should be swallowed whole without crushing or chewing, and can be taken with or without food.
Pharmacology
Mechanism of Action
Olaparib is a potent inhibitor of PARP-1, PARP-2, and PARP-3 enzymes, which play essential roles in single-strand DNA break repair via the base excision repair pathway. By blocking PARP activity, olaparib forces cells to rely on homologous recombination repair (HRR) for double-strand break resolution. In tumour cells with defective HRR machinery (such as those carrying BRCA1/2, ATM, PALB2, or other HRR gene mutations), this results in synthetic lethality: the accumulation of unrepaired double-strand breaks leads to genomic instability and cell death. Beyond catalytic inhibition, olaparib traps PARP-DNA complexes at sites of damage, creating cytotoxic lesions that further compromise replication forks. In prostate cancer models, PARP-1 also contributes to androgen receptor transcriptional activity, providing mechanistic rationale for combining olaparib with androgen receptor pathway inhibitors.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Median Tmax 1.5 h; high-fat meal delays Tmax by 2.5 h but does not meaningfully change AUC (~8% increase); AUC accumulation ratio 1.8 at steady state | Can be taken with or without food; rapid absorption supports twice-daily dosing schedule |
| Distribution | Vd 158 ± 136 L; protein binding ~82% | Extensive tissue distribution; moderate protein binding reduces displacement-interaction risk |
| Metabolism | CYP3A4/5 primary; parent drug accounts for 70% of circulating radioactivity; oxidative metabolism with subsequent glucuronidation/sulfation | Highly susceptible to CYP3A modulation: strong inhibitor increases AUC 2.7-fold, strong inducer decreases AUC by 87% (FDA PI) |
| Elimination | t½ 14.9 ± 8.2 h; CL/F 7.4 ± 3.9 L/h; 44% urine, 42% feces (mostly as metabolites); 86% recovered within 7 days | Moderate half-life supports BID dosing; balanced renal-fecal excretion; moderate renal impairment requires dose reduction to 200 mg BID |
Side Effects
Adverse reaction data are from the pooled single-agent safety population (N = 2,901 across multiple trials) and from the July 2025 FDA prescribing information. Rates reflect the olaparib arm unless otherwise specified. Incidence ranges represent variation across pivotal trials.
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nausea | 60% | Most common adverse reaction; usually Grade 1–2; anti-emetics and taking with food may help; tends to improve over first few weeks |
| Fatigue / asthenia | 55% | Dose-limiting in some patients; consider dose reduction to 250 mg BID |
| Anaemia | 36% | Most clinically significant haematological toxicity; Grade ≥3 in ~18–22% across trials; transfusion may be needed; monitor CBC monthly (FDA PI) |
| Vomiting | 32% | Often accompanies nausea; generally manageable with anti-emetics |
| Diarrhoea | 24% | Usually Grade 1–2; manage with loperamide if persistent |
| Decreased appetite | 22% | Monitor weight and nutritional status; may contribute to treatment discontinuation |
| Headache | 16% | Usually mild; assess for other causes if severe or persistent |
| Dysgeusia | 15% | Altered taste; may compound appetite loss |
| Cough | 15% | If new or worsening, rule out pneumonitis (reported in 1.0% of patients) |
| Neutropenia | 14% | Grade ≥3 in ~5–7%; monitor CBC monthly |
| Dyspnoea | 14% | Evaluate for anaemia, PE (VTE 8% in mCRPC), and pneumonitis |
| Dizziness | 12% | Caution with driving; assess for anaemia contribution |
| Dyspepsia | 12% | Taking with food may reduce GI symptoms |
| Leukopenia | 11% | Monitor with monthly CBC alongside neutrophil and platelet counts |
| Thrombocytopenia | 10% | Grade ≥3 in ~3–4%; assess bleeding risk especially in mCRPC patients on anticoagulants |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Stomatitis / oral mucositis | 5–9% | Maintain oral hygiene; may require treatment interruption if severe |
