Tisotumab Vedotin Shows Potential in Cervical Cancer With Disease Progression

3D illustration of female reproductive system: ©Crystal Light - stock.adobe.com

As the fourth most commonly occurring cancer in women and seventh most common overall,¹ cervical cancer has been the subject of much recent research to identify safe and effective treatments. One of those studies is the randomized, open-label, phase 3 innovaTV 301 (NCT04697628) trial of which data were presented at the European Society for Medical Oncology Congress 2023 in Madrid, Spain.

The innovaTV 301 trial compared tisotumab vedotin-tftv (Tivdak) with investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer with disease progression on or after treatment with standard of care chemotherapy and/or bevacizumab (Avastin) and/or anti-PD-(L)1 therapy.

Patients in the tisotumab vedotin arm experienced a 30% reduction in risk of death vs chemotherapy, a longer median overall survival of 11.5 months (95% CI, 9.8-14.9) vs 9.5 months (95% CI, 7.9-10.7)with chemotherapy (HR, 0.70, 95% CI, 0.54-0.89; P = .0038), and an overall response rate of 17.8% (95% CI, 13.3%-23.1%) vs 5.2% (95% CI, 2.8%-8.8%) was also tolerable. Tisotumab vedotin’s safety profile was also tolerable.

In an interview with Targeted Oncology^TM, Brian Slomovitz, MD, gynecologic oncologist, director of gynecologic oncology, Mount Sinai Medical Center, Miami Beach, Florida, and primary investigator of the innovaTV 301 trial, discussed recent data in the cervical cancer space and what the future of cervical cancer treatment looks like.

Brian Slomovitz, MD

Targeted Oncology: What is the current standard of care for recurrent or metastatic cervical cancer?

Slomovitz: Cervical cancer is a deadly disease, so it’s something that we need to do better at. Currently, the standard of care for cervical cancer starts off when it's spread. We have chemotherapy with an anti-angiogenic agent or bevacizumab.Recently, there were data that suggests we give it with pembrolizumab [Keytruda], an immunotherapy. In the second-line setting, the best that we've had has been chemotherapy.

By doing this trial, we came up with a treatment option that we didn't have for these patients, and something that's different from checkpoint inhibition, immunotherapy, and chemotherapy. It uses a technology called an antibody drug conjugate, an ADC, and it's novel in this disease.

What were you looking for in the innovaTV-301 trial? What were the findings?

In this study, the primary outcome was overall survival. The 2 treatment arms were the experimental drug tisotumab vedotin vs traditional chemotherapy, investigators’ choice chemotherapy. What we found here is that those women who were treated with the experimental drug had a 30% decreased risk of death vs those treated with the traditional therapy. We saw similar changes as well in the progression-free survival…[with a] 33% decrease in progression-free survival. We saw a response rate that was approximately 3 to 4 times higher in the tisotumab vedotin arm vs chemotherapy. [For] the safety profile, there were no new safety signals to make us concerned that something else was going to come up.

3D illustration of cervical cancer cell: ©PRB ARTS - stock.adobe.com

What are the implications of this research for cervical cancer?

In oncology care, we want to find the best treatment that treats all patients. But without doing that, we want to take positive steps. This is a tremendous step in the right direction to find a new cure. That increased overall survival is getting us to where we want to be. It's not that 1 study; it'll be a series of several studies that get us there. But to start off with a significant advantage, I think, is the right way to go as far as ADCs.

In general, we're really learning in the ovarian cancer [space]. We just had a phenomenal study showing mirvetuximab soravtansine [Elahere] does the same thing. It increases overall survival in patients who suffer from ovarian cancer. There was a paper presented at last year's ASCO meeting, something called DESTINY-PanTumor [NCT04482309] looking at an ADC against HER2. And those results were unprecedented. Based on those results, we're going to move forward and do additional trials with that type of target and other similar targets. ADCs are really the future for a more of a precision type [of treatment] to kill the cancer cells.

What are the next steps?

I think the next steps are going to be looking at combinations and moving into earlier-line settings. When we move into the earlier line, we want better results to help keep the disease away longer. Ultimately, in all cancer care, the word “cure” is something that we don't hear. But if we can get a way to cure some of our patients…if we move forward, we may have that opportunity. But we're seeing that with immunotherapy and in endometrial cancers, we're seeing the word “cure.” We saw that with PARP inhibitors and in BRCA-mutated ovarian cancers, where a percentage of patients are cured.

If we could get to a point with recurrent or metastatic cervical cancer, if we can get a portion of those patients cured, it'd be unprecedented. It's something that we've never even imagined. This is horrible, that not only is it a deadly disease, but also cervical cancer, as we know, affects some younger women, women with young kids, with young families, that and we really want to help make a difference. And iIt's important that we keep our feet on the gas and we keep pushing forward, because that's what we want to do for our patients: help them live forever.

REFERENCES:

1. Cervical cancer statistics. World Cancer Research Fund International. Updated March 23, 2022. Accessed October 25, 2023. https://tinyurl.com/3s4smvxt