Last updated: June 23, 2026
Lynparza (olaparib, AZD2281) is an oral PARP1/2 inhibitor developed by AstraZeneca and co-marketed with Merck. It was the first PARP inhibitor approved by the FDA (December 2014, BRCA-mutated advanced ovarian cancer) and has the broadest indication map of any PARP inhibitor — FDA-approved across four cancer types (ovarian, HER2-negative gBRCA breast, HRR-mutated mCRPC, gBRCA metastatic pancreatic maintenance).
Mechanism of action:Olaparib inhibits PARP1 and PARP2, enzymes that repair single-strand DNA breaks. In tumors that have lost the homologous recombination (HR) double-strand break repair pathway — typically because of BRCA1, BRCA2, or other HR-pathway mutations — unrepaired single-strand breaks are converted into lethal double-strand breaks. This synthetic-lethal interaction selectively kills HR-deficient tumor cells while sparing most normal cells. See the PARP inhibitor mechanism hub for the broader class context.
Regulatory status:FDA-approved across 4 cancer types and 8 distinct labels. Pivotal trials: SOLO-1 (ovarian 1L maintenance BRCA), PAOLA-1 (ovarian 1L maintenance + bevacizumab HRD+), SOLO-2 (recurrent ovarian maintenance), OlympiA (adjuvant breast gBRCA), OlympiAD (metastatic breast gBRCA), PROfound (mCRPC HRR), PROpel (1L mCRPC + abiraterone), POLO (pancreatic gBRCA maintenance).
Every cell has two main ways to fix broken DNA: a fast, sloppy patch for single-strand breaks (where PARP1 and PARP2 are central), and a slow, accurate repair for the more dangerous double-strand breaks (where BRCA1 and BRCA2 are central).
Some cancer cells have lost the BRCA-driven repair pathway, often because of an inherited (germline) or acquired (somatic) mutation. These cancer cells survive only because they can still rely on the PARP-driven single-strand patch. Lynparza takes away that fallback. With both pathways disabled, the cancer cells accumulate unfixable DNA damage and die, while most normal cells — which still have functional BRCA-pathway repair — are largely spared. This selective vulnerability is called synthetic lethality.
The patients most likely to benefit are those whose tumor has a BRCA1, BRCA2, or other homologous-recombination repair (HRR) gene mutation, or a tumor with broader HRD (homologous recombination deficiency) as measured by an FDA-cleared companion diagnostic. Knowing your BRCA/HRR/HRD status is the first step in deciding whether Lynparza or another PARP inhibitor is a good option.
Lynparza has accumulated 8 FDA approvals across 4 cancer types since the December 2014 first-in-class ovarian approval. The pivotal trial, FDA decision date, and biomarker setting are listed for each.
1L maintenance, BRCA-mutated advanced ovarian (post-platinum response)
1L maintenance + bevacizumab, HRD-positive advanced ovarian
Maintenance, BRCA-mutated platinum-sensitive recurrent ovarian
Adjuvant treatment of high-risk HER2-negative gBRCA early breast cancer
HER2-negative gBRCA metastatic breast cancer (after prior chemotherapy)
HRR-mutated metastatic castration-resistant prostate cancer (mCRPC), monotherapy after prior new hormonal therapy
1L mCRPC in combination with abiraterone + prednisone
Maintenance therapy in gBRCA metastatic pancreatic cancer after platinum response
Curated highlights from 56 recruiting interventional Lynparza (olaparib) trials in the ClinTrialFinder corpus as of June 23, 2026. Trials are grouped by cancer type and ordered roughly by phase and clinical significance.
Ovarian is where olaparib was born (FDA Dec 2014) and remains the deepest trial pool. Active themes: maintenance-duration optimization, beyond-progression continuation, antibody-drug conjugate combinations.
Olaparib is approved both in metastatic (OlympiAD) and high-risk adjuvant (OlympiA) gBRCA HER2-negative breast. Active trials extend to neoadjuvant TNBC, brain-metastasis radiosurgery combinations, and HR+/HER2- oral-SERD combinations.
PROfound established olaparib in HRR-mutated mCRPC (FDA May 2020); PROpel extended to 1L combination with abiraterone (FDA May 2023). Current trials test platinum/PARPi sequencing, immunotherapy combinations, and radiation/PARPi.
POLO (FDA Dec 2019) was the first targeted maintenance therapy approved in pancreatic cancer (gBRCA after platinum). Current trials expand to PALB2 and to adjuvant settings.
Endometrial is a new PARPi disease, anchored by molecular classification: p53-abnormal (p53abn) endometrial behaves like high-grade serous ovarian and is HRD-enriched.
Beyond the four FDA-approved indications, olaparib is being tested in DDR-mutated and HRD-positive tumors across many other diseases:
Showing curated highlights from 56 recruiting Lynparza (olaparib) interventional trials in the ClinTrialFinder corpus as of June 23, 2026. For the latest list: view all recruiting olaparib trials on ClinicalTrials.gov.
Targets: PARP1 and PARP2 (poly ADP-ribose polymerases) — nuclear enzymes that detect single-strand DNA breaks and recruit the base-excision repair machinery.