| Abdominal pain | 5–8% | Evaluate for disease progression if significant upper abdominal pain in pancreatic cancer patients |
| Urinary tract infection | 5–14% | Higher with bevacizumab combination (PAOLA-1: 14%); routine urinalysis if symptomatic |
| Lymphopenia | 5–10% | Higher with combination regimens; monitor CBC monthly |
| Mean corpuscular volume increase | ~50% (lab abnormality) | Elevated MCV is characteristic of PARP inhibitors and does not require B12/folate workup unless clinical suspicion exists |
| Rash / dermatitis | 1–5% | Post-marketing: hypersensitivity including angioedema and erythema nodosum reported |
| Elevated creatinine | ~30% (lab abnormality) | Olaparib inhibits renal transporters (OCT2, MATE1/2K); rise is usually not reflective of true GFR decline |
Serious
Serious Adverse Effects (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Myelodysplastic syndrome / Acute myeloid leukaemia (MDS/AML) | ~1.2% (26/2,219); majority fatal | Median ~2 years (range <6 months to >4 years) | Discontinue olaparib if MDS/AML confirmed. Monitor CBC at baseline and monthly. Refer to haematology for prolonged cytopenias not recovering after 4 weeks (FDA PI) |
| Pneumonitis (including fatal cases) | 1.0% (29/2,851) | Variable | Interrupt olaparib if suspected; discontinue if confirmed. Assess with imaging and treat appropriately (FDA PI) |
| Venous thromboembolism (VTE) including pulmonary embolism | 8% in mCRPC (PE 6%) vs 2.5% placebo | Any time during treatment | Monitor for signs of VTE/PE; treat with anticoagulation as appropriate; highest risk in mCRPC population (FDA PI) |
| Hepatotoxicity including drug-induced liver injury (DILI) | Uncommon (post-marketing + recent labeling update July 2025) | Variable | Monitor bilirubin and transaminases at baseline and throughout treatment. If DILI suspected, withhold olaparib; discontinue if confirmed (FDA PI) |
| Severe anaemia requiring transfusion | Grade ≥3: 18–22% | Weeks to months | Interrupt treatment until Hb recovers to ≥ Grade 1; dose reduce upon resumption. If not recovering after 4 weeks, refer to haematology and consider bone marrow biopsy (FDA PI) |
Discontinuation
Discontinuation Rates
SOLO-1 (Ovarian 1st-line)
12%
Top reasons: Fatigue (3.1%), anaemia (2.3%), nausea (2.3%)
OlympiA (Breast adjuvant)
10.8%
Top reasons: Anaemia, nausea, fatigue
| Trial / Setting | Discontinuation Rate | Context |
|---|---|---|
| SOLO-1 (BRCAm ovarian 1st-line) | 12% | Median treatment 25 months; dose interruptions 52%, dose reductions 28% |
| SOLO-2 (BRCAm recurrent ovarian) | 11% | Anaemia most common reason for interruption |
| OlympiA (gBRCAm breast adjuvant) | 10.8% | 1-year fixed treatment duration |
| PROfound (HRR-mutated mCRPC) | 18% | Higher rate reflects pretreated, mCRPC population |
Managing Anaemia — The Key Haematological Toxicity
Anaemia is the most clinically significant adverse effect of olaparib and the most common reason for dose interruption across all trials. In SOLO-1, anaemia led to dose interruption in 23% of patients. Monthly CBC monitoring is mandatory. If haemoglobin has not recovered to Grade 1 or less after 4 weeks of treatment interruption, refer to haematology for bone marrow analysis and cytogenetics to exclude MDS/AML. Note that elevated MCV is an expected pharmacological effect of PARP inhibition and does not indicate B12 or folate deficiency in most cases.
Drug Interactions
Olaparib is predominantly metabolised by CYP3A4/5, making it highly susceptible to CYP3A modulators. It is also a weak net CYP3A inhibitor and an inhibitor of multiple drug transporters (BCRP, OATP1B1, OCT1, OCT2, OAT3, MATE1, MATE2K, UGT1A1), creating potential to affect the disposition of co-administered substrates.
