New FDA Approval for LYNPARZA® (olaparib)

LYNPARZA® (olaparib)

March, 2022

I am excited to announce that the US Food and Drug Administration (FDA) has approved a new indication for LYNPARZA® (olaparib) 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.

LYNPARZA is the first and only targeted adjuvant therapy with an FDA-approved indication specifically for patients with gBRCAm,* HER2-negative, high-risk† early breast cancer for patients who have been treated with neoadjuvant or adjuvant chemotherapy.

FDA approval was based on the results from the OlympiA phase 3 trial, which was presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. Please see the attached documents for more information regarding the use of LYNPARZA in this new indication:

LYNPARZA® (olaparib) EMR Treatment Plan

This document is a customizable draft treatment plan for implementation into EMR or papertreatment plans. The information contained in the attachment is derived from the full Prescribing Information for LYNPARZA

LYNPARZA® (olaparib) Medical Policy Considerations

Intended to provide example coveragepolicy language for LYNPARZA, it is not meant to provide clinical advice concerning any pharmaceutical products or medical procedures

LYNPARZA® (olaparib) Sell Sheet: Contains information regarding the study design, efficacy, andsafety data from the OlympiA phase 3 trial

This is the eighth indication approved for LYNPARZA in the US. See Important Safety Information below.

For more information regarding the approval, please see AstraZeneca’s press release announcing the news.

Please feel free to reach out with any questions or to request a presentation.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

There are no contraindications for LYNPARZA.

WARNINGS AND PRECAUTIONS

Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in approximately 1.5% of patients exposed to LYNPARZA monotherapy, and the majority of events had a fatal outcome. The median duration of therapy in patients who developed MDS/AML was 2 years (range: <6 months to >10 years). All of these patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

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.

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—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%).

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).

INDICATION

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

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.

Please see complete Prescribing Information, including Medication Guide.

You may report side effects related to AstraZeneca products by clicking here. If you prefer to report these to the FDA, either visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

Regards,

Amy Kelly

National Oncology Account Director

US Oncology Access Strategy

West Region

AstraZeneca Pharmaceuticals

One Medimmune Way, Gaithersburg, MD, 20878

Mobile: 612-810-4591

Email: Amy.Kelly@astrazeneca.com

gBRCAm=germline breast cancer susceptibility gene-mutated; PARPi=poly (ADP-ribose) polymerase inhibitor; pCR=pathologic complete response.

*Select patients for this indication based on an FDA-approved companion diagnostic.

†For patients who received prior neoadjuvant chemotherapy, high-risk was defined as non-pCR in TNBC and as

non-pCR with CPS&EG score ≥3 in HR-positive, HER2-negative disease. For patients who received prior adjuvant chemotherapy, high-risk was defined as ≥pN1 or ≥pN0 with ≥pT2 in TNBC and as ≥4 positive lymph nodes in HR-positive, HER2-negative disease.

For more information, please visit www.lynparzahcp.com.

Reference: LYNPARZA® (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022.

This product information is intended for US health care professionals only.

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

New FDA Approval for LYNPARZA® (olaparib)