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Lynparza (olaparib) - 6 indications
Scroll down for information on each indication:
- the treatment of previously treated BRCA mutated advanced ovarian cancer; approved December 2014
- for previously treated patients with deleterious germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer; approved January of 2018
- for the treatment of gBRCAm metastatic pancreatic adenocarcinoma; approved December 2019
- for advanced homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer; approved May 2020
- for patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), HER2-negative high-risk early breast cancer; approved March of 2022
- for patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer; approved May of 2023
General Information
Lynparza (olaparib) is a poly (ADP-ribose) polymerase (PARP) inhibitor.
Lynparza is specifically indicated for the following conditions:
- Ovarian Cancer:
- for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or response to first-line platinum-based chemotherapy
- in combination with bevacizumab for the treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first—line platinum-based chemotherapy and whose cancer is associated with homologous recombination deciency (HRD)-positive status defined by either: a deleterious or suspected deleterious BRCA mutation, and/or genomic instability
- for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum—based chemotherapy
- for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCA m) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy; NO LONGER APPROVED - WITHDRAWN FROM MARKET FOR THIS INDICATION
- for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting
- for the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.
- adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone.
- for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy
- in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer
Lynparza is supplied as a tablet for oral administration. Select patients for treatment with Lynparza based on the presence of deleterious or suspected deleterious HRR gene including BRCA mutations, or genomic instability based on the indication, and sample type. The recommended dosage of Lynparza is 300 mg taken orally twice with or without food. If a patient misses a dose of Lynparza, instruct patient to take their next dose at its scheduled time. Instruct patients to swallow tablets whole. Do not chew, crush, dissolve, or divide tablet.
Scroll down to see the recommended duration of treatment for each condition.
Side Effects
Adverse effects associated with the use of Lynparza may include, but are not limited to, the following:
- nausea
- fatigue
- vomiting
- abdominal pain
- anemia
- diarrhea
- dizziness
- neutropenia
- leukopenia
- nasopharyngitis/upper respiratory tract infection/influenza
- respiratory tract infection
- arthralgia/myalgia
- dysgeusia
- headache
- dyspepsia
- decreased appetite
- constipation
- stomatitis
- dyspnea
- thrombocytopenia
Mechanism of Action
Lynparza is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP1, PARP2, and PARP3. PARP enzymes are involved in normal cellular homeostasis, such as DNA transcription, cell cycle regulation, and DNA repair. Olaparib has been shown to inhibit growth of select tumor cell lines in vitro and decrease tumor growth in mouse xenograft models of human cancer both as monotherapy or following platinum-based chemotherapy. Increased cytotoxicity and anti-tumor activity following treatment with olaparib were noted in cell lines and mouse tumor models with deficiencies in BRCA. In vitro studies have shown that olaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complex, resulting in disruption of cellular homeostasis and cell death.
Indication 1 - previously treated BRCA mutated advanced ovarian cancer
approved December 2014
Treatment Duration
First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer
- Continue treatment until disease progression, unacceptable toxicity, or completion of 2 years of treatment. Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment. Patients with evidence of disease at 2 years, who in the opinion of the treating healthcare provider can derive further benefit from continuous treatment, can be treated beyond 2 years.
First-Line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer in Combination with Bevacizumab
- Continue Lynparza treatment until disease progression, unacceptable toxicity, or completion of 2 years of treatment. Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment. Patients with evidence of disease at 2 years, who in the opinion of the treating healthcare provider can derive further benefit from continuous Lynparza treatment, can be treated beyond 2 years. When used with Lynparza, the recommended dose of bevacizumab is 15 mg/kg every three weeks. Bevacizumab should be given for a total of 15 months including the period given with chemotherapy and given as maintenance
Recurrent Ovarian Cancer, Germline BRCAm Advanced Ovarian Cancer
- Continue treatment until disease progression or unacceptable toxicity
Clinical Trial Results
First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer
The efficacy of Lynparza was evaluated in SOLO-l, a randomized (2: 1), double-blind, placebo-controlled, multi-center trial in 391 patients with BRCA-mutated advanced ovarian, fallopian tube, or primary peritoneal cancer following rst-line platinum-based chemotherapy. Patients were randomized to receive Lynparza tablets 300 mg orally twice daily or placebo. Treatment was continued for up to 2 years or until disease progression or unacceptable toxicity. SOLO-1 demonstrated a statistically significant improvement in investigator-assessed PFS for Lynparza compared to placebo (39% versus 73%, respectively). In addition, 34% of participants experienced ORR for an average of 7.9 months.
