Awareness and Early Detection Remain Key Issues in Ovarian Cancer

Vaidehi Mujumdar, MD

World Ovarian Cancer Day is an initiative set forth by the World Ovarian Cancer Coalition, which aims to highlight the importance of educating clinicians, researchers, and patients with the goal of closing the gaps that remain in health care systems to enable timely access to diagnostic tests and improve care for this patient population.¹

On World Ovarian Cancer Day, Vaidehi Mujumdar, MD, sat down with OncLive® to discuss the importance of personalized medicine and tailored approaches for improved outcomes for patients with ovarian cancer. Despite advancements, ongoing challenges persist, emphasizing the need for continued research and collaborative efforts that enhance early detection tools and treatment options.

“Ovarian cancer incidence is down,” Mujumdar explained. “However, we know that we don't have the best diagnostic tools for early detection, but we can prevent or reduce the risk via opportunistic salpingectomy when work in tandem with our surgical and obstetrics/gynecology colleagues. We [also] need more funding for clinical trials that allow us to bring better treatment options for all of our patients.”

In the interview, Mujumdar emphasized the importance of continuing to raise awareness about ovarian cancer; highlighted prevention strategies and symptom detection; and discussed significant advancements that have pushed the ovarian cancer treatment landscape forward. Mujumdar is a first-year gynecology oncology fellow at Atrium Health Levine Cancer in Charlotte, North Carolina.

OncLive: Can you explain why raising awareness about ovarian cancer is particularly crucial on this awareness day?

Mujumdar: Ovarian cancer is one of the leading causes of cancer deaths among women. Individuals with ovaries have a 1 in 87 lifetime risk of getting ovarian cancer, and then a 1 in 130 lifetime chance of dying from ovarian cancer.² Those statistics don't take into account anything other than high-grade serous ovarian cancers, which are the most common. We know that [ovarian cancer] develops in older women, and half of women who are diagnosed with ovarian cancer are 63 years of age or older. Although the rate of ovarian cancer death has been decreasing, we still have a lot of progress to make.

Ovarian cancer was historically called the silent killer because we didn’t—and we still don't—have a great diagnostic tool for catching ovarian cancer early, such as we do with pap smears and HPV testing for cervical dysplasia.

It’s important to point out that ultrasounds and lab testing cannot accurately detect ovarian cancer; therefore, it's important to educate patients and the public about symptoms early on.

How can awareness initiatives help address these challenges that patients with ovarian cancer face?

Symptoms of ovarian cancer can be very non-specific. A few [include] bloating; feeling full after eating a small amount; difficulty eating; back pain; pressure in your pelvis or abdomen; changes with urination; changes in bowel [movements]; and constipation. A lot of these, if we asked any person, they would probably say they had those [symptoms] at some point in their life. The big issue is: Are those symptoms different from your baseline? Are they persisting? It's about getting a patient in to see a gynecologist to see if there are any abnormalities that prompt a patient to come see a gynecologic oncologist.

Prevention and risk reduction is a big deal with ovarian cancer. What I mean by that is opportunistic salpingectomy, which is the surgical removal of the fallopian tubes in tandem with a cesarean section, cyst removal, or other abdominal surgery. This would be [for patients] who have completed childbearing. [Opportunistic salpingectomy] can be done routinely, and it's something that we have done [in recent years]. The reason for [opportunistic salpingectomy] is the full removal and histological examination of the fimbriae, which can improve disease outcomes because mutations in high-grade serous ovarian cancer through the P53 tumor suppressor gene occur at a high rate in that fimbriated end.

There's a clinical trial called the SOROCk study [NCT04251052] that is open to individuals who have BRCA1 mutations. For these pre-menopausal patients, [the goal of this study is to see] whether the removal of the fallopian tubes with a plan to remove the ovaries at a later time can reduce the risk of ovarian cancer to the same degree as the standard of care, which is removing both the ovaries and the fallopian tubes. When we talk about awareness, it's about knowing these things and being able to speak to your gynecologist, surgeons, or other doctors about them.

