LYNPARZA® (olaparib): 10 Years Dedicated to Transforming Certain Types of Cancer

Sponsored by AstraZeneca

As the first FDA-approved PARP inhibitor for treatment of certain cancers, LYNPARZA® (olaparib) has been prescribed for approximately 45,500 patients over the last 10 years and provides a targeted therapy option for certain patients who previously had great unmet need.1,2 Read 3 oncologists’ perspectives on the impact of LYNPARZA in personalized oncology medicine.

LYNPARZA® (olaparib) is an innovative, first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response (DDR) in cells/tumors harboring a deficiency in homologous recombination repair (HRR), including those with mutations in BRCA1 or BRCA2 (BRCAm).2-4 Mutations in these genes, resulting in homologous recombination deficiency (HRD), are now known to be associated with an increased risk of developing certain cancers and may confer more aggressive disease.5-7

This mode of action gives LYNPARZA the potential for activity in a range of tumor types with DNA repair deficiencies. While investigation into LYNPARZA’s efficacy in various tumor types is ongoing, LYNPARZA is currently approved across PARP-dependent tumor types with defects and dependencies in the DDR pathway including2:

  • Maintenance treatment of BRCAm advanced or recurrent ovarian cancer and in combination with bevacizumab for maintenance treatment of HRD+ advanced ovarian cancer
  • Treatment of gBRCAm HER2– metastatic and early stage breast cancers
  • Maintenance treatment of gBRCAm metastatic pancreatic cancer
  • Treatment of HRRm metastatic castration-resistant prostate cancer (mCRPC) and treatment of BRCAm mCRPC in combination with abiraterone and prednisone or prednisolone

Please see below for full indications and select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

LYNPARZA is associated with serious and potentially fatal adverse events including myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), pneumonitis, and venous thromboembolism (VTE). Monitor patients for signs and symptoms and discontinue LYNPARZA if MDS/AML or pneumonitis is confirmed. Monitor patients for signs and symptoms of VTE and treat as medically appropriate. LYNPARZA can cause fetal harm.2

Please see below for additional Important Safety Information.

The 2014 FDA approval of LYNPARZA was a significant milestone for patients with advanced ovarian cancer, a patient population in need of more options for maintenance treatment.8,9 Over the last decade, LYNPARZA has become the broadest PARP inhibitor, with 8 indications in different settings across 4 tumor types. It is the only PARP inhibitor with OS data in certain breast, ovarian, and prostate cancers.2,10-13 Once a novel biologic agent at the time of LYNPARZA’s initial approval, PARP inhibitors have become a recommended personalized treatment option in cancers with defects in the DDR pathway.14

The addition of a companion diagnostic to the approval of LYNPARZA helped drive biomarker testing at diagnosis for mutations in genes related to HRR to help inform treatment decisions and identify and select patients for targeted treatment with LYNPARZA.2 Concurrent with the approval of LYNPARZA, the FDA approved the BRACAnalysis CDx® (Myriad Genetics, Inc) for the qualitative detection and classification of variants in the BRCA1 and BRCA2 genes (now approved for ovarian, breast, prostate, and pancreatic cancer indications).15

Since LYNPARZA’s original approval, several other CDx tests have been approved for the identification of mutations in HRR genes, including BRCA1 and BRCA2:15

  • FoundationOne® CDx (Foundation Medicine, Inc) (FDA-approved for ovarian cancer and mCRPC indications)
  • FoundationOne® Liquid CDx (Foundation Medicine, Inc) (FDA-approved for mCRPC indications)
  • MyChoice® CDx (Myriad Genetics, Inc) (FDA-approved for ovarian cancer indications)

LYNPARZA’s Impact in Treating Patients with Ovarian Cancer

Ovarian cancer is one of the most common and is the most fatal gynecologic cancer in the US, with a 5-year relative survival rate of 51%.16 The 5-year survival rate for advanced ovarian cancer is even lower, estimated at around 31%, and over two-thirds of women with ovarian cancer in the US are diagnosed with advanced disease.17 Approximately 20% of women with advanced ovarian cancer in the US have a BRCA mutation, and roughly half have HRD-positive tumors (which includes those with a BRCA mutation).9,18 Given the poor prognosis of patients diagnosed with advanced ovarian cancer, there was a high unmet need for new and improved treatments.9 In clinical trials, LYNPARZA has demonstrated a proven ability to help increase progression-free survival in biomarker-selected patients with advanced ovarian cancer.2

