Expert Identifies Biggest Shifts in Ovarian Cancer Paradigm

Jonathan S. Berek, MD, MMS

Jonathan S. Berek, MD, MMS

The field of ovarian cancer has significantly evolved since the International Federation of Gynecologists and Obstetricians (FIGO) revised the staging system to account for the heterogeneity in epithelial tumors that arise from the ovaries, fallopian tubes, or peritoneum.

This is a revision, explained Jonathan S. Berek, MD, MMS, that has been augmented by a rise in genetic testing and novel therapies, such as PARP inhibitors.

“Being able to take a couple of tablets every day is a great improvement in quality of life,” said Berek. “The goal is to get more customized targeted therapies that are well tolerated, so people can live longer and better lives.”

The impact of PARP inhibitors has been extensive, he added. Presently, all 3 PARP inhibitors—–niraparib (Zejula), olaparib (Lynparza), and rucaparib (Rubraca)––are indicated as maintenance treatment for women with a complete or partial response to platinum-based chemotherapy.

Most recently, olaparib demonstrated a significant improvement in progression-free survival (PFS) as frontline maintenance for women with BRCA-positive advanced ovarian cancer. In the phase III SOLO-1 trial, findings of which were presented at the 2018 ESMO Congress, the investigator-assessed PFS had not yet been reached with olaparib versus 13.8 months with placebo at a median follow-up of 41 months. Based on these data, the FDA granted a priority review designation to olaparib in this setting for patients with newly diagnosed, BRCA-positive advanced ovarian cancer.

OncLive^®: What genes predispose individuals to ovarian cancer?

What are the various histopathologies of this disease?

Have there been any updates to the staging system?

What agents did you highlight in your presentation? Which ones have made the biggest shift in treatment?

In an interview during the 2018 OncLive^® State of the Science Summit^TM on Ovarian Cancer, Berek, the Laurie Kraus Lacob Professor at Stanford Medicine, director of the Stanford Women’s Cancer Center, and senior advisor at Stanford Cancer Institute, outlined the changing paradigm of ovarian cancer.Berek: Carrying a germline mutation is a risk factor for developing the disease. However, that is something that we can better detect now based on family history [and the rise in] testing. We're testing everybody who comes to the center with a diagnosis of ovarian cancer for any genetic background, so that they have the information [to inform] potential treatment with PARP inhibitors or to advise their family.The most common type is high-grade serous carcinoma (HGSC). The treatments vary to some extent based on the different types of histology. At this point, there are probably not enough specific targeted therapy to allocate based on [histology]. For example, we treat mucinous tumors differently. Recently, there has been an effort to treat patients with endometrioid clear cell [carcinoma] somewhat differently. We're treating low-grade serous carcinomas differently than we do HGSC. HGSC makes up about 85% of all ovarian, fallopian tube cancers; they're the ones that are responsive to PARP inhibitors.Yes and no. The last one was made in 2014. The main change was that we no longer stage ovarian cancer. We call it ovarian, fallopian tube, and peritoneal cancer because it's really all one disease.I introduced the subject of the PARP inhibitors and the angiogenesis blockers, as well as early trials with immune therapies.

Even with all of these advances, what would you like to see break into the landscape?

Are there any ongoing clinical trials at Stanford Medicine that you would like to highlight?

The PARP inhibitors are the ones that are shifting the treatment paradigm. We have evidence now that several of them are effective as maintenance therapy for women after first-, second-, or third-line therapy [for] those who have responded to platinum-based chemotherapy. Any high-grade serous tumor—even if it isn’t associated with a BRCA1/2 mutation—has been responsive to PARP inhibitors. That is a major advance. In addition, they're generally well tolerated; they're oral medications, so they're portable.We want to cure people more frequently than we do. We don't cure the majority of patients with advanced ovarian cancer. As you know, most people present with advanced disease. We don't have a means for early detection. We don't have an effective way to diagnose the disease before it has spread in most cases. Eighty percent to 90% of the time, it has already spread, which makes the prognosis more challenging and the treatment more difficult.We're doing trials with PARP inhibitors in combination with checkpoint inhibitors. We're also doing a number of immunotherapy trials alone. We have a couple of vaccine trials as well. Those are all very exciting studies. We recently had one where we had some excellent responses.

Moore K, Colombo N, Scambia G, et al. Olaparib maintenance therapy following first-line platinum-based chemotherapy in patients with FIGO stage III—IV ovarian cancer (OC) with a BRCA1/2 mutation (BRCAm): phase III SOLO1 trial. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA7_PR.