Kara Long Roche, MD, MSc, FACOG, of Memorial Sloan Kettering Cancer Center, in New York, New York, [describes] ovarian cancer as a dandelion that you're blowing out, and you're watching all the seeds just spread everywhere in the belly. Because the fallopian tube is open to the abdomen, you can imagine that once that seed is blown, it's everywhere. That's what makes it hard to treat once the cancer has spread. Prevention or risk-reducing surgeries with the fallopian tubes are a great, ideal way to stop that [spread] from happening.

If a patient unfortunately does get ovarian cancer, understanding risk factors and symptom recognition [is important]. Ultimately, it remains important for these patients to be tied in with survivorship groups and advocacy groups that are going to help them through that process.

How has increased awareness impacted the early detection and treatment for patients with ovarian cancer in recent years?

Increased awareness has had a positive impact on getting funding for clinical trial research, which has helped with having risk-reducing surgery and early detection. Improved symptom recognition is something that I've seen. From an anecdotal viewpoint, people in the community are a little bit more aware of what those symptoms may be or that they're not normal if they persist for a while, and [they know] to talk to their doctor about that. I had patients come to me even as a resident and ask about some of these symptoms because they were worried. Additionally, advancements in imaging technologies have helped [with detection and treatment].

Regarding treatment options, PARP inhibitors have changed the landscape for patients with recurrent ovarian cancer, especially those harboring BRCA mutations. Since more than 75% of patients with ovarian cancer present with advanced disease, and 85% of those patients [experience disease recurrence], the ability to achieve remission and extend progression-free survival [PFS] and overall survival [OS] is still a high unmet need.

We've had multiple trials that have established the utility of PARP inhibitors as the new standard of care for those patients with both germline and somatic BRCA mutations or with homologous recombination deficiency [HRD].

What are some key trials that have helped shift the ovarian cancer treatment paradigm?

In 2018, [data from] the phase 3 SOLO-1 trial [NCT01844986] led to [the FDA approval] of olaparib [Lynparza] in the United States, and it was the first PARP inhibitor [indicated] for first-line maintenance therapy in patients with germline and somatic BRCA mutations.³ We had subsequent phase 3 trials, including PRIMA [NCT02655016], PAOLA-1 [NCT02477644], ARIEL3 [NCT01968213] and ATHENA-MONO trial [NCT03522246], and those evaluated the use of first-line PARP inhibitors in patients beyond the BRCA-mutated population and used combination treatments with bevacizumab [Avastin].

PRIMA led to the 2020 FDA approval of niraparib [Zejula], regardless of biomarker status⁴; PAOLA-1 led to the approval of the olaparib and bevacizumab combination in patients with HRD-positive advanced ovarian cancer, including patients with BRCA mutations.⁵ In December 2022, the FDA limited the use of rucaparib [Rubraca] in the second-line setting and beyond for only patients harboring BRCA mutations.⁶

At the 2023 ESMO Congress, investigators presented [data for] senaparib [IMP4297] from the phase 3 FLAMES trial [NCT04169997]. That PARP inhibitor improved PFS [vs placebo] in all comers with advanced ovarian cancer who have responded to frontline platinum-based chemotherapy [HR, 0.43; 95% CI, 0.32-0.58; P < .0001].⁷ We don't know if we're going to embrace yet another PARP inhibitor in the oncology community, but it does appear that senaparib has activity in the maintenance setting across all comers with ovarian cancer, and it is a promising agent.

What role does personalized medicine, such as genomic testing and precision oncology, play in the diagnosis and treatment of patients with ovarian cancer?

Genomic testing to analyze the genetic makeup of a tumor and identify specific mutations or alterations is where we've been moving for a while in ovarian cancer. Genomic testing could identify those mutations that we care about, such as BRCA and others, that will influence a lot of our treatment decisions and prognosis for patients. Additionally, genomic testing can help identify other molecular targets or pathways that can be exploited for treatment. That's going to lead to more personalized and effective therapies.

