Open Surgery Approaches and Sequencing Considerations Represent Core Parts of the Shifting Cervical Cancer Field

Sequencing challenges emerging represent an aspect of the changing cervical cancer landscape as new agents receive FDA approval and as investigators begin to evaluate whether pembrolizumab (Keytruda)/atezolizumab (Tecentriq) should be given in the metastatic setting for patients who previously received immune checkpoint inhibitor (ICI) therapy, according to Ritu Salani, MD, MBA.1

Notable changes in this space also include a turn towards an open approach and less radical surgery based on recent data. However, the phase 3 ROCC trial (NCT04831580) in patients with early-stage cervical cancer is using additional precautions and reexamining the role of minimally invasive surgery.1,2

“There are some exciting trials in the cervical cancer space that should be on everybody’s radar too, particularly with TROP2 antibody-drug conjugates, which are being looked at in the second line for patients after receipt of platinum-based chemotherapy with immunotherapy whether it’s with radiation or with chemotherapy,” Salani said. “Continuing to look at opportunities to improve the landscape is critical.”

In an interview with OncLive®, Salani detailed changes in the cervical cancer field, many of which were outlined in a review article she coauthored in Current Opinion in Obstetrics and Gynecology. She is a gynecologic oncologist and the director of the Division of Gynecologic Oncology at UCLA Health in Los Angeles, California.

OncLive: How has your practice changed as surgical practice has shifted towards an open approach and less radical surgery?

Salani: Due to recent surgical studies that have shown that an open approach [results in] less recurrence and less rates of death [vs] minimally invasive approaches for patients with early-stage cervical cancer, my practice changed to shift to open approaches for these patients. However, [the] ongoing [ROCC] trial is relooking at the role of minimally invasive surgery in early-stage cervical cancer with some additional precautions, including tumor containment systems as well as avoidance of using uterine manipulators. The study investigators are also ensuring that all the surgeons who are enrolling [patients] have experience in doing the prescribed protocol measures to ensure that the standard is being maintained. I’m very excited to see these study results, and maybe we’ll open the door for minimally invasive surgery with some additional measures to ensure we can do it safely for our patients.

Less radical surgery is a nice approach for patients who have early-stage disease and meet certain criteria where we can reduce morbidity from surgery. However, patient selection is very important and ensuring that we are not harming patients by doing less radical surgery in those who have not been fully evaluated or fully meet those selection criteria [is important].

Your review article highlighted that the role of pembrolizumab/atezolizumab in the metastatic/recurrent setting is the standard but may need to be reassessed in those who received prior ICI therapy. What data and considerations are important to note for your colleagues?

There have been 2 large studies that have looked at the role of checkpoint inhibitors in addition to chemotherapy for patients with metastatic or recurrent cervical cancer. Only the incorporation of pembrolizumab with chemotherapy with or without bevacizumab [Avastin] is FDA approved in the US—atezolizumab with bevacizumab and chemotherapy was also studied but is not on label in the US. But both studies [evaluating these regimens] showed a significant impact in both progression-free survival and overall survival. Incorporation of [them for] select patients is critical, and it should be the standard.

Since those studies have been conducted, we had the advent of immunotherapy being incorporated into chemoradiation for patients [whom] you may consider to have high-risk locally advanced cervical cancer. Therefore, some patients may already be experienced with checkpoint inhibitors by the time their cancer recurs. Understanding the role of ICI therapy after ICI therapy remains a needs gap for us because we have not encountered that yet. Whether we should use immunotherapy again, if it should be a different combination, or if we should avoid it is still something that’s unclear at this time.

As the second-line setting shifts with the new options of tisotumab vedotin-tftv (Tivdak) and fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) for select patients, how has sequencing changed?

Currently, tisotumab vedotin is the second-line therapy after patients have experienced recurrence on first-line platinum-based therapy with or without immunotherapy, and most patients will have received immunotherapy. HER2 is an exciting target, [and] it’s not highly prevalent in cervical cancer, so if you find it, it is a good target—we’re talking about [IHC] 2+ or 3+ expression. Both tisotumab vedotin and T-DXd could be used in a patient, and how you sequence them may be based on access, patient understanding, and the expression rates because very few patients will be candidates for HER2-[targeted therapies] with cervical cancer.

Sequencing continues to be an interesting challenge, and understanding which therapies may have the best response, but also the longest duration, is key. It makes good sense to use T-DXd in patients with HER2 3+ expression because we’re seeing provocative response rates and impressive durations of response [in this population and] it’s not typical to see that. [However,] tisotumab vedotin has an all-comers indication.

How does the December addition of neratinib (Nerlynx) as a second- or later-line treatment option to the NCCN guidelines for patients with recurrent or metastatic cervical cancer harboring a HER2 mutation change sequencing decisions?

[Investigators examining] the role of neratinib were looking at patients with somatic mutations, not HER2 IHC expression, so it’s still an option for these patients. It is a bit of a challenging drug to administer [and] there are some adverse effects that both patients and providers need to be ready for, particularly diarrhea, but it’s always good to have options for these patients. I’m not sure that using neratinib would preclude using T-DXd and vice versa. Checking for these mutations is becoming standard as we’re now using next-generation sequencing. If you find it, it’s good to keep [neratinib] in your arsenal of treatment regimens for patients.

References

1. Venkat PS, Smick AH, Salani R. Current opinions: updates on the changing landscape in the management of cervical cancer. Curr Opin Obstet Gynecol. 2025;37(1):16-21. doi:10.1097/GCO.0000000000000999
2. A trial of robotic versus open hysterectomy surgery in cervix cancer (ROCC). ClinicalTrials.gov. Updated December 19, 2024. Accessed February 12, 2025. https://clinicaltrials.gov/study/NCT04831580