Mechanism: Olaparib binds the catalytic site of PARP1/PARP2, blocking enzymatic activity. It also traps PARP-DNA complexes on chromatin (intermediate trapping potency in the class — less than talazoparib, similar to rucaparib). When trapped PARP encounters a replication fork, the resulting collapsed fork generates a double-strand break. Cells with functional homologous recombination (HR) repair these breaks accurately; cells with HR deficiency (BRCA1/2-mutated, HRD-positive) cannot, and die.
Class context: Olaparib was the first PARP inhibitor approved by the FDA (December 2014). Three other PARP inhibitors are now FDA-approved (niraparib/Zejula, rucaparib/Rubraca, talazoparib/Talzenna), each with different potency, trapping ability, and indication footprint. Next-generation PARP1-selective agents like saruparib (AZD5305, AstraZeneca) aim to spare PARP2-mediated hematologic toxicity. See the PARP inhibitor mechanism hub for the cross-drug comparison.
What is Lynparza (olaparib)?
Lynparza is the brand name for olaparib, an oral PARP (poly ADP-ribose polymerase) inhibitor developed by AstraZeneca and co-marketed with Merck. It was the first PARP inhibitor approved by the FDA (December 2014, for BRCA-mutated advanced ovarian cancer) and now has FDA approvals across four cancer types: ovarian, HER2-negative gBRCA breast, HRR-mutated mCRPC, and gBRCA metastatic pancreatic maintenance. Olaparib works by blocking PARP1 and PARP2 enzymes that repair single-strand DNA breaks. In tumors that already have a defect in homologous recombination repair (typically BRCA1 or BRCA2 mutations, or broader HRD), this creates a synthetic-lethal interaction that selectively kills cancer cells while sparing most normal cells.
Which cancers is Lynparza FDA-approved for?
Lynparza has FDA approvals across four cancer types. Ovarian: 1L maintenance in BRCA-mutated advanced ovarian after platinum response (SOLO-1, Dec 2018); 1L maintenance combined with bevacizumab in HRD-positive advanced ovarian (PAOLA-1, May 2020); platinum-sensitive recurrent ovarian maintenance (SOLO-2, Aug 2017). Breast: adjuvant treatment of high-risk HER2-negative germline BRCA-mutated early breast cancer (OlympiA, Mar 2022); HER2-negative gBRCA metastatic breast cancer (OlympiAD, Jan 2018). Prostate: HRR-mutated mCRPC after prior new hormonal therapy (PROfound, May 2020); 1L mCRPC + abiraterone, narrowed to BRCA-mutated after Jun 2023 EMA/NICE refinements (PROpel, May 2023 FDA). Pancreatic: maintenance therapy in gBRCA metastatic pancreatic cancer after platinum (POLO, Dec 2019 — the first targeted maintenance therapy approved in pancreatic cancer).
What does "BRCA-mutated" or "HRD-positive" mean, and how do I get tested?
BRCA1 and BRCA2 are tumor-suppressor genes central to repairing double-strand DNA breaks. Mutations can be inherited (germline) or acquired only in the tumor (somatic) — both types make tumors sensitive to Lynparza. Germline testing uses blood or saliva (often via hereditary cancer panels); somatic testing uses tumor tissue from biopsy. "HRD-positive" (homologous recombination deficiency) is broader: BRCA1/2 mutations plus other HR genes (PALB2, RAD51, BRIP1, BARD1, FANCA) and genomic instability scars. Two FDA-cleared companion diagnostics measure HRD: Myriad MyChoice CDx (used in PAOLA-1 ovarian) and FoundationOne CDx HRD (used in PROfound mCRPC). Talk to your oncologist about which test fits your situation.
What Lynparza trials are currently recruiting?
There are 56 Lynparza (olaparib) interventional trials actively recruiting as of June 2026, spanning all four FDA-approved cancer types plus investigational combinations. Highlights: Phase 3 olaparib + bevacizumab maintenance duration in ovarian (NCT06580314), Phase 3 maintenance olaparib in p53-abnormal endometrial after chemoradiotherapy (NCT06712472 — new disease indication), Phase 3 MITO 35B olaparib beyond progression in ovarian (NCT05255471), Phase 2 olaparib in PALB2 advanced pancreatic (NCT06078787), Phase 2 olaparib + durvalumab in DDR-mutated biliary tract (NCT05222971), Phase 2 olaparib in HRD malignant mesothelioma (NCT04515836), Phase 2 pembrolizumab + olaparib in ES-SCLC (NCT05623319), and Phase 2 olaparib + durvalumab in IDH-mutated solid tumors (NCT03991832). Many combinations test olaparib alongside checkpoint inhibitors (pembrolizumab, durvalumab), tyrosine kinase inhibitors, antibody-drug conjugates (mirvetuximab soravtansine), and oral SERDs (elacestrant).
What are the main side effects of Lynparza?
The most common side effects are anemia (the most common Grade 3+ adverse event, sometimes requiring transfusion), nausea, fatigue, vomiting, neutropenia, and elevated creatinine. A rare but important serious risk is myelodysplastic syndrome / acute myeloid leukemia (MDS/AML), reported in roughly 1–2% of patients with extended exposure; the FDA label includes a warning and routine blood-count monitoring is recommended. Pneumonitis and venous thromboembolism are rare but reported. Lynparza is taken by mouth (300 mg twice daily) and is generally more tolerable than cytotoxic chemotherapy. Combination regimens (with bevacizumab, abiraterone, durvalumab, or chemotherapy) add the toxicities of the partner drug.
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