Naumann Spotlights Expanding Arsenals and Evolving Decision-Making in Platinum-Resistant Ovarian Cancer

R. Wendel Naumann, MD

Although the recent expansion of FDA-approved therapies for patients with platinum-resistant ovarian cancer signals an ongoing shift in disease management, particularly for those with specific molecular profiles, difficulties navigating and selecting the optimal therapies for rare disease subtypes, such as clear cell ovarian adenocarcinoma, still exist, according to R. Wendel Naumann, MD, who emphasized the need for novel treatment strategies and enrollment in clinical trials to address unmet needs for these patient subgroups.

In March 2024, the FDA granted full approval to mirvetuximab soravtansine-gynx (Elahere) for patients with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have previously received 1 to 3 systemic treatment regimens. This regulatory decision was based on data from the phase 3 MIRASOL study (Study 0416; NCT04209855), in which the antibody-drug conjugate (ADC; n = 227) produced a median overall survival (OS) of 16.5 months (95% CI, 14.5-24.6) vs 12.7 months (95% CI, 10.9-14.4) with investigator's choice of chemotherapy (n = 226; HR, 0.67; 95% CI, 0.50-0.88; P = .0046). The agent also improved progression-free survival (PFS) vs chemotherapy (HR, 0.65; 95% CI, 0.52-0.81; P < .0001).¹

“These [ADCs] are highly effective in the platinum-resistant setting and are our best option for approved medications,” Naumann said in an interview with OncLive^® following an OncLive State of the Science Summit (SOSS)™ on gynecologic oncology, which he chaired.

In the interview, Naumann expanded on 2 case studies of platinum-resistant ovarian cancer histologies that were presented by his colleagues at the SOSS, discussed appropriate treatment avenues according to patient characteristics, and noted recent FDA approvals that have expanded treatment options and improved the management of these rarer disease subtypes.

Naumann is a gynecologic oncologist at Atrium Health Levine Cancer Institute and a clinical professor of Obstetrics and Gynecology at Wake Forest University School of Medicine in North Carolina.

OncLive: OncLive: Please describe the first case study of a 65-year-old patient with high-grade serous fallopian tube carcinoma that was presented by Brittany Lees, MD, during the meeting.

Naumann: The patient had BRCA-positive, high-grade serous fallopian tube cancer. She had been treated with multiple lines of platinum-based chemotherapy, but unfortunately became platinum resistant. At that point, treatment options are fairly limited, and she received a standard platinum-resistant regimen of liposomal doxorubicin and bevacizumab [Avastin]. After that, we didn’t have a lot of good treatment options until recently. This patient did have a very high FRα expression in 90% of her cells at 2+ [intensity] or more. Mirvetuximab soravtansine is an excellent drug in this setting, and is FDA approved for patients who have 2+ expression of FRα in more than 75% of their cells.

In the initial [phase 3 SORAYA trial (NCT04296890) supporting the agent’s] accelerated approval, there was a [31.7%] response rate. In the [confirmatory] MIRASOL study, [which supported the agent’s] final approval, it beat standard chemotherapy options in terms of PFS and OS. [Mirvetuximab soravtansine] is probably the best drug for this patient at the current time. This is an antibody-drug conjugate [ADC] and a microtubule inhibitor [conjugate]. These [ADCs] are highly effective in that setting, and are our best option with approved medications.

Regarding Dr Lee’s second case presentation, what treatment approaches were considered by the panel for the patient with clear cell ovarian adenocarcinoma?

This was a case of the rare ovarian epithelial cancer, clear cell ovarian cancer. This patient initially responded to chemotherapy, although these cancers tend to be more chemoresistant than other cancers. We don’t have a lot of good treatment options for these patients other than standard chemotherapy. However, these patients are more likely to respond to either immunotherapy or treatment with bevacizumab.

There’s some interest in doing match trials as well as trials that have multiple arms in rare tumors where we try to evaluate multiple different therapies. From a traditional chemotherapy standpoint, that’s probably not the optimal choice for these patients. We discussed the role of either single-agent PD-1 inhibitors or a combination of PD-1 and CTLA-4 inhibitors, which can have fairly dramatic responses in patients with clear cell ovarian cancer. However, we don’t have a lot of good data for these patients so we’re looking for new, active regimens.

What is the importance of facilitating these case discussions in the gynecologic oncology field?

Immunotherapy plus chemotherapy in the upfront setting is likely the biggest [conversation to have] for almost all patients. [However], our success has now led to some uncertainty in the recurrent setting because the types of treatments that patients have been exposed to are different than what patients [have had] in the recurrent setting, particularly with respect to lenvatinib and pembrolizumab. We [still] have a lot of discussions regarding who should be treated with lenvatinib and pembrolizumab. [The combination is] our best option in the second-line setting, but [the trials supporting its use] included patients who were not [previously exposed to a] PD-1 [inhibitor]. Therefore, we don’t know how effective it’s going to be [in this patient subgroup].

[Lastly,] we have a new option for our patients with high HER2 expression, and there are other ADCs out there that look promising and [will likely] be used in the endometrial space. Hopefully, the trials [evaluating these agents] will mature in the future.

Reference

FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. March 22, 2024. Accessed May 7, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian