EFFICACY

In OlympiAD*

LYNPARZA significantly improved PFS vs HCP’s choice of chemotherapy, with reduction in relative risk of disease progression or death1,2†

Primary endpoint: median progression-free survival1-3


Progression-free survival data Progression-free survival data

Patients who were progression free at 12 months2

  • 25.9% of patients treated with LYNPARZA and 15.0% of patients treated with chemotherapy

Trial was not powered to assess a statistical difference between treatment groups at 12 months.2

*Efficacy was established in OlympiAD, a phase 3, open-label, randomized, controlled, multicenter study of LYNPARZA vs chemotherapy in patients with gBRCAm, HER2-negative mBC treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.1,2
HCP’s chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1,2
Hazard ratio is derived from a stratified log-rank test, stratified by ER, PgR-negative vs ER and/or PgR-positive and prior chemotherapy (yes vs no).1
§For PFS, P-value (2-sided) was compared with 0.05.1

Study Design

In eligible patients with gBRCAm, HER2‐negative mBC, LYNPARZA was studied in a phase 3 trial that included both TNBC and HR-positive breast cancer patients1,2

The OlympiAD trial:

  • A phase 3, open-label, randomized, controlled, multicenter study in which patients (N=302) were randomized 2:1 to receive either LYNPARZA tablets 300 mg BID (n=205) or HCP’s chemotherapy of choice* (n=97)1,2
  • Approximately 29% of patients received LYNPARZA as their first treatment for mBC2
  • Approximately 71% of patients received LYNPARZA as their second or later treatment for mBC2
  • Previous use of chemotherapy for metastatic disease, HR status, and previous use of platinum-based chemotherapy were the primary protocol-specified stratification factors2

*HCP’s chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1,2

LYNPARZA more than doubled ORR (52% vs 23%) vs HCP’s choice of chemotherapy1*

Prespecified secondary endpoint, initial analysis: objective response rate in patients with measurable disease (BICR-assessed)1

Objective response rate data Objective response rate data
  • ORR was a prespecified secondary endpoint. The OlympiAD trial was not powered to assess statistical difference in ORR and median duration of response between treatment groups2
  • The confirmed complete response rate was 7.8% for LYNPARZA and 1.5% for the chemotherapy arm1*
  • The median duration of response was 6.4 months for LYNPARZA and 7.1 months for the chemotherapy arm2*
  • Time of data cutoff for the initial analysis was December 9, 20162

Responses based on confirmed responses.1,2

ORR=CR+PR based on blinded independent central review, according to modified RECIST, version 1.1.1,2

Follow-up analysis: median duration of response reported in patients
who responded (investigator-assessed)4

LYNPARZA median duration of response LYNPARZA median duration of response
  • DoR was exploratory and was not a randomized comparison. Results should be interpreted with caution.
  • Investigator-assessed ORR was recorded in 95 patients (57.6%) in the LYNPARZA arm (n=165) and 16 patients (22.2%) in the chemotherapy arm (n=72)4*
  • Time of data cutoff for the follow-up analysis was September 25, 20174

Median DoR is based on the final analysis using investigator-assessed ORR.4

*HCP’s chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1,4


Final overall survival analysis5

Median overall survival in total study population4

LYNPARZA Overall Survival LYNPARZA Overall Survival
  • OS was a prespecified secondary endpoint. OlympiAD was not powered to show statistical significance in OS for LYNPARZA monotherapy vs chemotherapy.4* OS did not achieve statistical significance4
  • The OlympiAD study protocol was amended in March 2018 to allow exploratory follow-up of patients for survival status and serious adverse events beyond the prespecified final OS survival analysis5
  • At the prespecified OS cutoff (64% maturity), 13% of patients remained on LYNPARZA and no patients remained on chemotherapy4
  • 18 patients (8.8%) remained on LYNPARZA for ≥36 months and no patients remained on chemotherapy5

*HCP’s chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1,2

EXPLORATORY SUBGROUP ANALYSES: Results across subgroups by study stratification factors and results in patients with brain/CNS or visceral metastases

In OlympiAD

Exploratory subgroup analyses: PFS and OS results across patient subgroups defined as study stratification factors

Patients with no prior chemotherapy or prior chemotherapy for mBC1-3
Exploratory subgroup analyses
Exploratory subgroup analyses
Patients with HR-positive mBC or TNBC1-3
Exploratory subgroup analyses
Exploratory subgroup analyses
Patients with no prior platinum-based chemotherapy or prior platinum-based chemotherapy1-3
Exploratory subgroup analyses
Exploratory subgroup analyses
  • OlympiAD was not powered to detect differences in the treatment effect between the arms within these stratification factors; therefore, results from these exploratory analyses should be interpreted with caution because of the modest patient numbers and baseline imbalances1

  • In OlympiAD, previous use of chemotherapy for metastatic disease, HR status, and previous use of platinum-based therapy were the primary protocol-specified stratification factors1,4

  • These subgroups of the full analysis set were analyzed for PFS and OS1,3

  • In this exploratory subgroup analysis, time of data cutoff for median PFS was December 9, 2016, and time of data cutoff for median OS was September 25, 20171,3

*2L+ includes the second line or later lines of treatment.

