EFFICACY

LYNPARZA: Maintenance treatment for recurrent ovarian cancer—with or without a BRCA mutation1,2

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

SOLO-2

Study 19

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

  gBRCAm=germline BRCA-mutated.

*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 by a central Myriad CLIA test (n=59), subsequently confirmed by BRACAnalysis CDx® (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 relapsed ovarian cancer.

  BRCAm=BRCA mutation; BRCAwt=BRCA wild type; gBRCA=germline BRCA; sBRCA=somatic mutation in BRCA.

*Evaluated according to RECIST, version 1.0.1

As of September 1, 2018, LYNPARZA will be available in the United States in tablet form only. Capsules are not indicated for maintenance treatment.

These studies supported the approval of LYNPARZA tablets in the maintenance setting1

In 2 pivotal trials, LYNPARZA demonstrated PFS in women with and without a BRCAm1-3

SOLO-2: PFS results with LYNPARZA vs placebo1,3

Investigator-assessed PFS

PFS: By BICR

Graph showing LYNPARZA® (olaparib) vs. placebo

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

  • TWO-YEAR FOLLOW-UP: 43% (n=83) of women were progression free on LYNPARZA after 2 years vs 15% (n=13) on placebo3,†

The immature overall survival data showed no difference between the groups.3


ADDITIONAL SENSITIVITY ANALYSIS OF PFS FROM SOLO-2 BY BICR3

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

  • Results from a blinded independent central review (BICR) were consistent with investigator-assessed PFS results, showing a median PFS of 30.2 months in women receiving LYNPARZA and 5.5 months in women receiving placebo

  • Once the treating health care professional determines that the patient has progressed clinically, no further scans are sent for BICR. As a result, the patient is “informatively censored.” Informative censoring may bias the estimate of treatment effect based on BICR

 

Study 19: Significant PFS benefit with LYNPARZA in women with or without a BRCAm1,2
PFS was nearly doubled in a broad population1,2

PFS

Overall survival: >6-year follow-up

Six-year BRCAwt and BRCAm breakdown

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

Graph showing LYNPARZA® (olaparib) vs. placebo with progression-free survival.

PFS in women with BRCAm ovarian cancer was 11.2 months with LYNPARZA vs 4.3 months with placebo4

82% relative risk reduction; HR=0.18; 95% CI: 0.10-0.31; P<0.0001

PFS in women with BRCAwt ovarian cancer was 7.4 months with LYNPARZA vs 5.5 months with placebo4

46% relative risk reduction; HR=0.54; 95% CI: 0.34-0.85; P=0.0075

  • The analysis of the subgroup populations in Study 19 was a preplanned, retrospective analysis. BRCAm status was known for only 98 (37%) of 265 patients at study entry; remaining patients underwent retrospective BRCAm testing4

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

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.1 Although overall survival was a prespecified secondary endpoint, this study was not powered to assess overall survival; this analysis was descriptive6

  • A difference of 2.0 months in overall survival was observed between patients treated with LYNPARZA and those who received placebo, although the criterion for statistical significance (P<0.0095) was not met5,6

  • The HR is unadjusted for crossover5


Study 19: Some women remained on LYNPARZA for more than 6 years—with or without a BRCAm5,6

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

This analysis is descriptive only.

*Most patients in the BRCAm subgroup had gBRCAm, but 20 (15%) of 136 (LYNPARZA group [n=10], placebo group [n=10]) had somatic BRCAm only. Subgroup includes 5 patients without established BRCAm status.6

Percentages derived from overall population assigned to either LYNPARZA (n=136) or placebo (n=128) groups.6

 

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).

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

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