The SOLO-1 trial represents the longest follow-up for any PARP inhibitor in newly diagnosed advanced ovarian cancer.19 In the primary analysis, the primary endpoint, investigator-assessed progression-free survival (PFS), at 3 years was 60% in the olaparib group compared to 27% in the placebo group (HR=0.30, 95% CI: 0.23-0.41, P<0.001).20 In a 5-year post hoc analysis in which median follow-up was 4.8 years in the LYNPARZA group and 5.0 years in the placebo group, LYNPARZA showed a clinically meaningful improvement in median PFS (mPFS), with 56 months (95% CI: 41.9–NR) compared to 13.8 months (95% CI: 11.1-18.2) with placebo (HR=0.33, 95% CI: 0.25-0.43).21 At the 7-year interim overall survival analysis, ~67% of patients were alive with LYNPARZA and ~46.5% were alive with placebo (HR=0.55, 95% CI: 0.40-0.76, P=0.0004); however, the data are not statistically significant at this time point.19

PAOLA-1 is the only PARP inhibitor trial to date that has demonstrated clinically meaningful overall survival (OS) data in the first-line maintenance treatment setting for the HRD-positive subgroup of patients with advanced ovarian cancer. LYNPARZA + bevacizumab reduced the risk of death by 38%, with a median OS of ~6.3 years compared to ~4.8 years with placebo + bevacizumab (HR=0.62, 95% CI: 0.45-0.85).22 OS was a secondary endpoint in a prespecified exploratory subgroup analysis in HRD+ patients.22 With respect to the primary endpoint, investigator-assessed PFS, the primary analysis showed the percentages of patients who were free from disease progression and death in the olaparib-plus-bevacizumab group and the placebo-plus-bevacizumab group were 46% and 28%, respectively, at 24 months (HR=0.59, 95% CI: 0.49–0.72, P<0.001).23

In the post hoc 5-year follow-up analysis in the HRD+ subgroup, LYNPARZA + bevacizumab reduced the risk of disease progression or death by 59% (HR=0.41, 95% CI: 0.32-0.54), with an mPFS of 3.9 years compared to bevacizumab + placebo with ~1.5 years.22 Note that these data were not controlled for Type 1 error and HRD status was not a stratification factor in PAOLA-1. The analysis is based on Kaplan–Meier estimates and is descriptive only. This trial was not designed to assess a statistical difference between treatment groups at 5 years.22

The most common adverse reactions (≥10%) in clinical trials were as follows2:

  • With LYNPARZA as a single agent: nausea, fatigue (including asthenia), anemia, vomiting, diarrhea, decreased appetite, headache, dysgeusia, cough, neutropenia, dyspnea, dizziness, dyspepsia, leukopenia, and thrombocytopenia
  • With LYNPARZA in combination with bevacizumab: nausea, fatigue (including asthenia), anemia, lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and headache

The results from these pivotal studies supported the establishment of LYNPARZA as a standard of care in the first-line maintenance treatment setting for women with advanced ovarian cancer.24

Dr Robert Coleman was contracted with AstraZeneca for this article and received compensation for sharing his perspective. Robert Coleman, MD, FACOG, FACS is a co-director of Gynecologic Oncology Group (GOG) Partners. He has witnessed the impact of PARP inhibitors in gynecological clinical practices and is a passionate advocate for biomarker testing to identify appropriate patients.

Please note that this quote represents Dr Coleman’s personal perspective based on his clinical practice.

“SOLO-1 was a game-changer. It was a bold study, pairing a prognostic and predictive biomarker (germline and tumor BRCA mutation) with a targeted therapy, olaparib, which at the time, had shown great promise as a treatment for patients with recurrent ovarian cancer. The first public disclosure caused many, myself included, to make a double-take at the impact of olaparib on PFS vs placebo. Not only was the prospective value in my patients very real and clinically meaningful (70% reduction in the hazard of progression or death compared to standard of care observation)2 but there was legitimate anticipation of more mature data, including OS data. The follow up PFS data was presented 5 years later, and we thought, "Wow--this is really exciting for patients!"

PAOLA-1 confirmed this finding, using olaparib and bevacizumab maintenance in patients already slated to use bevacizumab maintenance. In a broader defined population (incorporating additional testing to identify BRCA1/2 wild type tumors with genomic instability), the merits of this combination were undeniable and clinical adoption was expedient. Together, these trials induced a magnitude of impact on the natural history of ovarian cancer.

