Heather R. Williams, MD, assistant professor, Department of Obstetrics and Gynecology – Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, discusses the evolution of the ovarian cancer treatment paradigm over the past several decades, as well as the importance of continuing to investigate individualized treatment approaches in this population to expand therapeutic options after disease recurrence.

Patients with ovarian cancer need more therapeutic options, Williams explains. Although most patients with ovarian cancer respond to their first-line therapies, many will eventually experience subsequent disease recurrence, Williams notes. Patients with recurrent ovarian cancer have increasingly limited treatment options, according to Williams. Further research efforts need to focus on the development of additional targeted therapies that are individualized to each patients’ unique disease characteristics, Williams emphasizes. Since all ovarian cancer tumors have different genetic profiles, future investigations should also evaluate which drugs are best for each individual patient, says Williams, who adds that watching these developments unfold is exciting.

Several decades ago, the only available treatment option for patients with ovarian cancer was standard chemotherapy. Although this was an exciting therapeutic development at the time, it pales in comparison with currently available treatment approaches, including antibody-drug conjugates (ADCs) and PARP inhibitors, Williams explains. For instance, the ADC mirvetuximab soravtansine-gynx (Elahere) 

received accelerated approval from the FDA in 2022

 for patients with folate receptor α–positive, platinum-resistant ovarian cancer who have received 1 to 3 prior systemic therapies.

In addition, the PARP inhibitors olaparib (Lynparza) and niraparib (Zejula) are available in select populations. Olaparib is indicated as maintenance therapy for patients with germline 

-mutated advanced ovarian cancer who achieved a complete response (CR) or partial response (PR) with first-line platinum-based chemotherapy. Niraparib is indicated as maintenance therapy for patients with advanced ovarian cancer who experienced a CR or PR with first-line platinum-based chemotherapy, as well as in patients with germline 

-mutated recurrent ovarian cancer who had a CR or PR with first-line platinum-based chemotherapy. These relatively new agents continue to drive treatment advances for patients with this disease. Additional research with these drug classes, as well as others in development, is highly anticipated, Williams concludes.

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Heather R. Williams, MD, discusses the evolution of the ovarian cancer treatment paradigm over the past several decades, as well as the importance of continuing to investigate individualized treatment approaches in this population to expand therapeutic options after disease recurrence.

Dr Williams on the Evolution of Treatment Approaches in Ovarian Cancer

Heather R. Williams, MD, assistant professor, Department of Obstetrics and Gynecology – Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, discusses the mechanism of action of antibody-drug conjugates (ADCs) and ADC targets under investigation in patients with ovarian cancer.

ADCs are comprised of a potent chemotherapy agent that is too toxic to give in isolation, combined with an antibody that only allows the chemotherapy to be released once it enters the tumor cells, which it then kills, Williams explains. This technology will continue to provide patients with ovarian cancer with tolerable targeted therapy options, especially as researchers learn more about ADC targets that are uniquely expressed on tumor cells, according to Williams.

Many potential ADCs for patients with ovarian cancer are being evaluated in early phase 1 trials and have yet to receive official drug names, Williams says. The continued investigation of ADCs in this population is supported by the regulatory approvals for, and successful use of, ADCs in other cancer types, such as cervical cancer and multiple myeloma, Williams explains. For example, the FDA 

granted accelerated approval to the ADC tisotumab-vedotin-tftv

 (Tivdak) in 2021 for patients with recurrent or metastatic cervical cancer who experience disease progression on or after chemotherapy. In the relapsed/refractory multiple myeloma treatment landscape, the ADC 

belantamab mafodotin-blmf (Blenrep) was approved by the FDA in 2020

 for patients who have received 4 prior therapies.

The oncology treatment arena includes many targets for ADCs, Williams notes. Currently, the main ADC targets in ovarian cancer are NaPi2b and folate receptor α (FRα). The phase 1/2 UPLIFT trial (NCT03319628) investigated the NaPi2b-directed ADC upifitamab rilsodotin (XMT-1536). However, this trial 

 of investigator-assessed overall response rate in patients with NaPi2b-positive disease. For patients with FRα-positive, platinum-resistant ovarian cancer who have received between 1 and 3 prior systemic therapies, the ADC mirvetuximab soravtansine-gynx (Elahere) is approved. The 

 of this agent was supported by findings from the phase 3 SORAYA trial (NCT04296890).

Heather R. Williams, MD, discusses the mechanism of action of antibody-drug conjugates and ADC targets under investigation in patients with ovarian cancer.

Dr Williams on the Mechanism of Action of ADCs in Ovarian Cancer

Heather R. Williams, MD, assistant professor, Department of Obstetrics and Gynecology – Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, discusses ocular toxicities associated with antibody-drug conjugates (ADCs) and strategies for managing these toxicities in patients with ovarian cancer.

the ADC mirvetuximab soravtansine-gynx (Elahere) received accelerated FDA approval

 for patients with folate receptor alpha–positive, platinum-resistant epithelial ovarian, primary peritoneal, or fallopian tube cancer who have received between 1 and 3 prior therapies. This regulatory decision was supported by findings from the single-arm, phase 3 SORAYA trial (NCT04296890). In SORAYA, 41% and 6% of patients experienced any-grade and grade 3/4 treatment-related blurred vision, respectively. Additionally, the prescribing information for mirvetuximab soravtansine includes a boxed warning for ocular toxicities, including keratopathy, visual impairment, photophobia, dry eye, uveitis, and dry eye.

Among patients with ovarian cancer who experience eye toxicities from mirvetuximab soravtansine, most experience blurred vision, Williams says. Patients receiving this ADC are required to use steroid or lubricating eye drops daily and keep a daily log detailing when they use eye drops to mitigate some ocular toxicities, Williams notes.

