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Fellow ION Member,

Please see below information on Lynparza® (olaprarib), the only PARPi FDA-approved in first-line maintenance for patients with both somatic BRCA and germline BRCA-mutated advanced ovarian cancer. Data from SOLO-1, a phase III, double-blind, randomized, controlled multicenter trial of Lynparza, which was conducted in 391 patients with BRCAm advanced ovarian, fallopian tube, or primary peritoneal cancer following complete or partial response to their first line of platinum-based chemotherapy, led to this FDA approval.

Important safety information is included below.

Regards,
Ralph Boccia, MD, FACP
Chair, ION Medical Advisory Panel
 
  View complete Prescribing Information and Important Safety Information.  
 
 
 
Dear Amy,
 
Based on new clinical data, you can now prescribe LYNPARZA, an oral therapy, for first-line maintenance treatment of adult patients with deleterious or suspected deleterious BRCAm advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.1,*
*Select patients with gBRCAm advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer for therapy based on an FDA-approved companion diagnostic for LYNPARZA.1

The Landmark SOLO-1 Trial

Trial Design
A phase III, double-blind, randomized, controlled, multicenter trial of LYNPARZA conducted in 391 patients with BRCAm advanced ovarian, fallopian tube, or primary peritoneal cancer following complete or partial response to their first line of platinum-based chemotherapy.1,4
Patients were randomly assigned 2:1 to LYNPARZA (two 150 mg tablets twice daily; 600 mg per day) or placebo1,4
Treatment continued for up to 2 years or until disease progression1,4
For patients who remained in complete clinical response (no radiological evidence of disease), maximum duration of treatment was 2 years1,4
Patients with evidence of disease at 2 years, who in the opinion of the treating physician can derive further benefit from continuous treatment, can be treated beyond 2 years1
 

SELECT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

LYNPARZA is associated with serious, potentially fatal risks, including MDS/AML, Pneumonitis, and Embryo-Fetal Toxicity. Please see Important Safety Information below for more details.
LYNPARZA Delivered Significantly Sustained Efficacy1,4
 

SELECT SAFETY INFORMATION

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%).
BRCAm=BRCA-mutated; PARPi=poly (ADP-ribose) polymerase inhibitor; PFS=progression-free survival.
LYNPARZA IS APPROVED FOR BOTH SOMATIC AND GERMLINE BRCAm ADVANCED OVARIAN CANCER1
Select patients with gBRCAm advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer for therapy based on an FDA-approved companion diagnostic for LYNPARZA1
An FDA-approved test for the detection of tumor BRCA gene mutation for the first-line maintenance treatment of advanced ovarian cancer is not currently available1
AT DIAGNOSIS, PARTNER WITH YOUR HEALTH CARE TEAM TO FACILITATE BRCA TESTING
In women with ovarian cancer:
- ~15% have a germline BRCAm5
- ~7% have a somatic BRCAm6
Germline BRCA mutations are present in blood and tumors7
Somatic BRCA mutations are present only in tumors7
For more information on using LYNPARZA for first-line maintenance in women with BRCAm advanced ovarian cancer, please read1:
 
 
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—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%).
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 adjustment to the starting dose is necessary in patients with mild renal impairment (CLcr=51-80 mL/min) but patients should be monitored closely for toxicity. 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).
INDICATION
LYNPARZA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:
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 with gBRCAm advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer for therapy based on an FDA-approved companion diagnostic for LYNPARZA.
Please see complete Prescribing Information, including Patient Information (Medication Guide).
You may report side effects related to AstraZeneca products by clicking here.
References: 1. LYNPARZA® (olaparib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018. 2. Zejula [full Prescribing Information]. Waltham, MA: TESARO, Inc; 2018.
3. Rubraca [full Prescribing Information]. Boulder, CO: Clovis Oncology, Inc; 2018. 4. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer [published online October 21, 2018]. N Engl J Med. doi:10.1056/NEJMoa1810858. 5. Pal T, Permuth-Wey J, Betts JA,
et al. BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases. Cancer. 2005;104(12):2807-2816. 6. Pennington KP, Walsh T, Harrell MI, et al. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clin Cancer Res. 2014;20(3):764-775. 7. Frey MK, Pothuri B. Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature. Gynecol Oncol Res Pract. 2017;4:4.
This product information is intended for US health care professionals only.
LYNPARZA is a registered trademark of the AstraZeneca group of companies.
©2019 AstraZeneca. All rights reserved. US-25742 Last Updated 1/19
 

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