Proving these awesome results will be difficult, but there is an opportunity. Just like the hypothesis tested in SOLO-1, biomarker development – particularly functional, real-time, biologically informative biomarkers – will help to further characterize adaptive changes in the tumor and immune microenvironment, which may be addressed with novel therapeutic strategies. The hope of this iteration will be further customization of care, providing optimal therapeutic intervention to extend the promise first induced by SOLO-1 to more of our patients.

However, none of this can be possible without participation in clinical trials. We owe a huge debt of gratitude to those who have entrusted us with their lives in the pursuit of better care for others through conducting these clinical trials. “Research Cures Cancer” – SOLO-1 and PAOLA-1 are two of many clear examples of work supporting this concept.”

To learn more about LYNPARZA in ovarian cancer, please visit: https://www.lynparzahcp.com/ovarian-cancer/home.html

LYNPARZA’s Impact in Treating Patients with Breast Cancer

Breast cancer is the most common type of cancer among women, with the majority being diagnosed at an early stage.25 For those diagnosed, BRCA mutations are found in approximately 5-10% of patients, some of whom have no family history of the disease.26,27 For those with a BRCA mutation, the risk of recurrent disease continues to be unacceptably high.28

In 2022, LYNPARZA became the first approved PARP inhibitor acting on BRCA mutations in early breast cancer.29 The OlympiA trial showed that identifying a BRCA mutation in women with HER2– high-risk disease opens the additional option of eligibility for LYNPARZA treatment in the adjuvant setting, which helps reduce the risk of recurrence and may improve survival for these breast cancer patients.28,30

In addition to LYNPARZA’s clinical benefits in patients with early breast cancer, the OlympiAD trial demonstrated significant benefits over physician’s choice of chemotherapy in the treatment of patients with gBRCAm HER2-negative metastatic breast cancer.31

The most common adverse reactions (≥10%) in clinical trials were as follows2:

  • With LYNPARZA as a single agent: nausea, fatigue (including asthenia), anemia, vomiting, diarrhea, decreased appetite, headache, dysgeusia, cough, neutropenia, dyspnea, dizziness, dyspepsia, leukopenia, and thrombocytopenia

Dr Lynce was contracted with AstraZeneca for this article and received compensation for sharing her perspective. Filipa Lynce, MD is an Assistant Professor at Harvard Medical School and a Senior Physician at Dana-Farber Cancer Institute. Her clinical expertise is in the treatment of patients with breast cancer and BRCA-associated cancers and her research often focuses on novel therapies in the treatment of breast cancer.

Please note that this quote represents Dr Lynce’s personal perspective based on her clinical practice.

“Olaparib was the first genomically directed therapy approved for the treatment of BRCA-associated breast cancer, initially in the metastatic setting, and now also in the adjuvant setting. It was the first agent of its class to be available for patients with BRCA-associated breast cancer, which brought hope that a more targeted therapy is now available for our patients. While there is still room for improvement both in terms of efficacy and tolerability, olaparib paved the way for the development of PARP1-selective inhibitors and other agents that will continue to focus on taking advantage of specific tumor vulnerabilities that arise in BRCA carriers. Looking forward, I hope to see the development of these agents in combination with antibody drug conjugates, being used earlier in the metastatic setting or as a replacement of chemotherapy for some patients with early stage lower risk tumors.”

To learn more about LYNPARZA in breast cancer, please visit: https://www.lynparzahcp.com/breast-cancer/home.html

LYNPARZA’s Impact in Treating Patients with Prostate Cancer

Prostate cancer is the second most commonly diagnosed cancer in men in the US.32 For men with metastatic castration-resistant prostate cancer (mCRPC), the disease can be quite deadly, especially in those who have failed on a new hormonal anticancer treatment.33 Approximately 20-25% of men with mCRPC have an HRR gene mutation and approximately 10% of patients with mCRPC have BRCA mutations.33 Prior to the approval of LYNPARZA, limited treatment options existed for HRR gene-mutated mCRPC, resulting in a critical need for more targeted therapies that could help delay disease progression in this patient population.33,34

Upon its FDA approval in 2020, LYNPARZA provided a molecularly targeted treatment to men with HRR gene-mutated mCRPC.34 The PROfound trial was the first positive Phase III trial of any PARP inhibitor in mCRPC with results demonstrating a significant reduction in the risk of disease progression or death and improved blinded independent central review (BICR)-assessed rPFS versus investigator’s choice of enzalutamide or abiraterone acetate.2,35