HCP’s chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1,4

An exploratory analysis of investigator-assessed PFS was consistent with the BICR-assessed PFS results.4

§OS stratification factors were prespecified but not alpha controlled.5,6

In OlympiAD

Exploratory subgroup analyses: ORR results across patient subgroups defined as stratification factors7

Exploratory subgroup analyses
Exploratory subgroup analyses
  • OlympiAD was not powered to detect differences in the treatment effect between these subgroups; therefore, results from these exploratory analyses should be interpreted with caution because of the modest patient numbers and baseline imbalances1

  • In OlympiAD, previous use of chemotherapy for metastatic disease, HR status, and previous use of platinum-based therapy were the primary protocol-specified stratification factors1

  • These subgroups of the full analysis set were analyzed for ORR1

  • Information for these parameters was obtained locally at the time of trial registration with the use of an interactive voice or web-response system1

Response was assessed by BICR in patients with measurable disease.7

*HCP’s chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1,4

2L+ includes the second line or later lines of treatment.

In OlympiAD

Exploratory subgroup analyses: PFS and ORR results in patients with brain/CNS or visceral metastases8

Exploratory subgroup analyses Exploratory subgroup analyses
  • OlympiAD was not powered to detect differences in the treatment effect between these subgroups; therefore, results from these exploratory analyses should be interpreted with caution because of the modest patient numbers and baseline imbalances8

  • Although bone metastasis was reported, no formal analysis was conducted on this subgroup1

*HCP’s chemotherapy of choice (capecitabine, eribulin, or vinorelbine).1,4

An exploratory analysis of investigator-assessed PFS was consistent with the BICR-assessed PFS results.4

References

BICR=blinded independent central review; BID=twice daily; CI=confidence interval; CNS=central nervous system; gBRCAm=germline BRCA-mutated; HER2‐negative=human epidermal growth factor receptor 2-negative; HR=hormone receptor; mBC=metastatic breast cancer; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; TNBC=triple-negative breast cancer.

IMPORTANT SAFETY INFORMATION

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:

Select patients for therapy based on an FDA-approved companion diagnostic for LYNPARZA.

Maintenance Recurrent Ovarian Cancer

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.

Advanced gBRCAm Ovarian Cancer

For the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with 3 or more prior lines of 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.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in <1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The duration of therapy in patients who developed secondary MDS/AML varied from <6 months to >2 years. All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy, and some also had a history of more than one primary malignancy or of bone marrow dysplasia.

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 <1% of patients exposed to LYNPARZA, 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.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, LYNPARZA can cause fetal harm. A pregnancy test is recommended for 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.

Venous Thromboembolic Events: Including pulmonary embolism, occurred in 7% of patients with metastatic castration-resistant prostate cancer who received LYNPARZA plus androgen deprivation therapy (ADT) compared to 3.1% of patients receiving enzalutamide or abiraterone plus ADT in the PROfound study. Patients receiving LYNPARZA and ADT had a 6% incidence of pulmonary embolism compared to 0.8% of patients treated with ADT plus either enzalutamide or abiraterone. 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.

ADVERSE REACTIONS—First-Line Maintenance BRCAm Advanced Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥10% of patients in clinical trials of 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%), UTI (13%), thrombocytopenia (11%), and stomatitis (11%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of 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 compared to a ≥5% frequency for 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 thromboembolic events 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 Recurrent Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of 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%).

Study 19: nausea (71%), fatigue (including asthenia) (63%), vomiting (35%), diarrhea (28%), anemia (23%), respiratory tract infection (22%), constipation (22%), headache (21%), decreased appetite (21%) and dyspepsia (20%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA in the maintenance setting (SOLO-2/Study 19) were: increase in mean corpuscular volume (89%/82%), decrease in hemoglobin (83%/82%), decrease in leukocytes (69%/58%), decrease in lymphocytes (67%/52%), decrease in absolute neutrophil count (51%/47%), increase in serum creatinine (44%/45%), and decrease in platelets (42%/36%).

ADVERSE REACTIONS—Advanced gBRCAm Ovarian Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer after 3 or more lines of chemotherapy (pooled from 6 studies) were: fatigue/asthenia (66%), nausea (64%), vomiting (43%), anemia (34%), diarrhea (31%), nasopharyngitis/upper respiratory tract infection (URI) (26%), dyspepsia (25%), myalgia (22%), decreased appetite (22%), and arthralgia/musculoskeletal pain (21%).

Most common laboratory abnormalities (Grades 1-4) in ≥25% of patients in clinical trials of LYNPARZA for advanced gBRCAm ovarian cancer (pooled from 6 studies) were: decrease in hemoglobin (90%), mean corpuscular volume elevation (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

ADVERSE REACTIONS—gBRCAm, HER2-Negative Metastatic Breast Cancer

Most common adverse reactions (Grades 1-4) in ≥20% of patients in 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 in 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 in clinical trials of 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 in clinical trials of 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 in clinical trials of 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 in clinical trials of LYNPARZA for PROfound were: decrease in hemoglobin (98%), decrease in lymphocytes (62%), decrease in leukocytes (53%), and decrease in absolute neutrophil count (34%).

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).

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