MajorStrong CYP3A inhibitors (e.g., itraconazole, ketoconazole, ritonavir)
MechanismCYP3A4 inhibition increases olaparib AUC by 170% and Cmax by 42%
EffectNearly 3-fold increase in exposure; substantially increased toxicity risk
ManagementAvoid combination. If unavoidable, reduce olaparib to 100 mg BID. Resume prior dose 3–5 half-lives after inhibitor is discontinued
FDA PIMajorStrong CYP3A inducers (e.g., rifampicin, phenytoin, carbamazepine)
MechanismCYP3A4 induction decreases olaparib AUC by 87% and Cmax by 71%
EffectNear-complete loss of olaparib efficacy
ManagementAvoid combination; no dose increase can compensate for 87% AUC reduction
FDA PIModerateModerate CYP3A inhibitors (e.g., fluconazole, erythromycin, diltiazem, verapamil)
MechanismPredicted to increase olaparib AUC by ~121%
EffectApproximately doubled exposure; increased haematological toxicity risk
ManagementAvoid if possible. If unavoidable, reduce olaparib to 150 mg BID. Also avoid grapefruit and Seville oranges
FDA PIModerateModerate CYP3A inducers (e.g., efavirenz, bosentan)
MechanismPredicted to decrease olaparib AUC by ~60%
EffectSubstantially reduced olaparib efficacy
ManagementAvoid combination; no dose adjustment is recommended as compensation is insufficient
FDA PIModerateMyelosuppressive anticancer agents
MechanismAdditive myelosuppression when combined with DNA-damaging agents or other myelosuppressive therapies
EffectPotentiation and prolongation of myelosuppressive toxicity
ManagementDo not use olaparib concurrently with other myelosuppressive chemo unless specifically indicated. Monitor CBC closely
FDA PIMinorNarrow TI CYP3A substrates (e.g., cyclosporine, tacrolimus)
MechanismOlaparib is a weak net CYP3A inhibitor (~1.6-fold midazolam AUC increase predicted)
EffectModest increase in CYP3A substrate exposure; clinically relevant for narrow TI drugs
ManagementMonitor levels of narrow TI CYP3A substrates; no effect on anastrozole/letrozole exposure
FDA PIMonitoring
- CBC with differentialBaseline, then monthly
RoutineCritical for detecting anaemia (36%), neutropenia (14%), thrombocytopenia (10%), and early signs of MDS/AML. If cytopenias persist >4 weeks despite treatment interruption, refer to haematology for bone marrow analysis and cytogenetics (FDA PI). - Hepatic function (LFTs)Baseline, then periodically
RoutineJuly 2025 label update added hepatotoxicity including DILI as a warning. Monitor bilirubin and transaminases at baseline and throughout treatment. Withhold if DILI suspected; discontinue if confirmed (FDA PI). - Renal functionBaseline, then periodically
RoutineOlaparib inhibits renal transporters (OCT2, MATE1/2K), causing up to 30% creatinine elevation that does not reflect true GFR decline. Use CrCl to guide dose adjustment: reduce to 200 mg BID for CrCl 31–50 mL/min. - Pregnancy statusBefore initiating treatment
RoutineVerify pregnancy status in females of reproductive potential. Olaparib is teratogenic at exposures below the human dose. Effective contraception required during treatment and for 6 months (females) or 3 months (males) after last dose (FDA PI). - Respiratory symptomsAt each visit
Trigger-basedNew or worsening dyspnoea, cough, or fever should prompt evaluation for pneumonitis (1.0%, some fatal). Interrupt olaparib pending assessment; discontinue if pneumonitis confirmed (FDA PI). - VTE signs/symptoms (mCRPC)At each visit
Trigger-basedVTE occurred in 8% of mCRPC patients (PE in 6% vs 1.5% placebo). Monitor for leg swelling, chest pain, and dyspnoea. Consider prophylactic anticoagulation in high-risk patients (FDA PI). - Biomarker confirmationBefore initiating treatment
RoutineAll indications require FDA-approved companion diagnostic testing to confirm BRCA mutation, HRR gene mutation, or HRD-positive status. Sample types vary by indication (tumour, blood, or plasma ctDNA).
