*As determined by an FDA-approved companion diagnostic for LYNPARZA.

FDA=Food and Drug Administration; gBRCA=germline BRCA; gBRCAm=germline BRCA mutation; mPaC=metastatic pancreatic cancer; PARP=poly (ADP-ribose) polymerase.

In the POLO trial, LYNPARZA nearly doubled median progression-free survival (7.4 months vs 3.8 months with placebo)1

PFS IN FIRST-LINE ACTIVE MAINTENANCE IN PATIENTS WITH gBRCA-MUTATED METASTATIC PANCREATIC CANCER WHO HAD NO EVIDENCE OF DISEASE PROGRESSION AFTER AT LEAST 16 WEEKS OF PLATINUM-BASED CHEMOTHERAPY1,5

In the POLO trial, LYNPARZA nearly doubled median progression-free survival

In POLO, PFS was defined as the time from randomization to disease progression or death from any cause. In the LYNPARZA arm (n=92), there were 55 progression events and 5 death events. Deaths occurred before BICR-documented progression. In the placebo arm (n=62) there were 44 progression events and no deaths.

BID=twice daily; CI=confidence interval; gBRCA=germline BRCA; HR=hazard ratio; PFS=progression-free survival.

Estimated PFS with LYNPARZA vs placebo at 6 months (53% vs 23%); at 1 year (34% vs 15%); and at 2 years (22% vs 10%).5

Percentage of patients who are progression free at 6 months, 1 year, and 2 years are calculated using Kaplan-Meier estimates.

These analyses are descriptive only; the POLO trial was not powered to assess a statistical difference between treatment groups at these timepoints.

POLO: A Phase 3 Trial1,5

  • The POLO trial was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial of LYNPARZA maintenance therapy in patients with gBRCA-mutated metastatic pancreatic cancer
LYNPARZA® (olaparib) Polo Phase 3 Clinical Trial design
LYNPARZA® (olaparib) Polo Phase 3 Clinical Trial design
  • Previous chemotherapy (LYNPARZA n=92, placebo n=62) included FOLFIRINOX variants (79 [86%] vs 50 [81%]); gemcitabine/cisplatin (2 [2%] vs 3 [5%]); other (10 [11%] vs 8 [13%])
  • Best responses observed with first-line chemotherapy (LYNPARZA n=92, placebo n=62) were stable disease (45 [49%] vs 31 [50%]); partial response/complete response (46 [50%] vs 30 [48%])

BICR=blinded independent central review; BID=twice daily; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors.

First-line maintenance therapy for patients with gBRCA-mutated metastatic pancreatic cancer whose disease has not progressed on at least 16 weeks of platinum-based chemotherapy1

In the POLO trial,

LYNPARZA nearly doubled ORR (23% vs 12% with placebo)1

POLO Trial LYNPARZA® (olaparib) ORR 23%
POLO Trial Placebo ORR 12%

Evaluating ORR

  • ORR in patients with measurable disease at baseline (LYNPARZA [n=78]; placebo [n=52])
  • 84% of patients in the POLO study had measurable disease at baseline after receiving platinum-based chemotherapy
  • Almost 1 in 4 patients in the LYNPARZA group with measurable disease after platinum-based chemotherapy achieved a response (vs almost 1 in 8 in the placebo group), including 2 conversions to complete response

In the POLO trial,

Adverse reactions* reported in ≥10% of patients on LYNPARZA1

Adverse Reactions of LYNPARZA® (olaparib) observed in POLO trial
Adverse Reactions of LYNPARZA® (olaparib) observed in POLO trial

*Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.

This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Includes asthenia and fatigue.

§Includes abdominal pain, abdominal pain upper, abdominal pain lower.

||Includes stomatitis and mouth ulceration.

Includes platelet count decreased and thrombocytopenia.

#Includes neutropenia, febrile neutropenia, and neutrophil count decreased.

**Includes rash erythematous, rash macular, and rash maculopapular.

††Includes dyspnea and dyspnea exertional.

AR=adverse reaction.

Lab abnormalities reported in ≥25% of patients on LYNPARZA1

Lab abnormalities of LYNPARZA® (olaparib) reported in POLO trial
Lab abnormalities of LYNPARZA® (olaparib) reported in POLO trial

*This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.

Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.

Represents the proportion of subjects whose mean corpuscular volume was greater than the upper limit of normal (ULN).

In the POLO trial,

More than 9 out of 10 patients were able to continue LYNPARZA treatment without discontinuing due to ARs1

More than 9 out of 10 patients were able to continue LYNPARZA treatment without discontinuing due to ARs
More than 9 out of 10 patients were able to continue LYNPARZA treatment without discontinuing due to ARs

AR=adverse reaction.

Test all patients with pancreatic cancer for germline mutations, including gBRCAm, at diagnosis6

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Pancreatic Adenocarcinoma6

Recommendation for BRCA testing

Germline testing is recommended for any patient with confirmed pancreatic cancer, using comprehensive gene panels for hereditary cancer syndromes.

Recommendation for Pancreatic Adenocarcinoma

Olaparib is included as a Category 2A* recommendation for maintenance therapy for patients with germline BRCA1/2-mutated metastatic adenocarcinoma of the pancreas, with good performance status, and no disease progression following first-line platinum-based chemotherapy.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

*Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Choose LYNPARZA: a new approach to maintain PFS in patients with gBRCA-mutated metastatic pancreatic cancer that has not progressed on at least 16 weeks of first-line platinum-based chemotherapy1-4

As determined by an FDA-approved companion diagnostic for LYNPARZA.

IMPORTANT SAFETY INFORMATION

See Important Safety Information, including Warnings and Precautions for MDS/AML and Pneumonitis, below.

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.

See Important Safety Information, including Warnings and Precautions for MDS/AML and Pneumonitis, below.

INDICATION

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

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.

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%).

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 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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