Douglas A. Levine, MD
While precision medicine has been a modern go-to approach by physicians in various malignancies, it is demonstrating a particular benefit in ovarian cancer, especially using the method for clinical trial enrollment and in determining whether patients are eligible to receive treatment with PARP inhibitors, according to Douglas A. Levine, MD.
For example, updated findings of a phase II trial presented at the 2017 ASCO Annual Meeting demonstrated that the combination of the PARP inhibitor olaparib (Lynparza) and the angiogenesis inhibitor cediranib maleate continued to show superior progression-free survival (PFS) versus olaparib alone for women with BRCA
-negative recurrent platinum-sensitive ovarian cancer.
In the updated analysis, which was conducted after 67 PFS events, median PFS continued to favor the combination over monotherapy at 16.5 months versus 8.2 months, respectively (HR, 0.50; P
= .007). Specifically, in patients without a known germline BRCA
mutation, the updated median PFS was still superior in the cediranib/olaparib arm compared with monotherapy at 23.7 months versus 5.7 months (HR, 0.32; P
Additionally, an ongoing phase II trial is exploring the safety and efficacy of TPIV200/huFR-1, a multi-epitope antifolate receptor vaccine in combination with the PD-L1 inhibitor durvalumab (Imfinzi) in patients with platinum-resistant ovarian cancer (NCT02764333).
In an interview with OncLive
, Levine, professor, Department of Obstetrics and Gynecology, director, Division of Gynecologic Oncology, NYU Langone's Perlmutter Cancer Center, shared his insight on how the ovarian cancer landscape has developed a more personalized treatment approach. Levine co-chaired the 2017 OncLive®
State of the Science SummitTM
on Treatment Options in Ovarian Cancer, where he discussed the topic in greater detail.
OncLive: Can you provide an overview of your lecture?
: I talked about incorporating precision medicine into gynecologic cancers, particularly in ovarian cancer. I began by talking about different sequencing methods and how far we've come with sequencing from the Human Genome Project to The Cancer Genome Atlas Project and the application of sequencing and precision medicine in daily clinical care. Specifically, we gave some examples of how to use precision medicine to direct people toward clinical trials, both for ovarian cancer and endometrial cancer, and how to use precision medicine to stratify patients for treatment with PARP inhibitors.
What are the sequencing challenges currently being faced in the ovarian cancer landscape?
The good thing about precision medicine is that doing the actual sequencing is quite easy nowadays. We've gotten pretty good at sequencing, and there are some established laboratories [that are also good] at interpreting the sequencing. Now, it is the interpretation that remains much more challenging than the actual sequencing.
Laboratories that have been around for a long time do this quite well. In some of the newer commercial labs, it is very important to figure out how the validation is done and make sure the details of the sequence analysis are done properly, which sometimes can be difficult to figure out. As far as doing the sequencing, we can now use sequencing to determine what mutations are in a patient's tumor and then to direct that patient toward a clinical trial or possibly for off-label use of clinical therapies.
What has it been like for you to see the paradigm transforming to include a more precision medicine approach?
Precision medicine has really been successful in part due to the importance of genetic testing for BRCA 1/2
mutations. That got the concept of sequencing into the clinic and to the patient population. Now, patients are coming in saying, “I want BRCA 1/2
sequencing.” Once we became familiar with that type of sequencing, it wasn’t a big stretch from sequencing the germline to sequencing the tumors. Once we could sequence the tumors, people then became familiar with targeted therapies. Certainly, the FDA approvals of various PARP inhibitors have turned sequencing into an everyday event.
Speaking of PARP inhibitors, can you discuss their utility and selecting patients to receive them?
The PARP inhibitors do have different approved indications. Some are approved in the maintenance setting and some for active treatment or treatment of active disease. The PARP inhibitors themselves are similarly efficacious; they all work quite well. They all work the best in women who have BRCA
mutations. They work second best in women who have dysfunction in DNA repair.