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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.: Rucaparib in Ovarian CancerResources for Information | Approved Drugs FDA D.I.S.C.O.: Rucaparib in Ovarian Cancer
  
  	
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*FDA medical oncologists discuss the agency’s December 2016 accelerated approval of rucaparib for treatment of patients with deleterious BRCA mutation associated advanced ovarian cancer who have been treated with two or more chemotherapies.*

*Transcript:*

Sanjeeve Bala: Welcome to the D.I.S.C.O. Today’s Drug Information Soundcast in Clinical Oncology from FDA’s Oncology Center of Excellence will focus on the recent approval of rucaparib, marketed as RUBRACA.

Abhi Nair: Precision medicine has invaded the field of oncology like no other medical specialty. Recently, most FDA oncology approvals have been in biomarker-selected subpopulations of common cancers. With the approval of rucaparib, the field of ovarian cancer saw another such approval.

AN: Hi, I’m Abhi Nair, a medical officer at the Oncology Center of Excellence here at the FDA.

SB: And I am Sanjeeve Bala, one of the medical officers who reviewed this application.

AN: So, Sanjeeve, first, let’s start with the basics. Tell me about rucaparib.

SB: Rucaparib is a PARP inhibitor. PARP inhibitors have been in clinical trials for several years. The indication for rucaparib is for patients who have been treated with two or more prior chemotherapy regimens. In 2014, olaparib was the first approval in this class, for a later line of therapy. A few other agents are in development.

AN: So these PARP inhibitors aren’t for all women with ovarian cancer. Tell me more about the patients we can use rucaparib for.

SB: Rucaparib is approved for use in patients with advanced ovarian cancer and who have been treated with two or more chemotherapies, and whose tumors have deleterious changes in *BRCA1* or *BRCA2*. Until now, *BRCA* mutation was evaluated on blood specimens, which would reveal only germline mutations. This approval is for *BRCA* changes found in tumor tissue, which may be either germ line or somatic mutations, as detected by the FDA-approved test FoundationFocus CDxBRCA. So through this test, more patients may be identified for treatment with rucaparib.

AN: What was the basis for the approval of rucaparib in this patient population?

SB: The efficacy of rucaparib was studied in two single-arm clinical trials; 106 patients were identified to have *BRCA*-mutated advanced ovarian cancer using a next-generation sequencing testing platform. They were treated with rucaparib 600 mg orally twice daily. The investigator-assessed objective response rate was 54%. The median duration of response for the 57 responders was 9.2 months. This surrogate measure of efficacy led to the accelerated approval of rucaparib for this indication.

AN: So, Sanjeeve, if I understood that, by accelerated approval, you mean that the surrogate endpoint of response rate was used to approve the drug. This made it available to patients earlier than if using an endpoint such as overall survival, correct?

SB: Yes, but because this approval relied on a surrogate endpoint, confirmatory trials, which are ongoing, must support these conclusions.

AN: What were some of the regulatory considerations that the team reviewed in this application?

SB: The data submitted included overall response rate per RECIST criteria as assessed by the investigator. However, an independent radiology review committee provided data that were supportive.

AN: OK, great! Sounds like this application also had some other important regulatory aspects. Can you elaborate on these?

SB: The FDA reviewed the application as a priority review. This means that we devoted more resources to review it, approving it two months ahead of schedule. Rucaparib was approved along with the companion diagnostic, the FoundationFocus CDxBRCA test. This test is the first next generation sequencing-based test that the FDA has approved.

AN: Hmm, that sounds interesting. Tell us more about the companion diagnostic approval.

SB: This assay is performed on tumor tissue, as opposed to a blood test or a cheek swab. As a result, clinicians can get information about the tumor’s susceptibility to PARP inhibition even if the patient does not have a familial, or germline, *BRCA* mutation.

AN: So were there any subpopulations of interest with any major differences in efficacy and safety?

SB: As expected for patients with ovarian cancer, the response rate appears to be different if patients meet the standard definitions of platinum sensitivity, with lower response rates in patients considered platinum resistant or platinum refractory. On the other hand, it did not seem to matter whether the mutation was in the *BRCA1*or *2* gene—the benefits were the same.

AN: When I start a patient on rucaparib, what are some of the safety risks that I should be aware of?

SB: Most of the adverse events, as expected for the PARP inhibitor class, were related to the GI tract, such as nausea, vomiting, and abdominal pain, and hematologic toxicities such as anemia and thrombocytopenia. Fatigue was the most frequent adverse event that led to patients discontinuing the drug. We saw a very low rate of myelodysplastic syndrome or acute myelogenous leukemia, reported in 0.5% of patients. So it’s important to do routine blood counts to monitor for such events.

AN: So to conclude, Sanjeeve, where do you see rucaparib fitting in the treatment of advanced ovarian cancer patients?

SB: For selected women with *BRCA*-mutated tumors, PARP inhibition can be a useful treatment option to delay re-exposure to platinum-based regimens, if they’ve progressed after two such regimens. Refer to the package insert for more details. An in-depth look at the FDA review is available at the FDA Oncology Center of Excellence website.

AN: Are there other FDA hematology or oncology drug approvals that you would like to hear about? Please tweet us your questions and comments, and follow us on Twitter @FDAOncology. I’m Abhi Nair and thank you for listening.

SB: And until our next Oncology Center of Excellence soundcast, I’m Sanjeeve Bala.

*Acknowledgements*

*This Drug Information Soundcast in Clinical Oncology was developed by Sanjeeve Bala, Abhilasha Nair, Kirsten B. Goldberg, and Richard Pazdur, of the Oncology Center of Excellence and the Office of Hematology and Oncology Products. Steven Jackson of the Division of Drug Information was the sound producer.*

*The**FDA review documents**for this product approval are available on Drugs@FDA.*

*Members of the Multi-Disciplinary Review and Evaluation team for this product application were:*

**Regulatory Project Manager**
			Kim Robertson**Nonclinical Reviewer**
			Haw-Jyh (Brian) Chiu**Nonclinical Team Leader**
			Todd Palmby**Office of Clinical Pharmacology Reviewer(s)**
			Sarah Schrieber / Jinzhong Liu**Office of Clinical Pharmacology Team Leader(s)**
			Pengfei Song**Associate Director for Labeling**
			William Pierce**Clinical Reviewer for Efficacy**
			Sanjeeve Balasubramaniam**Clinical Reviewer for Safety**
			Sara Horton**Clinical Team Leader**
			Julia Beaver**Statistical Reviewer**
			Laura Fernandes**Statistical Team Leader**
			Shenghui Tang**Cross-Disciplinary Team Leader**
			Julia Beaver**Division Director (DHOT)**
			John Leighton**Division Director (OCP)**
			Nam Atiqur Rahman**Division Director (OB)**
			Rajeshwari Sridhara**Division Director (OHOP)**
			Geoffrey Kim**Office Director (or designated signatory authority)**
			Richard Pazdur

*Additional reviewers were:*

**OPQ**
			Kristine Leahy**Microbiology**
			Xing Wang**OPDP**
			Nicholas Senior**OSI**
			Lauren Iacono-Connor**OSE/DEPI**
			Carolyn McCloskey / Steven Bird**OSE/DMEPA**
			Tingting Gao**OSE/DRISK**
			Mei-Yean Chen

                                                                                  Content current as of:
      05/17/2017
              
              
Regulated Product(s)
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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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