First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer in Combination with Bevacizumab
PAOLA—l was a double blind, placebo controlled, multicenter trial that compared the efficacy of Lynparza in combination with bevacizumab versus placebo/bevacizumab for the maintenance treatment of advanced high—grade epithelial ovarian cancer, fallopian tube or primary peritoneal cancer following first-line platinum-based chemotherapy and bevacizumab. Patients were randomized (2:1) to receive Lynparza tablets 300 mg orally twice daily in combination with bevacizumab (n=537) 15 mg/kg every three weeks or placebo/bevacizumab (n=269) Patients continued bevacizumab in the maintenance setting and started treatment with Lynparza after a minimum of 3 weeks and up to a maximum of 9 weeks following 31 completion of their last dose of chemotherapy. Lynparza treatment was continued for up to 2 years or until progression of the underlying disease or unacceptable toxicity. The major efficacy outcome measure was investigator-assessed PFS evaluated according to version 1.1. An additional efficacy endpoint was overall survival (OS). Lynparza added to bevacizumab reduced the risk of disease progression or death by 41% and improved PFS to a median of 22.1 months versus 16.6 months for those treated with bevacizumab alone.
Maintenance Treatment of Recurrent Ovarian Cancer
The efficacy of Lynparza was investigated in two placebo-controlled, multicenter studies in patients with recurrent ovarian cancers who were in response to platinum-based therapy. SOLO-2 The efficacy of Lynparza was evaluated in SOLO-2, a randomized (2:1) double-blind, placebo-controlled trial in patients with gBRCAm ovarian, fallopian tube, or primary peritoneal cancer. Patients were randomized to Lynparza tablets 300 mg orally twice daily or placebo until unacceptable toxicity or progressive disease. The major efficacy outcome measure was investigator-assessed PFS evaluated according to RECIST. SOLO-2 demonstrated a statistically significant improvement in investigator-assessed PFS in patients randomized to Lynparza as compared with placebo (55% versus 81%). Results from a blinded independent review were consistent. The final analysis of OS did not reach statistical significance.
The efficacy of Lynparza was also evaluated in Study 19, a randomized (1:1) double-blind, placebo-controlled trial in 265 patients with platinum-sensitive ovarian cancer who had received 2 or more previous platinum-containing regimens. Patients were randomized to Lynparza capsules 400 mg orally twice daily or placebo until unacceptable toxicity or progressive disease. Study 19 demonstrated a statistically significant improvement in investigator-assessed PFS in patients treated with Lynparza versus placebo (44% versus 73%).
Advanced Germline BRCA-mutated Ovarian Cancer Treated with 3 or More Prior Lines of Chemotherapy; *AstraZeneca voluntarily withdrew this indication from the market in August of 2022*
The efficacy of Lynparza was investigated in a single-arm study of patients with deleterious or suspected deleterious gBRCAm advanced cancers. A total of 137 patients with measurable, advanced gBRCAm ovarian cancer treated with three or more prior lines of chemotherapy were enrolled. All patients received Lynparza capsules 400 mg orally twice daily until disease progression or intolerable toxicity. The efficacy outcome measures were objective response rate and duration of response (DOR) as assessed by the investigator according to RECIST. The ORR was 34% and the DOR was 7.9 months.
This indication was withdrawn based on a subgroup analysis of the Phase III SOLO3 trial. The results showed patients treated with Lynparza saw a 33% greater risk of death than controls who received standard chemotherapy.
Indication 2 - previously treated patients with deleterious germline BRCA-mutated (gBRCAm) HER2-negative metastatic breast cancer
approved January of 2018
Treatment Duration
Continue treatment until disease progression or unacceptable toxicity.
