Advances With Systemic Therapy and Surgery Underscore the Need for Multidisciplinary Care in Ovarian Cancer

Stephen L. Rose, MD

Utilizing a multidisciplinary approach to care is critical in the field of ovarian cancer with the substantial advancements that have been made with systemic chemotherapeutic regimens, PARP inhibitors, maintenance therapy, and surgical interventions, according to a panel of experts from the Carbone Cancer Center of the University of Wisconsin (UW) School of Medicine and Public Health that presented during an OncLive^® Institutional Perspectives in Cancer webinar on ovarian cancer.

Notably, the chair of the event, Stephen L. Rose, MD, director of the UW Gynecologic Oncology program in the Department of Obstetrics and Gynecology at the UW Carbone Cancer Center, and panelists highlighted that treatment selection should be multifaceted and based on several patient and disease factors to optimize treatment for patients.

“When there is collaboration, it is like a tango. The collaboration between medical oncologists and surgical oncologists is pivotal to be continuous. Early consultation in a timely fashion is helpful,” said panelist Ahmed N. Al-Niaimi, MD, an assistant professor of obstetrics and gynecology at the UW School of Medicine and Public Health during the meeting.

Rose and Niaimi were joined by fellow faculty:

• Alissa Weber, MD, hematologist/oncologist, SSM Health
• Ryan J. Spencer, MD, FACOG, assistant professor, Division of Gynecologic Oncology, UW School of Medicine and Public Health, director, Obstetrics and Gynecology Residency Program, associate director, Gynecologic Oncology fellowship-training program, UW Carbone Cancer Center
• Ellen M. Hartenbach, MD, vice chair, Education and Faculty Development, Department of Obstetrics and Gynecology, professor, Division of Gynecologic Oncology, UW School of Medicine and Public Health
• Lisa A. Barroilhet, MD, Dolores A. Buchler, MD, Faculty Fellow in Gynecologic Oncology, assistant professor of medicine, UW School of Medicine and Public Health, leader, Disease Oriented Work Group for Gynecologic Malignancies, UW Carbone Cancer Center

During the meeting, the panelists spoke to the current role of genetic and molecular testing in women with ovarian cancer, best practices for navigating first- and second-line maintenance treatment selection, current surgical options for newly diagnosed disease, and emerging strategies for patients with recurrent disease.

Genetic/Molecular Testing in Ovarian Cancer

Weber: As the list of ovarian cancer–associated genes and available targeted therapies continues to grow, the field’s knowledge of germline and somatic mutation status is becoming increasingly important in the management of ovarian cancer. It’s understood that up to 1 in 4 women harbor germline mutations and 5% to 7% of patients will have somatic homologous recombination deficiency [HRD].

PARP inhibitors have transformed the treatment of patients with germline BRCA mutations; however, their utility extends beyond BRCA with different magnitudes of therapeutic benefit in patients with HRD-positive disease, for example. As such, widespread and routine testing for HRD status should be supported in clinical practice, as is the case with HER2 and EGFR testing.

Frontline Maintenance Therapy

Spencer: In the frontline setting, PARP inhibitors used as maintenance therapy have demonstrated a survival advantage for patients with ovarian cancer. Olaparib [Lynparza] improved progression-free survival [PFS] in patients with BRCA mutations and niraparib [Zejula] improved PFS across the BRCA/homologous recombination spectrum. However, the PFS benefit was less pronounced with niraparib among patients with homologous recombination–proficient [HRP] ovarian cancer.

The combination of olaparib and bevacizumab [Avastin] also demonstrated a PFS benefit across the BRCA-mutated/HRD spectrum when used as maintenance therapy; however, no PFS improvement was demonstrated with the doublet in patients with HRP ovarian cancer.

Second-Line Maintenance Therapy

Hartenbach: When selecting patients for second-line maintenance therapy, patient preference should be considered vs active surveillance. Additionally, the patient’s history of first-line maintenance therapy with PARP inhibitors and/or bevacizumab should be taken into consideration. Cancer histology should also be considered when selecting second-line maintenance therapy because PARP inhibitors benefit patients with high-grade serous and endometrioid disease.

Patients who did not receive prior PARP inhibitors are good candidates for PARP inhibitor switch maintenance therapy after they have derived a response to a platinum-based therapy. Patients who received a PARP inhibitor in the first-line maintenance setting without bevacizumab are good candidates for bevacizumab maintenance in the second-line setting.

Second-line PARP inhibitor maintenance may be preferred over first-line PARP inhibitor maintenance because even patients with HRP ovarian cancer can benefit from niraparib, as shown in the NOVA trial [NCT01847274], or from rucaparib [Rubraca], as shown in the ARIEL3 trial [NCT01968213].

Retreatment with bevacizumab in the second-line maintenance setting has demonstrated some success in the MITO16MANGO2b trial [NCT01802749], as has retreatment with PARP inhibitors in the OReO trial [NCT03106987].

Surgical Options in Newly Diagnosed Ovarian Cancer

Al-Niami: Although systemic chemotherapies and PARP inhibitors have revolutionized ovarian cancer management, cytoreductive surgery has a similar role for these patients and can elicit good responses. Moreover, hyperthermic intraperitoneal chemotherapy [HIPEC] surgery also has utility, but high-pressure HIPEC is being evaluated in clinical studies, further underscoring the need for multidisciplinary care. Collectively, HIPEC, PARP inhibitors, and maintenance therapy options will continue to extend survival for patients with ovarian cancer.

Recurrent Ovarian Cancer

Barroilhet: The treatment of patients with recurrent ovarian cancer has been an area of growth, and survival has improved with available chemotherapy-based therapies. Additionally, in patients with platinum-sensitive disease, pembrolizumab [Keytruda] may be considered for patients with microsatellite instability–high tumors.

However, several oral therapeutic options are emerging, such as AVB500, berzosertib, adavosertib, and DMUC4064A. Moreover, a slew of ongoing clinical trials evaluating novel therapies in patients with platinum-resistant or platinum-sensitive ovarian cancer are ongoing and currently enrolling patients.