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                Resources for Information | Approved Drugs

Resources for Information | Approved Drugs

                        Oncology (Cancer) / Hematologic Malignancies Approval Notifications
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          FDA D.I.S.C.O.: Olaparib for gBRCAm HER2-negative metastatic breast cancerResources for Information | Approved Drugs FDA D.I.S.C.O.: Olaparib for gBRCAm HER2-negative metastatic breast cancer
  
  	
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*FDA medical oncologists discuss the January 12, 2018, approval of olaparib, the first PARP inhibitor approved for the treatment of patients with metastatic breast cancer with a germline BRCA mutation.*

Sanjeeve Bala: Welcome back to the DISCO, the FDA’s Soundcast in Clinical Oncology from the Oncology Center of Excellence. We are in Silver Spring, MD, and during our soundcasts, we discuss recent FDA approvals of cancer drugs and therapies. We hope this information will help you to better understand these approvals and how new drugs and therapies are benefitting cancer patients. Today we’ll be discussing the recent approval of olaparib for the treatment of select patients with breast cancer.

I’m Dr. Sanjeeve Bala, a medical oncologist and clinical team leader at FDA, and I am joined by my colleague Dr. Abhi Nair, also a medical oncologist at the Oncology Center of Excellence here at the FDA.

Abi Nair: Hi everyone. Thanks for joining us. Olaparib, which is marketed as Lynparza, was approved for the treatment of patients with HER2 negative metastatic breast cancers that harbor germline BRCA-mutations, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

SB: The recommended dose of olaparib is 300 mg taken orally twice daily with or without food. Of note, this approval is for the tablet formulation of olaparib.The FDA approval of this treatment is focused on patients with other specific breast cancer characteristics. These include: Patients with hormone receptor-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Patients should be selected for treatment with olaparib based on the results of an FDA-approved companion diagnostic test for the presence of a deleterious germline BRCA mutation. The approval also includes men with metastatic HER-2 negative, germline BRCA mutated breast cancer. Abhi, can you tell us about the treatment setting for which olaparib received this approval?

AN: Sure, Sanjeeve. Broadly speaking, for patients with HER-2 negative metastatic breast cancers expressing hormone receptors, systemic treatment begins with endocrine therapy such as tamoxifen, until hormones are no longer effective. These patients would then be treated with sequential single-agent chemotherapy regimens, similar to the treatment paradigm for patients whose tumors do not express hormone receptor.

SB: Thanks, Abhi. So, the approval of olaparib for these patients represents the first PARP inhibitor approved for the treatment of patients with metastatic breast cancer with a germline BRCA mutation. Three PARP inhibitors already have approval for use in various settings for women with ovarian cancer, as we’ve discussed at the DISCO previously. Why don’t you give us a brief reminder about the drug olaparib.

AN: Sure, Sanjeeve. Olaparib, as you mentioned, is a PARP inhibitor. This class of drugs inhibits a specific DNA repair pathway. Cancer cells can be deficient in homologous recombination repair mechanisms, which can be caused by BRCA mutations as well as potentially several other deleterious genetic changes. These cells can’t recover from the DNA damage that accumulates when inhibiting the enzyme PARP with a drug like olaparib, resulting in the death of those cancer cells. Sanjeeve, why don’t you go ahead and tell us about the trial design.

SB: This approval was based on a study called OlympiAD, which was an open-label, multi-center trial that randomized 302 patients 2 to 1 who had germline BRCA mutation and HER2-negative metastatic breast cancer to olaparib tablets, 300 mg orally twice daily, or to their physician’s choice of chemotherapy. These chemotherapy options included capecitabine, vinorelbine, or eribulin, which are standard chemotherapy options in this setting. All patients must have had prior chemotherapy, as adjuvant, neoadjuvant, or for metastatic disease. Patients were stratified by prior chemotherapy use in the metastatic setting, hormone receptor-positive vs. triple-negative, and prior use of platinum-based chemotherapy.

AN: This sounds like a standard randomized trial design, and the stratification factors sound reasonable. What was the efficacy outcome?

SB: Right. The primary efficacy outcome was progression-free survival (PFS) as assessed by blinded independent central review, with a median PFS of 7.0 months in the olaparib arm, and 4.2 months in the chemotherapy arm, resulting in a hazard ratio of 0.58.

AN: OK, that’s a meaningful clinical benefit. How about the toxicity of the treatment?

SB: Oncologists should be pretty familiar with the PARP inhibitors these days, and this study didn’t uncover any surprising safety signals. The most common toxicities are anemia and other cytopenias, as well as nausea, fatigue, and vomiting. Important but rare toxicities of olaparib include pneumonitis and AML/MDS. The approved prescribing information has additional data about the safety of this treatment.

AN: So, since this drug is indicated for patients with a molecular biomarker, tell us how these patients are selected for treatment with olaparib.

SB: Sure, Abhi. Concurrent with the approval and based on testing of patients on the OlympiAD trial, FDA granted marketing authorization for the BRACAnalysis CDx test as a companion diagnostic device to identify patients with deleterious or suspected deleterious germline BRCA mutation who may be eligible for treatment with olaparib.

AN: Thanks, Sanjeeve. Give us the three take-aways for this DISCO.

SB: OK. 1) olaparib is the first PARP inhibitor approved for the treatment of patients with germline BRCA-mutated metastatic breast cancer; 2) patients should be selected using an FDA-approved BRCA test; and 3) no new safety signals were identified, with anemia, nausea, and fatigue occurring most commonly.

SB: You can find more detailed prescribing and safety information in the approved prescribing information, also available on the web at drugs@fda.

For a transcript with links to an in-depth look at the FDA analysis, and the multidisciplinary team of FDA experts who conducted the review, visit the FDA Oncology Center of Excellence DISCO website at fda.gov/DISCO.

AN: Thank you Sanjeeve. Are there other FDA oncology drug approvals that you would like to hear about? Leave us your questions and comments on Twitter @FDAOncology or send us an email to: FDAOncology@fda.hhs.gov. I’m Abhi Nair, thank you for tuning in to DISCO today.

S: And until next time at the DISCO, I’m Sanjeeve Bala.

                                                                                  Content current as of:
      10/23/2018
              
              
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						  OncologyResources for Information | Approved Drugs

          
                        Oncology (Cancer) / Hematologic Malignancies Approval Notifications
          Ongoing | Cancer Accelerated Approvals
          Verified Clinical Benefit | Cancer Accelerated Approvals
          Withdrawn | Cancer Accelerated Approvals
          Other | Cancer Accelerated Approvals


                        Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) Short Description
 
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