Contraindications & Cautions
Absolute Contraindications
- Pregnancy: Olaparib causes teratogenicity and embryo-fetal toxicity at exposures below the human therapeutic dose. Effective contraception is mandatory during treatment and for 6 months (females) or 3 months (males) after the last dose (FDA PI).
The FDA prescribing information states no absolute contraindications in Section 4. However, the embryo-fetal toxicity risk functionally precludes use in pregnancy.
Relative Contraindications (Specialist Input Recommended)
- Pre-existing significant cytopenias: Do not start olaparib until patients have recovered from haematological toxicity caused by previous chemotherapy (≤Grade 1). Patients with baseline anaemia, neutropenia, or thrombocytopenia may be at heightened risk for severe myelosuppression.
- History of MDS/AML or pre-malignant haematological conditions: Olaparib carries a 1.2% incidence of MDS/AML with the majority of events being fatal. All affected patients had received prior platinum-based chemotherapy or radiotherapy.
- Severe renal impairment (CrCl ≤30 mL/min) or end-stage renal disease: Not studied; use at clinician’s discretion with close monitoring.
- Severe hepatic impairment (Child-Pugh C): No data available.
Use with Caution
- Concurrent strong/moderate CYP3A inhibitors or inducers: Inhibitors increase exposure up to 2.7-fold; inducers can reduce efficacy by up to 87%. Dose adjustments are mandated for inhibitors; inducers should be avoided entirely.
- Patients with mCRPC: VTE risk is significantly elevated (8% vs 2.5% placebo), including PE in 6%. Thromboprophylaxis should be considered.
- Lactating women: No data on presence in human milk. Breastfeeding is contraindicated during treatment and for 1 month after the last dose.
FDA Safety Communication
MDS/AML, Pneumonitis, VTE, and Hepatotoxicity
Olaparib carries warnings for MDS/AML (~1.2%, majority fatal; median onset ~2 years), pneumonitis (1.0%, some fatal), venous thromboembolism (8% in mCRPC including 6% PE), and hepatotoxicity including DILI (July 2025 labeling update). Monthly CBC monitoring is mandatory. MDS/AML requires permanent discontinuation. Pneumonitis requires treatment interruption and discontinuation if confirmed. Patients should be monitored for liver function abnormalities throughout therapy.
Patient Counselling
Purpose of Therapy
Olaparib works by blocking a DNA repair enzyme called PARP. Cancer cells with specific genetic mutations (such as BRCA1/2) cannot repair their DNA effectively when PARP is blocked, leading to cancer cell death. Depending on the type and stage of cancer, olaparib may be used as maintenance therapy after chemotherapy to delay cancer from coming back, as treatment for advanced cancer, or as adjuvant therapy after surgery and chemotherapy to reduce the risk of recurrence.
How to Take
Take two 150 mg tablets (300 mg total) twice daily, approximately 12 hours apart, with or without food. Swallow tablets whole; do not crush, chew, dissolve, or split. If a dose is missed, skip it and take the next dose at the scheduled time. Do not double up on doses.
Nausea & Vomiting
Tell patientNausea is the most common side effect (about 6 in 10 patients) and usually improves over the first few weeks. Taking olaparib with a light snack may help. Anti-nausea medication can be prescribed if needed.
Call prescriberIf vomiting is persistent or prevents keeping olaparib down, or if unable to eat or drink for more than 24 hours.
Anaemia & Blood Count Changes
Tell patientOlaparib can lower red blood cells, white blood cells, and platelets. Blood tests will be done monthly to monitor these counts. Fatigue, shortness of breath, or paleness may be signs of anaemia. Sometimes blood transfusions are needed.
Call prescriberIf experiencing significant weakness, breathlessness, unusual bruising or bleeding, fever, or signs of infection.
Breathing Problems
Tell patientIn rare cases, olaparib can cause lung inflammation (pneumonitis) which can be serious. A new or worsening cough, shortness of breath, or fever should be reported promptly.
Call prescriberImmediately if experiencing new or worsening shortness of breath, persistent cough, or fever while on olaparib.