More severe eye toxicities, such as keratopathy, need to be monitored for by patients’ ophthalmologists, Williams explains. Patients are required to visit their eye doctor prior to initiating treatment with mirvetuximab soravtansine, as well as after the first few treatment cycles, to maintain eye health Williams emphasizes. Although collaboration between gynecologic oncologists and ophthalmologists is not typical, this multidisciplinary approach to patient care is important when using ADCs, according to Williams.

Patient and caregiver education about the risk of developing these adverse effects associated with ADCs is also crucial, Williams notes. As evidenced by the successful use of ADCs in patients with other tumor types, patients are usually able to manage eye drops and other preventive measures, Williams concludes.

Heather R. Williams, MD, discusses ocular toxicities associated with antibody-drug conjugates and strategies for managing these toxicities in patients with ovarian cancer.

Dr Williams on Eye Toxicities Associated With ADCs in Ovarian Cancer

Heather R. Williams, MD, gynecologic oncologist, the Winthrop P. Rockefeller Cancer Institute, assistant professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, the University of Arkansas for Medical Sciences, discusses the importance of further exploring the use of antibody drug conjugates (ADCs) in ovarian cancer, specifically highlighting the investigation of mirvetuximab soravtansine in this population.

® State of the Science Summit™, Williams and colleagues from the University of Arkansas for Medical Sciences each gave presentations on topics spanning gynecologic cancer treatment. Williams presented information on the phase 3 SORAYA trial (NCT04296890) and the phase 3 MIRASOL trial (NCT04209855), in patients with ovarian cancer. The single-arm SORAYA trial investigated the use of mirvetuximab soravtansine inpatients with platinum-resistant disease harboring a high level of folate receptor α (FRα), and the MIRASOL trial evaluated the use of mirvetuximab soravtansine vs investigator's choice of chemotherapy in the same patient population.

Data from both phase 3 trials confirm the tolerability of mirvetuximab soravtansine in patients with FRα-high platinum-resistant ovarian cancer, Williams begins. In the MIRASOL trial, investigators noted that patients’ disease responded better to mirvetuximab soravtansine than to standard chemotherapy, Williams explains.

Heavily pretreated patients with progressive disease, such as those enrolled in SORAYA and MIRASOL, may experience several symptoms that come from their disease itself, rather than from their therapy, Williams notes. Furthermore, chemotherapy is associated with toxicities that lead to significant adverse effects (AEs), she emphasizes.

The treatments patients receive for their ovarian cancer should not be more difficult to tolerate than their disease itself, Williams continues. Mirvetuximab soravtansine, with its tolerable safety profile, addressed this previously unmet need, according to Williams. However, ADCs are associated with AEs that should be watched for, as they are unique from those seen with chemotherapy, Williams says. However, patients respond well to ADCs, and the safety profiles of these agents are not worse than those of other options in the landscape, including standard chemotherapy, Williams concludes.

Heather R. Williams, MD, discusses the importance of further exploring the use of antibody drug conjugates in ovarian cancer, specifically highlighting the investigation of mirvetuximab soravtansine in this population.


Dr Williams on the Importance of Investigating ADCs in Ovarian Cancer

Heather R. Williams, MD, assistant professor, Department of Obstetrics and Gynecology – Division of Gynecologic Oncology, University of Arkansas for Medical Sciences, discusses findings from the phase 3 PRIMA trial (NCT02655016) in patients with ovarian cancer.

PRIMA evaluated the efficacy and safety of the PARP inhibitor niraparib (Zejula) vs placebo as maintenance therapy in patients with newly diagnosed advanced ovarian cancer who had responded to first-line platinum-based chemotherapy. In total, 373 of 733 patients who were randomly assigned in this trial had homologous repair–deficient (HRD) tumors; 223 patients had 

In this trial, treatment with niraparib led to a survival benefit compared with placebo across all prespecified subgroups, Williams says. In the entire population, the median progression-free survival (PFS) was 13.8 months and 8.2 months with niraparib and placebo, respectively (HR, 0.62; 95% CI, 0.50-0.76; 

 < .001). The median PFS in the HRD subgroup was 21.9 months with niraparib and 10.4 months with placebo (HR, 0.43; 95% CI, 0.31-0.59; 

Additionally, the interim overall survival (OS) analysis showed estimated 24-month OS rates of 84% and 77% in the niraparib and placebo arms, respectively, in the overall population (HR, 0.70; 95% CI, 0.44-1.11). In the HRD subgroup, the estimated 24-month OS rate was 91% with niraparib vs 85% with placebo. Although the estimated OS benefit with niraparib was modest in this subgroup, this agent still provided a benefit in the HRD population, which has limited treatment options, Williams notes.

Based on these findings, frontline niraparib maintenance therapy was 

 for patients with advanced ovarian cancer who have responded to platinum-based chemotherapy.

Subsequently, at a median follow-up of 3.5 years, the median investigator-assessed PFS in the overall population was 13.8 months with niraparib vs 8.2 months with placebo (HR, 0.66; 95% CI, 0.56-0.79). Furthermore, the median investigator-assessed PFS in the HRD subgroup was 24.5 months with niraparib vs 11.2 months with placebo (HR, 0.52; 95% CI, 0.40-0.68).

Heather R. Williams, MD, discusses findings from the phase 3 PRIMA trial in patients with ovarian cancer.

Heather R. Williams, MD

Articles

Dr Williams on the Evolution of Treatment Approaches in Ovarian Cancer

Dr Williams on the Mechanism of Action of ADCs in Ovarian Cancer

Dr Williams on Eye Toxicities Associated With ADCs in Ovarian Cancer

Dr Williams on the Importance of Investigating ADCs in Ovarian Cancer

Dr Williams on Frontline Niraparib Maintenance Therapy in Ovarian Cancer