The PROpel trial leading to LYNPARZA’s approval for first-line treatment of BRCAm mCRPC in combination with abiraterone and prednisone or prednisolone was equally important for patients and the oncology community, providing support for a critically needed treatment option in mCRPC.36 PROpel was the first positive phase III trial of a PARP inhibitor in combination with a next-generation hormonal agent (NHA) in a first-line mCRPC population, with the greatest benefit observed in patients with BRCA mutations.36 The results from PROpel illustrate how the combination of LYNPARZA and abiraterone reduces the risk of disease progression or death versus abiraterone alone.36

The most common adverse reactions (≥10%) in clinical trials were as follows2:

  • With LYNPARZA as a single agent: nausea, fatigue (including asthenia), anemia, vomiting, diarrhea, decreased appetite, headache, dysgeusia, cough, neutropenia, dyspnea, dizziness, dyspepsia, leukopenia, and thrombocytopenia
  • With LYNPARZA in combination with abiraterone and prednisone or prednisolone: anemia, fatigue, nausea, diarrhea, decreased appetite, lymphopenia, dizziness, and abdominal pain

The results from both of these pivotal trials underscore the importance of testing for BRCA1/2 and HRR gene mutations at metastatic diagnosis to identify appropriate patients for LYNPARZA, the only PARP inhibitor approved for prostate cancer treatment as both a monotherapy and in combination with abiraterone and prednisone or prednisolone.2

Dr Pedro Barata was contracted with AstraZeneca for this article and received compensation for sharing his perspective. Pedro C. Barata, MD, MSc, FACP is a medical oncologist at University Hospitals Seidman Cancer Center, an Associate Professor of Medicine at Case Western Reserve University School of Medicine, and Director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center. His research interests include experimental therapeutics, the molecular profiling of tumors and genomic-based therapies for genitourinary tumors.

Please note that this quote represents Dr Barata’s personal perspective based on his clinical practice.

"The contribution of olaparib discovery as a targeted therapy revolutionized people's awareness about genetic testing and its importance. Specifically, when looking in the prostate cancer community, we benefit from this therapy either when used alone as a monotherapy or in combination with abiraterone as it compiles the synergistic effect. Both olaparib monotherapy or when being combined with abiraterone have changed patients' lives and offers them an opportunity to live longer."

To learn more about LYNPARZA in prostate cancer, please visit: https://www.lynparzahcp.com/prostate-cancer/home.html

Looking to the Future

AstraZeneca is committed to uncovering additional applications of LYNPARZA to expand usage and help more patients impacted by cancer. LYNPARZA is currently being studied in additional tumor sites and as combination therapy with other agents.

LYNPARZA helps address the unmet needs of many patients with certain types of HRRm/HRD+ cancer based on AstraZeneca’s vision and mission to eliminate cancer as a cause of death by continuing clinical research with the future goal of expanding LYNPARZA’s approved indications. There is always more to be done to deliver the right medicine for the right patient at the right time by performing biomarker testing at diagnosis. Adding LYNPARZA, a first-in-class PARP inhibitor, to the list of approved and available first- and subsequent-line treatments for HRR gene-mutated tumors expands much-needed treatment options for certain high-risk patients earlier.

Important Safety Information

CONTRAINDICATIONS
There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.2% of patients with various BRCAm, gBRCAm, HRR gene-mutated or HRD-positive cancers who received LYNPARZA as a single agent or as part of a combination regimen, consistent with the approved indications, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was approximately 2 years (range: <6 months to >4 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

In SOLO-1, patients with newly diagnosed advanced BRCAm ovarian cancer, the incidence of MDS/AML was 1.9% (5/260) in patients who received LYNPARZA and 0.8% (1/130) in patients who received placebo based on an updated analysis. In PAOLA-1, of patients with newly diagnosed advanced ovarian cancer with HRD-positive status, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA and 2.3% (3/131) in the control arm.

In SOLO-2, patients with BRCAm platinum-sensitive relapsed ovarian cancer, the incidence of MDS/AML was 8% (15/195) in patients who received LYNPARZA and 4% (4/99) in patients who received placebo. The duration of LYNPARZA treatment prior to the diagnosis of MDS/AML ranged from 0.6 years to 4.5 years.