Blood Clots (mCRPC patients)
Tell patientPatients with prostate cancer have an increased risk of blood clots in the legs or lungs while taking olaparib. Know the warning signs: leg swelling, redness or pain in the calf, sudden chest pain, or difficulty breathing.
Call prescriberSeek emergency care immediately if experiencing sudden chest pain, shortness of breath, or significant leg swelling.
Contraception & Pregnancy
Tell patientOlaparib can cause serious birth defects. Women who could become pregnant must use effective contraception during treatment and for 6 months after the last dose. Male patients with female partners who could become pregnant must use contraception during treatment and for 3 months after. Breastfeeding is not safe during treatment and for 1 month afterward.
Call prescriberIf pregnancy is suspected during treatment or within the contraception period.
Drug Interactions
Tell patientMany medications can interact with olaparib, either increasing its side effects or reducing its effectiveness. This includes some antibiotics, antifungals, HIV medications, and anti-seizure drugs. Avoid grapefruit and Seville oranges. Always inform every healthcare provider about olaparib use before starting any new medication.
Call prescriberBefore starting or stopping any medication, including over-the-counter drugs and herbal supplements.
Sources
Regulatory (PI / SmPC)
- Lynparza (olaparib) prescribing information. AstraZeneca Pharmaceuticals LP. Revised July 2025. DailyMedPrimary regulatory source for all dosing, safety, pharmacokinetic, and drug interaction data cited in this monograph.
Key Clinical Trials
- Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495–2505. doi:10.1056/NEJMoa1810858SOLO-1 trial — established olaparib as first-line maintenance in BRCAm advanced ovarian cancer with significant PFS benefit (HR 0.30).
- Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416–2428. doi:10.1056/NEJMoa1911361PAOLA-1 trial — supported the olaparib + bevacizumab combination in HRD-positive advanced ovarian cancer.
- 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). Lancet Oncol. 2017;18(9):1274–1284. doi:10.1016/S1470-2045(17)30469-2SOLO-2 trial — demonstrated PFS benefit in BRCAm platinum-sensitive recurrent ovarian cancer.
- Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394–2405. doi:10.1056/NEJMoa2105215OlympiA trial — established adjuvant olaparib in gBRCAm HER2-negative high-risk early breast cancer with iDFS benefit.
- 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(6):523–533. doi:10.1056/NEJMoa1706450OlympiAD trial — demonstrated PFS benefit of olaparib vs chemotherapy in gBRCAm metastatic breast cancer.
- Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381(4):317–327. doi:10.1056/NEJMoa1903387POLO trial — first phase 3 evidence for PARP inhibitor maintenance in gBRCAm metastatic pancreatic cancer.
- de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382(22):2091–2102. doi:10.1056/NEJMoa1911440PROfound trial — established olaparib in HRR gene-mutated mCRPC post-enzalutamide/abiraterone.
- Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. NEJM Evid. 2022;1(9):EVIDoa2200043. doi:10.1056/EVIDoa2200043PROpel trial — supported the olaparib + abiraterone combination in BRCAm mCRPC.
Mechanistic / Basic Science
- Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434(7035):913–917. doi:10.1038/nature03443Landmark paper establishing the synthetic lethality concept between PARP inhibition and BRCA deficiency.
- Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–921. doi:10.1038/nature03445Companion landmark paper independently confirming PARP inhibitor synthetic lethality in BRCA-deficient cells.
Pharmacokinetics / Special Populations
- Pilla Reddy V, Lukacova V, Owen J, et al. Physiologically based pharmacokinetic modeling for olaparib dosing recommendations: bridging formulations, drug interactions, and patient populations. Clin Pharmacol Ther. 2019;105(6):1444–1453. doi:10.1002/cpt.1103PBPK model supporting dose adjustments for CYP3A modulators, renal impairment, and hepatic impairment.
- Moore K, Colombo N, Scambia G, et al. Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer: updated overall survival. Lancet Oncol. 2022;23(3):386–396. doi:10.1016/S1470-2045(22)00056-4SOLO-1 long-term OS update confirming durable survival benefit in BRCAm ovarian cancer.