In terms of precision oncology, using that genomic information along with clinical and molecular data is going to tailor our strategies to individual patients. One of the points to mention is the integration of next-generation sequencing [NGS] into ovarian cancer management. Rather than solely focusing on specific mutations, such as just focusing on BRCA, NGS can provide a comprehensive view of the genetic landscape of the tumors. This will give us insight into those therapeutic targets and pathways, as well as a more nuanced understanding of individual tumors; that's going to help target the genetic profile for each patient.

Why do we care about that? [This information] is going to lead to better response rates, longer PFS, and improved OS for these patients.

What challenges do patients with ovarian cancer still face throughout their treatment journey? How would you like to see health care providers and professionals better support them throughout these challenges?

With any cancer diagnosis, and especially with ovarian cancer, which ends up being a chronic disease for a lot of our patients that they must continue to live with, there is a big emotional and psychological impact as they manage those symptoms and adverse effects over the course of long-term treatment.

One of the things that I care about is the financial burden of a cancer diagnosis, especially with ovarian cancer. This can't be stated enough. The cost of cancer care in [the United States] can be debilitating, including medical expenses, medications, and supportive care services. There are ways to mitigate [these financial burdens], such as navigating insurance coverage and accessing financial assistance programs that a lot of centers have. [Patients can be assisted by] social workers, financial counselors, and patient advocacy organizations.

Beyond that, clearer communication can help patients feel more empowered and involved in their treatment decisions. Clinical trials are key for so many of our patients, but we do have to continue to address the racial disparities when it comes to ovarian cancer and trial enrollment. [These disparities are not limited to] just ovarian cancer.

In the last couple of years, there have been several studies involving patients with different cancer types, including ovarian, that have identified a notable disparity in genetic testing utilization, disease stage at the time of diagnosis, and adherence to treatment guidelines between Black patients and non-Hispanic White patients, which ultimately leads to increased mortality rates among people of color. That's a huge issue.

There are multiple determinants [that drive these disparities], such as implicit bias, mistrust of the health care system, accessibility issues, and socioeconomic influences. We need to have a deeper understanding of our diverse patient perspectives and identify barriers that are going to help those patients receive optimal care and participate in clinical trials.

References

1. World Ovarian Cancer Day. International Gynecologic Cancer Society. Accessed May 7, 2024. https://igcs.org/world-ovarian-cancer-day
2. Key statistics for ovarian cancer. American Cancer Society. January 19, 2024. Accessed May 7, 2024. https://www.cancer.org/cancer/types/ovarian-cancer/about/key-statistics.html
3. FDA approved olaparib for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based. News release. FDA. December 19, 2018. Accessed May 7, 2024. https://www.fda.gov/drugs/fda-approved-olaparib-lynparza-astrazeneca-pharmaceuticals-lp-maintenance-treatment-adult-patients
4. FDA approves niraparib for first-line maintenance of advanced ovarian cancer. News release. FDA. April 29, 2020. Accessed May 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer
5. FDA approves olaparib plus bevacizumab as maintenance treatment for ovarian, fallopian tube, or primary peritoneal cancers. News release. FDA. May 8, 2020. May 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-plus-bevacizumab-maintenance-treatment-ovarian-fallopian-tube-or-primary 
6. United States Securities and Exchange Commission form 8-K. Clovis Oncology. December 2022. Accessed May 7, 2024. https://d18rn0p25nwr6d.cloudfront.net/CIK-0001466301/c27075d6-6d64-42e0-af52-a7b855dc2748.pdf
7. Wu X, Liu J, Wang X, et al. Efficacy and safety of senaparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer (FLAMES): a randomized, double-blind, placebo-controlled, phase 3 trial. Ann Oncol. 2023;34(suppl 2):S1277-S1288. doi:10.1016/j.annonc.2023.10.030