Ryan M. Kahn, MD, MHS, FACOG
As surgical modalities and treatments for ovarian cancer continue to advance, an additional research emphasis is necessary to address ongoing challenges and unmet needs in the space through the development of potentially practice-changing treatments, according to Ryan M. Kahn, MD, MHS, FACOG.
Treatments, such as mirvetuximab soravtansine-gynx (Elahere), have reshaped the treatment paradigm for ovarian cancer, namely with the FDA approval of the treatment in March 2024 of the agent in patients with folate receptor alpha (FRα)–positive, platinum-resistant ovarian cancer.1
“When ovarian cancer recurs, a lot of times it becomes platinum-resistant or refractory, and a lot of options aren’t as effective for patients in this setting,” Kahn explained in an interview with OncLive® during Ovarian Cancer Awareness Month, observed annually in September. “What mirvetuximab soravtansine has given physicians and patients is another option that can be very responsive, even to a disease that hasn’t been responsive to a lot of medications before. This is a very exciting time.”
Kahn is a gynecologic oncologist at Baptist Health Miami Cancer Institute in Florida.
In the interview, Khan highlighted the evolution of surgical modalities in ovarian cancer, minimally invasive approaches in gynecologic cancers, and ongoing challenges and unmet needs from a surgical standpoint. Furthermore, Kahn discussed the phase 3 MIRASOL study (NCT04209855) that evaluated mirvetuximab soravtansine for the treatment of patients with FRα-positive, platinum-resistant ovarian cancer.
OncLive: How has the role of surgery evolved in the multidisciplinary management of ovarian cancer over the past decade?
Kahn: We’ve been learning that complete gross resection [CGR] at the time of either primary cytoreductive surgery or interval cytoreductive surgery gives our patients the best overall survival [OS] and provides the best prognosis for them. Over the past few decades, gynecologic oncologists have become increasingly committed to achieving CGR, which has enhanced the role of complex cytoreductive surgical procedures and has made exploration and the knowledge of expanded anatomy that much more important.
Now, gynecologic oncologists aren’t just doing hysterectomies and lymph nodes. There was a mentor of mine at Memorial Sloan Kettering Cancer Center, where I trained, who would always say, ‘We go where the cancer goes.’ Decades ago, if there was cancer in the diaphragm, spleen, pancreas, liver, or possibly in the chest, a lot of times, these patients were automatically triaged to [receive] neoadjuvant chemotherapy, and surgery wasn’t on the table for them. These days, with a lot of these improved efforts, better training, and surgical training for the gynecologic oncologist, as well as more of an emphasis on achieving CGR, we’re now able to resect a lot of this disease. We did a study during my last 2 years of fellowship looking at intrathoracic site reductions over the past 10 years. We found that not only is it safe and feasible, but patients who had CGR had a much more favorable outcome than those who were not being triaged for surgery. It’s a very exciting time as we continue to expand our surgical expertise as gynecologic oncologists.
With minimally invasive approaches on the rise, how are modalities such as laparoscopy or robotic-assisted surgeries being utilized in clinical practice?
In gynecologic oncology, minimally invasive surgery, whether it’s robotic-assisted or laparoscopic, is now widely used and widely available, and for great reasons. Patients benefit in certain situations, whether it’s expedited recovery or decreased postoperative pain. However, it should not be used in all circumstances; this is another aspect for patients to discuss with their gynecologist. In endometrial cancer, the [phase 3] study called LAP2 [NCT00002706] demonstrated that minimally invasive surgical staging for uterine cancer was feasible and safe in terms of short-term outcomes, and once again, this resulted in lower complications and shorter hospital stays than a larger open incision. This opened the door for robotic or laparoscopic use in endometrial cancer.
