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                        Oncology (Cancer) / Hematologic Malignancies Approval Notifications
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          FDA D.I.S.C.O.: Niraparib in Ovarian Cancer TranscriptResources for Information | Approved Drugs FDA D.I.S.C.O.: Niraparib in Ovarian Cancer Transcript
  
  	
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*FDA medical oncologists discuss the agency’s March 2017 approval of niraparib for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.*

Transcript:

Sanjeeve Bala: Welcome to the DISCO.

Abhi Nair: This is Abhi Nair, medical officer at the Oncology Center of Excellence.

SB: And I’m Sanjeeve Bala, acting clinical team leader in the OCE. Today’s Drug Information Soundcast in Clinical Oncology from FDA’s Oncology Center of Excellence covers the recent approval of niraparib, marketed as Zejula, for the treatment of women with ovarian cancer. This new PARP inhibitor is approved in the maintenance setting for all women with ovarian cancer following a response to their platinum-based treatment for recurrent disease. This represents a major shift in the usage of PARP inhibitors in this disease setting.

AN: So, Sanjeeve, we’re back to discussing another recent approval for women with ovarian cancer, with another PARP inhibitor, niraparib. This makes the third approval in ovarian cancer in the past 6 months. Sanjeeve, can you tell us about the indication for this approval? SB: Sure. The indication for niraparib is unique, and a key feature of this approval. Niraparib is approved for the maintenance treatment of adult patients with recurrent ovarian cancer following a complete or partial response to platinum-based chemotherapy.

AN: Hmm, approval in the maintenance setting. That definitely sounds new. Can you tell us more?

SB: Yeah, this is the first PARP inhibitor approved for the maintenance treatment of patients who have had a measureable response to their platinum-based treatment for relapsed ovarian cancer. So patients can start this treatment after the completion of their second regimen of chemotherapy if their tumors shrank. It can then be continued until disease progression. But Abhi, there’s another feature of the indication that’s unique. Did you pick up on that?

AN: Well, I did notice that PARP inhibitors have been studied so far for treatment of ovarian cancers associated with *BRCA* mutations, but I didn’t hear you mention that in the indication.

SB: That’s right. In the randomized, placebo-controlled NOVA trial, women with recurrent ovarian cancer who had responses to standard platinum-based chemotherapy were stratified based on the FDA-approved BRCAnalysis assay into cohorts with germline BRCA mutation or wildtype BRCA. Women in the treatment arm took niraparib 300 mg orally daily. Imaging was interpreted by independent radiologic review with additional clinical review. In the primary analysis, progression-free survival was improved in the women with germline BRCA mutation as well as the women with wildtype *BRCA*.

AN: But, Sanjeeve, as we discussed for the rucaparib approval, aren’t there somatic mutations and other molecular changes that could be confounding this finding in the wildtype cohort?

SB: That possibility was investigated by testing for genetic markers of homologous recombination deficiency, including tumor *BRCA* mutation, in this cohort. In all planned and exploratory subgroups, including those with wildtype tumors, we saw a PFS advantage for those women who were taking niraparib. As a result, the BRCAnalysis test is labeled as a complementary diagnostic.

AN: Explain how a complementary diagnostic is different from a companion diagnostic? In the rucaparib podcast, I remember we talked about the companion diagnostic that was required for selecting patients for treatment with rucaparib.

SB: You know, that’s a common question. Basically, a companion diagnostic device is essential for the safe and effective use of the drug, and is identified in the product label. In this case, niraparib does not require testing with a companion diagnostic, since it was found that patients negative for the marker could also potentially benefit. In contrast, we have situations where a drug may have a favorable clinical benefit in the entire population of patients, but a subset of those patients identified by a test have a greater benefit. That test would be a complementary diagnostic. It is not required for the use of the drug, but provides information about a population who may derive greater benefit. It can help inform the discussion between prescriber and patient. In this case, women with *BRCA* mutated ovarian cancer have the greatest benefit from treatment with niraparib, and so the complementary diagnostic can inform the risk-benefit analysis for its use, but it is not required.

AN: So the complementary diagnostic is not required for the use of niraparib.

SB: That’s correct.

AN: Sounds like this clinical trial was really well designed. So what kind of clinical benefit did the treatment provide?

SB: For women with germline *BRCA* mutation, median PFS increased from 5.5 months to 21 months. In the cohort without germline *BRCA* mutation, median PFS increased from 3.9 months to 9.3 months.

AN: Great. And were the adverse events similar to others in the PARP inhibitor class?

SB: Yes and no. The usual PARP inhibitor related adverse events appeared with a similar frequency, including nausea, vomiting, fatigue, as well as anemia and thrombocytopenia, but a couple of unusual toxicities also developed. This includes hypertension in up to 20% of women, with Grade 3 to 4 hypertension in about 9%, and Grade 1 to 2 psychiatric adverse events, such as insomnia. Seven out of 751 patients treated with niraparib have developed MDS or AML, a known complication of PARP inhibitors, so blood counts should be monitored closely.

AN: Did the rate of toxicities affect dosing at all?

SB: Yes. Nearly 70% on the trial required dose interruption or reduction to manage toxicities, though drug discontinuation was infrequent. Most patients were able to titrate to a tolerable dose.

AN: To conclude, Sanjeeve, where do you see niraparib fitting in the arsenal of treatments for women with ovarian cancer?

SB: Since the efficacy of niraparib was seen in all populations on the NOVA trial, the product was granted regular approval for the treatment of women with relapsed ovarian cancer if they have responded to their regular chemotherapy. These women don’t need to be selected based on any genetic test. Please 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 at www.fda.gov/OCE.

AN: Thank you Sanjeeve. You can tweet us your questions and comments and follow us on Twitter @FDAOncology. Are there other FDA OCE approvals that you would like to hear about? Tweet us @FDAOncology. I’m Abhi Nair, and thank you for listening.

SB: And until next time at the D.I.S.C.O., 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**
			Jeannette Dinin**Nonclinical Reviewer**
			Wimolnut Manheng**Nonclinical Team Leader**
			Todd Palmby**Office of Clinical Pharmacology Reviewer(s)**
			Vadryn Pierre**Office of Clinical Pharmacology Team Leader(s)**
			Pengfei Song**Clinical Reviewers**
			Gwynn Ison and Lynn Howie**Clinical Team Leader**
			Laleh Amiri-Kordestani**Statistical Reviewer**
			Lijun Zhang**Statistical Team Leader**
			Shenghui Tang**Cross-Disciplinary Team Leader**
			Laleh Amiri-Kordestani**Associate Director for Labeling**
			William Pierce**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**
			Sharon L. Kelly, Mike Adams, Xiao Hong Chen (Lead)**Microbiology**
			Kumar Janoria, Mautang Zhou (secondary)**OPDP**
			Kevin Wright/ TL – Trung-Hieu Tran**OSI**
			Lauren Iacono-Connor/ TL – Susan Thompson**OSE/DEPI**
			Steven Bird/ Carolyn McCloskey**OSE/DMEPA**
			Tingting Gao/ TL - Alice (Chi-Ming) Tu**OSE/DRISK**
			Elizabeth Everhart/ TL- Naomi Redd**CDRH**
			Hisani Madison, Eunice Lee, Reena Philip, Soma Ghosh

OPQ=Office of Pharmaceutical Quality; OPDP=Office of Prescription Drug Promotion; OSI=Office of Scientific Investigations; OSE= Office of Surveillance and Epidemiology; DEPI= Division of Epidemiology; DMEPA=Division of Medication Error Prevention and Analysis

                                                                                  Content current as of:
      05/18/2017
              
              
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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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