Do not start LYNPARZA until patients have recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor complete blood count for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities, interrupt LYNPARZA and monitor blood count weekly until recovery.

If the levels have not recovered to Grade 1 or less after 4 weeks, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. Discontinue LYNPARZA if MDS/AML is confirmed.

Pneumonitis: Occurred in 0.8% of patients exposed to LYNPARZA monotherapy, and some cases were fatal. If patients present with new or worsening respiratory symptoms such as dyspnea, cough, and fever, or a radiological abnormality occurs, interrupt LYNPARZA treatment and initiate prompt investigation. Discontinue LYNPARZA if pneumonitis is confirmed and treat patient appropriately.

Venous Thromboembolism (VTE): Including severe or fatal pulmonary embolism (PE) occurred in patients treated with LYNPARZA. In the combined data of two randomized, placebo-controlled clinical studies (PROfound and PROpel) in patients with metastatic castration-resistant prostate cancer (N=1180), VTE occurred in 8% of patients who received LYNPARZA, including pulmonary embolism in 6%. In the control arms, VTE occurred in 2.5%, including pulmonary embolism in 1.5%. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism, and treat as medically appropriate, which may include long-term anticoagulation as clinically indicated.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating treatment.

Females
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 months following the last dose.

Males
Advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of LYNPARZA and to not donate sperm during this time.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: nausea (77%), fatigue (67%), abdominal pain (45%), vomiting (40%), anemia (38%), diarrhea (37%), constipation (28%), upper respiratory tract infection/influenza/nasopharyngitis/bronchitis (28%), dysgeusia (26%), decreased appetite (20%), dizziness (20%), neutropenia (17%), dyspepsia (17%), dyspnea (15%), leukopenia (13%), urinary tract infection (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for SOLO-1 were: decrease in hemoglobin (87%), increase in mean corpuscular volume (87%), decrease in leukocytes (70%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), decrease in platelets (35%), and increase in serum creatinine (34%).

ADVERSE REACTIONS—First-Line Maintenance Advanced Ovarian Cancer in Combination with Bevacizumab
Most common adverse reactions (Grades 1-4) in ≥10% of patients treated with LYNPARZA/bevacizumab and at a ≥5% frequency compared to placebo/bevacizumab in the first-line maintenance setting for PAOLA-1 were: nausea (53%), fatigue (including asthenia) (53%), anemia (41%), lymphopenia (24%), vomiting (22%), and leukopenia (18%). In addition, the most common adverse reactions (≥10%) for patients receiving LYNPARZA/bevacizumab irrespective of the frequency compared with the placebo/bevacizumab arm were: diarrhea (18%), neutropenia (18%), urinary tract infection (15%), and headache (14%).

In addition, venous thromboembolism occurred more commonly in patients receiving LYNPARZA/bevacizumab (5%) than in those receiving placebo/bevacizumab (1.9%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients for LYNPARZA in combination with bevacizumab in the first-line maintenance setting for PAOLA-1 were: decrease in hemoglobin (79%), decrease in lymphocytes (63%), increase in serum creatinine (61%), decrease in leukocytes (59%), decrease in absolute neutrophil count (35%), and decrease in platelets (35%).

ADVERSE REACTIONS—Maintenance gBRCAm Recurrent Ovarian Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: nausea (76%), fatigue (including asthenia) (66%), anemia (44%), vomiting (37%), nasopharyngitis/upper respiratory tract infection (URI)/influenza (36%), diarrhea (33%), arthralgia/myalgia (30%), dysgeusia (27%), headache (26%), decreased appetite (22%), and stomatitis (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the maintenance setting for SOLO-2 were: increase in mean corpuscular volume (89%), decrease in hemoglobin (83%), decrease in leukocytes (69%), decrease in lymphocytes (67%), decrease in absolute neutrophil count (51%), increase in serum creatinine (44%), and decrease in platelets (42%).

