EFFICACY

LYNPARZA: Maintenance indication supported by clinical efficacy data demonstrated in 2 pivotal trials1-3

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

  • 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

Genetic testing is NOT required to determine patient eligibility for maintenance treatment with LYNPARZA1

SOLO-2

Study 19

SOLO-2 study represents patients with relapsed platinum-sensitive ovarian cancer and a BRCAm status.

  gBRCA=germline BRCA.

Evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.1

All patients had a deleterious or suspected deleterious gBRCAm as detected either by a local test (n=236) or central Myriad CLIA test (n=59), subsequently confirmed by BRAC Analysis CDxTM (n=286).1

§ Time to disease progression in the penultimate platinum-based chemotherapy prior to enrollment (6-12 months vs >12 months).1

STUDY-19 represents patients with any BRCA status who have platinum-sensitive ovarian cancer.

  gBRCA=germline BRCA; sBRCA=somatic mutation in BRCA.

*Evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0.1

Capsules are not approved for maintenance treatment.1

These studies supported the approval of LYNPARZA tablets in the maintenance setting.1

LYNPARZA showed significant efficacy as maintenance treatment in 2 studies vs placebo1

SOLO-2 (Phase 3)1,3(tablets)
Patients with a gBRCAm
LYNPARZA (n=196) Placebo (n=99)
Median PFS, months 19.1 5.5
% risk reduction compared with placebo 70% HR=0.30 95% CI: 0.22-0.41; P<0.0001§
Median follow-up, months
PFS follow-up
22.1 22.2
gBRCAm=germline BRCA mutation.

View detailed SOLO-2 data

Study 19 (Phase 2)1,4(capsules)*
All patients, regardless of BRCA status
LYNPARZA (n=136) Placebo (n=129)
Median PFS, months 8.4 4.8
% risk reduction compared with placebo 65% HR=0.35 95% CI: 0.25-0.49; P<0.0001§

View detailed Study 19 data

*Capsules are not indicated for maintenance therapy.1

Hazard ratio from the stratified proportional hazards model, stratified by response to last platinum chemotherapy (complete vs partial) and time to disease progression in the penultimate platinum-based chemotherapy prior to enrollment.1

Hazard ratio is derived from a stratified proportional hazards model, stratified by response to last platinum chemotherapy, time to disease progression in the penultimate platinum-based chemotherapy, and Jewish and non-Jewish descent.1

§ The P value is derived from a stratified log-rank test.1

In SOLO-2, LYNPARZA significantly improved PFS in patients with a BRCAm by more than 1 year vs placebo1

INVESTIGATOR-ASSESSED RESULTS FROM SOLO-2 (patients with a gBRCAm)1,3

Graph showing how LYNPARZA® (olaparib) reduces risk of disease progression or death vs. placebo.

  • According to the Kaplan-Meier survival estimator, 24-month PFS was 43% (35.5-50.4) for patients on LYNPARZA vs 15% (8.6-23.2) on placebo3

ADDITIONAL SENSITIVITY ANALYSIS OF PFS Results from a blinded independent review were consistent.1

In Study 19, LYNPARZA nearly doubled PFS in a broad platinum-sensitive patient population—regardless of BRCA status1,4

PFS

Overall survival

RESULTS FROM STUDY 19 (patients with platinum-sensitive disease)1

Graph showing how LYNPARZA® (olaparib) improves disease control vs. placebo with extended progression-free survival.

*LYNPARZA capsules are not indicated for maintenance treatment.1

Final overall survival analysis after more than 5 years’ total follow-up4

  • Median overall survival was 29.8 months with LYNPARZA vs 27.8 months with placebo (HR=0.73; 95% CI: 0.55-0.95)1,†

Without adjusting for multiple analyses. Not statistically significant.1

LONG-TERM FOLLOW-UP4 13% of all study patients (n=18) remained on LYNPARZA treatment and 1% (n=1) remained on placebo for 5 years or more. On LYNPARZA treatment: Approximately 60% (n=11) had a BRCAm Approximately 40% (n=7) were BRCA wild type On placebo: One patient had a BRCAm

Percentages derived from overall population assigned to either LYNPARZA (n=136) or placebo (n=129) groups.

 

INDICATIONS

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

  • 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 (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

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.

ADVERSE REACTIONS—Maintenance Setting

Most common adverse reactions (Grades 1-4) in ≥20% of patients in clinical trials of LYNPARZA in the maintenance setting for SOLO-2: 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%), and decreased appetite (21%).

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 (including 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%), increase in mean corpuscular volume (57%), decrease in lymphocytes (56%), increase in serum creatinine (30%), decrease in platelets (30%), and decrease in absolute neutrophil count (25%).

DRUG INTERACTIONS

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

CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If a strong or moderate CYP3A inhibitor must be co-administered, reduce the dose of LYNPARZA. Advise patients to avoid grapefruit, grapefruit juice, Seville oranges, and Seville orange juice during LYNPARZA treatment.

CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers when using LYNPARZA. If a moderate inducer cannot be avoided, there is a potential for decreased efficacy of 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 hepatic impairment (Child-Pugh classification A). There are no data in patients with moderate or severe hepatic impairment.

Renal Impairment: No adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min). In patients with moderate renal impairment (CLcr=31-50 mL/min), reduce the dose to 200 mg twice daily. There are no data in patients with severe renal impairment or end-stage renal disease (CLcr ≤30 mL/min).

DOSING AND ADMINISTRATION

To avoid substitution errors and overdose, do not substitute LYNPARZA tablets with LYNPARZA capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Recommended tablet dose is 300 mg, taken orally twice daily, with or without food. Continue treatment until disease progression or unacceptable toxicity. For adverse reactions, consider dose interruption or dose reduction.

Please see complete Prescribing Information, including Patient Information (Medication Guide).

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-10881-800-FDA-1088.