[However], the same results were not present in the [phase 3] LACC trial [NCT00614211], which demonstrated that minimally invasive techniques for radical hysterectomy in early-stage cervical cancers had lower disease-free survival and OS rates compared with an open abdominal approach. There are several theories as to why. There are also newer studies, such as the ROCC trial [NCT04831580], which are now reexamining this, [with] more of an emphasis on cervical containment techniques when minimally invasive procedures are utilized for the radical hysterectomy. Time will tell for cervical cancer, depending on the ROCC trial results, whether it is safe, feasible, and appropriate to use for our patients; whether it be an abdominal radical hysterectomy vs minimally invasive, these results should come out in the next few years.
What are some of the ongoing challenges in ovarian cancer from a surgical standpoint?
We discussed how important CGR is at the time of cytoreductive surgery for advanced ovarian cancer. The most difficult thing is triaging our patients. Is this a patient [for whom] we can achieve CGR, or is this a patient [for whom] CGR cannot be achieved, and they would likely have a better prognosis if they underwent neoadjuvant chemotherapy followed by surgery and postoperative chemotherapy? What makes this difficult is that the biggest factor is small bowel disease. When the ovarian cancer goes to the small bowel, a lot of times it [can lead to] miliary disease with hundreds of little ditzels across the small bowel that are unresectable. We aren’t able to take out the entire small bowel; therefore, we aren’t able to resect this disease. A lot of times, those patients are better off undergoing neoadjuvant chemotherapy to knock down miliary disease on the small bowel itself. Unfortunately, we aren’t the best at picking up disease on the small bowel on imaging. Right now, the technology isn’t there to identify this 2-mm miliary spread of ovarian cancer on the small bowel. We are working towards using algorithms, whether they’re imaging-based or patient characteristic–based, to better triage our patients.
I worked on a project during my fellowship, where we used a resectability score algorithm, which used a synoptic report from imaging as well as patient characteristics. We found that using this algorithm for our patients at the time of diagnosis of ovarian cancer was highly specific, highly sensitive, and accurate. We had a CGR rate of [approximately] 83% and a futile laparotomy rate, or a suboptimal debulk at that time, of under 5%. We can still do better, and we are trying to, whether that’s incorporating artificial intelligence or incorporating improved technology into our imaging practices to try to identify disease on the small bowel. This is something that’s going to be very important for years to come.
What is a potentially practice-changing trial in the ovarian cancer space that you are excited about?
One very exciting [approach] across most cancer types nowadays is [the use of] antibody-drug conjugates [ADCs]. One trial that was very important in ovarian cancer was MIRASOL, which [assessed] mirvetuximab soravtansine, which is an ADC that targets the FRαantigen on ovarian cancers. [This study established] that patients with ovarian cancer [n = 227] in the recurrent setting who had received 1 to 3 prior [lines of therapy] had a very high objective response rate of 42.3% [95% CI, 35.8%-49.0%] and also had a significant improvement in progression-free survival [PFS].2 The reason this is so exciting is that a lot of times when ovarian cancer is newly diagnosed, it’s very responsive and very sensitive to most chemotherapy regimens given in the frontline setting.
Mirvetuximab soravtansine was [assessed] in a highly expressive population [in terms] of FRα. A very exciting thing that’s ongoing now is that we’re starting to look at [patients with] ovarian cancer who aren’t highly expressing FRα on their cancer cells. Can they also respond in similar ways, even though the response may not be as good as the highly expressive kind? Can the PFS and OS be similar? These are questions that we’re looking to answer now as we cast a wider net to not only the highly expressive kinds, but possibly even the middle or lower expression of FRα for our patients. This is something that’s going to be coming down the [pike] the next few years [that is] important, and [research in this area] may offer new options for more patients.
References
- FDA approves mirvetuximab soravtansine-gynx for FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. FDA. March 22, 2024. Accessed September 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirvetuximab-soravtansine-gynx-fra-positive-platinum-resistant-epithelial-ovarian
- Moore KN, Angelergues A, Konecny GE, et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med. 2023;389(23):2162-2174. doi:10.1056/NEJMoa2309169