ADVERSE REACTIONS—Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: nausea (57%), fatigue (including asthenia) (42%), anemia (24%), vomiting (23%), headache (20%), diarrhea (18%), leukopenia (17%), neutropenia (16%), decreased appetite (13%), dysgeusia (12%), dizziness (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the adjuvant setting for OlympiA were: decrease in lymphocytes (77%), increase in mean corpuscular volume (67%), decrease in hemoglobin (65%), decrease in leukocytes (64%), and decrease in absolute neutrophil count (39%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer
Most common adverse reactions (Grades 1-4) in ≥20% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: nausea (58%), anemia (40%), fatigue (including asthenia) (37%), vomiting (30%), neutropenia (27%), respiratory tract infection (27%), leukopenia (25%), diarrhea (21%), and headache (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the metastatic setting for OlympiAD were: decrease in hemoglobin (82%), decrease in lymphocytes (73%), decrease in leukocytes (71%), increase in mean corpuscular volume (71%), decrease in absolute neutrophil count (46%), and decrease in platelets (33%).

ADVERSE REACTIONS—First-Line Maintenance gBRCAm Metastatic Pancreatic Adenocarcinoma

Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: fatigue (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%), and stomatitis (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA in the first-line maintenance setting for POLO were: increase in serum creatinine (99%), decrease in hemoglobin (86%), increase in mean corpuscular volume (71%), decrease in lymphocytes (61%), decrease in platelets (56%), decrease in leukocytes (50%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA for PROfound were: anemia (46%), fatigue (including asthenia) (41%), nausea (41%), decreased appetite (30%), diarrhea (21%), vomiting (18%), thrombocytopenia (12%), cough (11%), and dyspnea (10%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients who received LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

ADVERSE REACTIONS—Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone
Most common adverse reactions (Grades 1-4) in ≥10% of patients who received LYNPARZA/abiraterone with a difference of ≥5% compared to placebo for PROpel were: anemia (48%), fatigue (including asthenia) (38%), nausea (30%), diarrhea (19%), decreased appetite (16%), lymphopenia (14%), dizziness (14%), and abdominal pain (13%).

Most common laboratory abnormalities (Grades 1-4) in ≥20% of patients who received LYNPARZA/abiraterone for PROpel were: decrease in hemoglobin (97%), decrease in lymphocytes (70%), decrease in platelets (23%), and decrease in absolute neutrophil count (23%).

DRUG INTERACTIONS
Anticancer Agents: Clinical studies of LYNPARZA with other myelosuppressive anticancer agents, including DNA-damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity.

CYP3A Inhibitors: Avoid coadministration of strong or moderate CYP3A inhibitors when using LYNPARZA. If a strong or moderate CYP3A inhibitor must be coadministered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid coadministration of strong or moderate CYP3A inducers when using LYNPARZA.

USE IN SPECIFIC POPULATIONS
Lactation: No data are available regarding the presence of olaparib in human milk, its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infant, advise a lactating woman not to breastfeed during treatment with LYNPARZA and for 1 month after receiving the final dose.

Pediatric Use: The safety and efficacy of LYNPARZA have not been established in pediatric patients.

Hepatic Impairment: No adjustment to the starting dose is required in patients with mild or moderate hepatic impairment (Child-Pugh classification A and B). There are no data in patients with severe hepatic impairment (Child-Pugh classification C).

Renal Impairment: No dosage modification is recommended in patients with mild renal impairment (CLcr 51-80 mL/min estimated by Cockcroft-Gault). In patients with moderate renal impairment (CLcr 31-50 mL/min), reduce the dose of LYNPARZA to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

INDICATIONS
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

First-Line Maintenance BRCAm Advanced Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance HRD-Positive Advanced Ovarian Cancer in Combination with Bevacizumab
In combination with bevacizumab for the maintenance 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 deficiency (HRD)-positive status defined by either a deleterious or suspected deleterious BRCA mutation, and/or genomic instability. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance BRCA-mutated Recurrent Ovarian Cancer
For the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated (gBRCAm or sBRCAm) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Adjuvant Treatment of gBRCAm, HER2-Negative, High-Risk Early Breast Cancer
For the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative, high-risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

gBRCAm, HER2-Negative Metastatic Breast Cancer
For the treatment of adult patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

First-Line Maintenance gBRCAm Metastatic Pancreatic Cancer
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. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer
For the treatment of 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. Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

BRCAm Metastatic Castration-Resistant Prostate Cancer in Combination with Abiraterone and Prednisone or Prednisolone
In combination with abiraterone and prednisone or prednisolone (abi/pred) for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Please see complete Prescribing Information, including Medication Guide.

You may report side effects related to AstraZeneca products (Opens new window).

LYNPARZA is a registered trademark of the AstraZeneca group of companies.

©2024 AstraZeneca. All rights reserved. US-89998 Last Updated 6/24

References

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