Clinical Trial Results
The efficacy of Lynparza was evaluated in OlympiAD, an open-label randomized (2: 1) study in 302 patients with gBRCAm metastatic breast cancer. Patients were required to have received treatment with an anthracycline (unless contraindicated) and a taxane, in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor-positive disease must have progressed on at least 1 endocrine therapy (adjuvant or metastatic), or have disease that the treating healthcare provider believed to be inappropriate for endocrine therapy. Patients with prior platinum therapy were required to have no evidence of disease progress during platinum treatment. No prior treatment with a PARP inhibitor was permitted. Patients were randomized to Lynparza tablets 300 mg orally twice daily or healthcare provider’s choice of chemotherapy (capecitabine, eribulin, or vinorelbine, at standard doses) until progression or unacceptable toxicity. The major efficacy outcome measure was PFS assessed by blinded independent central review (BICR) using RECIST. A statistically significant improvement in PFS was demonstrated for the Lynparza arm compared to the chemotherapy arm (80% versus 73%).
Indication 3 - the treatment of gBRCAm metastatic pancreatic adenocarcinoma
approved December 2019
Treatment Duration
Continue treatment until disease progression or unacceptable toxicity.
Clinical Trial Results
The FDA approval of Lynparza for pancreatic cancer was based on POLO, a double-blind, placebo-controlled, multi-center trial that randomized (3:2) 154 patients with gBRCAm metastatic pancreatic adenocarcinoma to olaparib 300 mg orally twice daily or placebo until disease progression or unacceptable toxicity. The main efficacy outcome measure was progression-free survival (PFS) by blinded independent central review using RECIST 1.1. Additional efficacy outcome measures were overall survival (OS) and overall response rate (ORR). Median PFS was 7.4 months for patients who received olaparib compared with 3.8 months for patients who received placebo. Median OS for olaparib and placebo was 18.9 months and 18.1 months, respectively; ORR among patients who had measurable disease at baseline was 23% and 12%, respectively.
Indication 4 - advanced homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer
approved May 2020
Treatment Duration
Continue treatment until disease progression or unacceptable toxicity.
Clinical Trial Results
The FDA approval of Lynparza for adult patients with deleterious or suspected deleterious germline or somatic HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone was based on the phase 3 PROFOUND trial. Results from the PROfound trial showed Lynparza reduced the risk of disease progression or death by 66% and improved radiographic progression-free survival (rPFS) to a median of 7.4 months vs. 3.6 months with enzalutamide or abiraterone in men with mCRPC selected for BRCA1/2 or ATM gene mutations, the primary endpoint and a subpopulation of HRR gene mutations. Results also showed Lynparza reduced the risk of radiographic disease progression or death by 51% and improved rPFS to a median of 5.8 months vs. 3.5 months with enzalutamide or abiraterone in the overall trial population of men with HRR gene-mutated mCRPC, a key secondary endpoint. Additional results showed a statistically significant improvement in the key secondary endpoint of overall survival (OS) with Lynparza vs. enzalutamide or abiraterone in men with mCRPC and BRCA1/2 or ATM gene mutations. Results showed Lynparza reduced the risk of death by 31% and improved OS to a median of 19.1 months vs. 14.7 months for those treated with enzalutamide or abiraterone.
Indication 5 - patients with deleterious or suspected deleterious gBRCAm, HER2-negative high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy
approved March of 2022
Clinical Trial Results
This FDA approval was based on results from the Phase 3 OlympiA trial, including data for the trial’s primary endpoint of invasive disease-free survival (IDFS), as well as overall survival (OS) data from a more recent interim analysis. In the OlympiA trial, Lynparza demonstrated a statistically significant improvement in IDFS, reducing the risk of invasive breast cancer recurrences, second cancers or death by 42% versus placebo. Updated results from the OlympiA trial showed Lynparza reduced the risk of death by 32% versus placebo, a statistically significant improvement in OS, a key secondary endpoint.
Indication 6 - deleterious or suspected deleterious BRCAm metastatic castration-resistant prostate cancer
approved May of 2023
Treatment Duration
Continue treatment until disease progression or unacceptable toxicity. When used with Lynparza, the recommended dose of abiraterone is 1000 mg taken orally once daily. Abiraterone should be given in combination with prednisone or prednisolone 5 mg orally twice daily. Refer to the Prescribing Information for abiraterone for dosing information. Patients with mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
Clinical Trial Results
This approval was based on a subgroup analysis of the phase 3 PROpel trial which showed that Lynparza plus abiraterone demonstrated highly clinically meaningful improvements in both radiographic progression-free survival (rPFS) and overall survival (OS) versus abiraterone alone in patients with BRCA mutations. Median rPFS and median OS were not reached for patients treated with Lynparza plus abiraterone versus a median of 8 months and 23 months, respectively, for those treated with abiraterone alone.