Allegheny Health Network Oncology Experts Dive Into Updates Within the Gynecologic Oncology Space

Eirwen M. Miller, MD

In an interview with OncLive^®, Eirwen M. Miller, MD, a gynecologic oncologist at the Allegheny Health Network (AHN) West Penn Hospital, in Pittsburgh, Pennsylvania, discussed key points from her AHN colleagues’ presentations during an OncLive State of the Science Summit™ on gynecological cancers, which she chaired. Miller spotlighted updated data within the endometrial, cervical, and ovarian cancer spaces following the ESMO Congress 2023 and the 2023 ASCO Annual Meeting, focusing on how these updates continue to shift clinical practice and advance care.

She also explained the renewed focus in using PARP inhibitors, antibody drug-conjugates (ADCs), and the importance of emerging targets in ovarian cancer. Additionally, Miller provided further insights from a case study presentation that she and colleague, Christopher B. Morse, MD, gave on endometrial cancer in another interview.

OncLive: What were key takeaways from the presentation by Christopher B. Morse, MD, on tumor testing in endometrial cancer?

Miller: [There are] a variety of ways in which we’re looking at tumor testing and molecular profiling. With the revision of endometrial cancer staging, we’re seeing The Cancer Genome Atlas [TCGA] molecular subtypes come into clinical practice. Where historically we have not considered molecular subtype and staging, we’re now going to need to consider p53 status, POLE status, [and] mismatch repair–deficient status [which] has a huge role in treatment planning. We now have four TCGA subgroups that are worth considering and understanding from a prognostic standpoint.

[We] also [need to consider] a variety of molecular targets for our targeted therapeutic agents to understand what target options we have [for] patients when we’re developing their treatment algorithms. We have markers that are predictive, prognostic, and some of which are both. Overall, Dr Morse did a nice job highlighting those differences and how those molecular studies are going to become more critical in our treatment algorithms.

What key data from the ESMO Congress 2023 did Thomas C. Kirvak, MD, discuss in his presentation on updates in cervical cancer?

There was an exciting amount of data that was presented at the ESMO Congress [last] year and Dr Kirvak summarized an astronomical amount of data [that came out] in a very short period of time. The data that we saw at ESMO is probably going to start to change our practice. He presented the results of the phase 3 NRG-GY018 study [NCT03914612] looking at incorporation of pembrolizumab [Keytruda] with chemoradiation followed by pembrolizumab as a maintenance strategy in locally advanced cervical cancers. That study met its primary end point of progression-free survival benefit. I am already looking to incorporate immunotherapy into my treatment algorithms for those patients.

Dr Kirvak presented the data from the phase 3 INTERLACE study [NCT01566240] which evaluated a strategy of weekly paclitaxel and carboplatin for 6 cycles prior to chemoradiation for locally advanced cervical cancers. That study also showed a survival benefit. We’re seeing that in a group of high-risk patients who have high recurrence rates after completion of chemoradiation that adding either chemotherapy before or immunotherapy in combination with chemoradiation improves the survival of patients with this high-risk disease. I don’t think any of us know yet exactly how those studies are going to interplay with one another when we design treatment algorithms for patients, but it is exciting to see studies that are moving the needle forward for a group of patients that historically have not done well [which includes] patients who have high risk of recurrence with not [a lot of] robust treatment options afterwards.

Dr Kirvak also presented the overall survival [OS] data [from the phase 3 innovaTV 301 trial NCT04697628] evaluating tisotumab vedotin-tftv [Tivdak], which is an exciting drug that we’ve had available to us in gynecologic oncology for a couple of years, in recurrent cervical cancer. The OS results support the use in clinical practice and supports the approvals that we have. Certainly, having more options in a disease space where we’ve had limited options and with a drug that is tolerable for patients is exciting.

John Nakayama, MD, discussed navigating PARP inhibitors for ovarian cancer. What notable advancements within this landscape were highlighted?

We dissected the “Dear Health Care Provider” letters that were released with the FDA indication withdrawals of all of our PARP inhibitors in the platinum-sensitive setting as a maintenance therapy, [aside from for] patients who have a BRCA mutation. Where we used to have an FDA indication for rucaparib [Rubraca], olaparib [Lynparza], and niraparib [Zejula] for all comers that had a complete or partial response to platinum-based chemotherapy in the platinum-sensitive setting, that indication is now limited to patients with a BRCA mutation.

Dr. Nakayama’s presentation was targeted as an educational opportunity and an opportunity to talk about how we use PARP inhibitors in the first-line. As a group when we talk about this, we all feel strongly that patients see a PARP inhibitor at some point during their therapy. My personal take is that I’m more apt to give a patient a PARP inhibitor in the frontline setting now, understanding that may be their only opportunity to see a PARP inhibitor during their care. We don’t have a lot of updates in the last 6 months about these PARP inhibitor trials, but there are some changes in practice because of these “Dear Healthcare Provider Letters”.

What was noted regarding ADCs and emerging targets in ovarian cancer as discussed by Sarah Crafton, MD?

We had the initial results of the phase 3 MIRASOL trial [NCT04209855], which evaluated the role of mirvetuximab soravtansine-gynx (Elahere) in platinum-resistant ovarian cancer, presented to us at the 2023 ASCO Annual Meeting [last] summer. There was an OS benefit with mirvetuximab soravtansine when compared with investigator-choice chemotherapy.

This is an incredible option for our patients in an unmet need area—I particularly like the toxicity profile of this medication. A lot of these patients are heavily pretreated and have had significant hematologic toxicities related to prior cytotoxic chemotherapy, and there tend to be very tolerable hematologic toxicities with this medication. In terms of the ocular toxicities associated with [the agent], the more we use it, the more comfortable we’re becoming with it; we’re also developing strong algorithms for referrals to ophthalmology, strong relationships with the eye care professionals for frequent eye exam screening, and are being proactive educating patients about the symptoms of ocular toxicity.

This is an exciting medication as it’s hard to show OS benefit in platinum-resistant ovarian cancer. Mirvetuximab soravtansine is going to change practice and is already changing practice.

Dr Crafton also highlighted the ADCs that are currently under investigation in clinical trials and many of the ADC targets are FRα, but there are also some agents targeting TROP-2. [There are a few] clinical trials that are currently open to enrollment or will soon be open, and it’s important that we enroll patients onto [these trials] to advance this field forward.

What would be your main message for colleagues in the gynecologic oncology space?

The main message is that our field is changing so rapidly. What we thought we knew about endometrial cancer, ovarian cancer, and cervical cancer [has changed]. We’ve seen practice changing data in each of these disease spaces presented to us in the last 12 months, and we need to openly be communicating with one another about how this data changes our practice and how we can continue to provide state of the art care to our patients. Education is the only way these studies are going to make their way into clinical practice as we talk about them and educate one another, not shying away from new treatment regimens.

Is there any ongoing research your institution is involved in you would like to highlight?

Our division here at AHN is actively involved in clinical trial research. We have a variety of trials open in the endometrial cancer space as well as in in the ovarian cancer space, and most of these trials are targeted therapies. Now, we’re looking at patients whose tumors express FRα, TROP-2, and in endometrial cancer we’re looking at p53 wild-type disease.

To Dr Morse’s presentation of looking at molecular targets in endometrial cancer, that’s the direction that our field is going but beyond endometrial cancer—[we’re looking at molecular targets] in the ovarian cancer space and to some degree the cervical cancer space as well.

We’re proud to have a robust trial portfolio at AHN and are proud to offer this to patients as we truly believe that clinical trials are the first line standard of care that we should be offering to patients when they’re eligible. We are motivated to continue to contribute to the science.