Immunotherapy Shakes Up Cervical Cancer Treatment Paradigm

The FDA approvals of pembrolizumab (Keytruda) and tisotumab vedotin-tftv (Tivdak) have brought much needed options to patients with metastatic or recurrent cervical cancer, respectively, explained Yovanni Casablanca, MD, who added that PD-L1 is now a must-test biomarker.

“When you have recurrent or metastatic cervical cancer that’s not amenable to surgery or localized treatment with radiation, PD-L1 testing with the assessment of the combined positive score is important to get as soon as you can, so that you can decide on the appropriate first-line treatment regimen. Chemotherapy is not going away, and the use of bevacizumab [Avastin] is not going away, but [PD-L1 testing] will help you decide if you want to add pembrolizumab to that backbone,” Casablanca said.

In an interview with OncLive^®, Casablanca, a Colonel in the Air Force and program director of the Fellowship in Gynecologic Oncology at the National Capital Consortium, Associate Professor, Department of Gynecologic Surgery and Obstetrics at the Uniformed Services University, discussed the incorporation of new treatments into the cervical cancer paradigm and provided insight into the necessity of inclusive research with novel therapies.

OncLive^®: You discussed the incorporation of new cervical cancer drugs into your practice at the SGO 2022 Winter Meeting. What pivotal approvals have affected your practice for women with cervical cancer?

Casablanca: Since the last SGO Winter Meeting that we had 2 years ago, there have been some breakthrough approvals from the FDA for use of new systemic treatment regimens in metastatic or recurrent cancer. One of those approvals is the addition of pembrolizumab to chemotherapy and bevacizumab in the first-line setting for cervical cancer based on data from the KEYNOTE-826 trial [NCT03635567].

After first-line treatment, there are a lot of promising options in the second-line setting. We have other immune therapies that, hopefully, will be approved soon, possibly, without the need for PD-L1 positivity, although we’ll see what the FDA decides. The other breakthrough was the approval of a new novel drug called tisotumab vedotin, which is an antibody-drug conjugate that is now approved in the second-line setting. The agent had remarkable duration of response, immediacy of the response, and overall survival [in the pivotal trial]. Compared with where we were 2 years ago, that’s a big improvement. Despite the challenges of the pandemic, there have been some breakthroughs and progress in the treatment of patients with metastatic and recurrent cervical cancer.

One of the things that was on community members mind, particularly with tisotumab vedotin is that this class of medicine is associated with ocular adverse effects [AEs]. There is a need for partnership with an eye care professional such as an optometrist or an ophthalmologist with knowledge of these AEs when you use this drug in the second-line setting, which is not a very common relationship. We don’t usually have our offices next door to an eye care professional. A lot of folks are not sure how they’re going to navigate and establish those relationships, but I discussed why it’s important to do so. There is an FDA blackbox warning about the ocular AEs. Thankfully, we have a mitigation and management plan for these ocular eye AEs. Proactiveness and educating the patient on the importance of their eye care plan will help to make this, hopefully, not as big of an issue.

What has been the biggest change in practice with the approval of pembrolizumab in the first-line setting?

For patients with metastatic and recurrent cervical cancer, the standard had been to utilize 2 chemotherapies and consider adding bevacizumab to it. That 3-drug regimen had been our standard 2 years ago. Now with the data from KEYNOTE-826, for patients who have PD-L1–positive tumors, we can add pembrolizumab to that regimen. The biggest change for clinicians is wrapping their head around using four drugs at the same time, potentially, to treat patients with metastatic or recurrent cervical cancer and getting PD-L1 biomarker testing as soon as this diagnosis is made, so that they can choose whether they’re going to add pembrolizumab [to that standard 3-drug regimen].

What are some of the disease-specific challenges of developing novel therapies for patients with cervical cancer?

Cervical cancer is a unique disease and patient population for us compared with endometrial and ovarian cancer. Metastatic and recurrent cervical cancer is not as common in our practice. [Cervical cancer] is not a very common disease overall, so that’s one challenge. One of the unique things about patients with cervical cancer is that they’re quite young overall. [Women with cervical cancer] are very young, otherwise healthy women, sometimes with families and children. It’s an important population, even though it’s a smaller population to focus on. The other thing that is important to highlight is that cervical cancer and advanced cervical cancer is a disease that is even a bigger burden and problem worldwide in underdeveloped countries or countries where preventive care is less robust. A lot of the breakthroughs that we have in the United States may not be as applicable globally. It really is a very niche type of research that’s done with these advancements, because it’s a smaller population with needs that vary from country to country. The population is very heterogenous too, even in the United States.

What therapeutic class has the most potential to make an impact on the paradigm?

With immune therapy and immunotherapy combinations—not just pembrolizumab-based combinations, but other immune therapy combinations, and novel immune therapy agents, such as TIL [tumor infiltrating lymphocyte] treatment—there is a growing amount of knowledge in the role of the immune system and the potential hope we have in immune therapy, not just as single agents, but in combination with standard regimens. I don’t think that the future of cervical cancer is going to hang on giving one drug at a time. I think the future of cervical cancer treatment is going to be using combinations of multiple treatments to see improvement in survival.

What can be done to make sure that these developments reach the community at large?

There are significant disparities in our country’s health care system. Cervical cancer patients have a vast demographic makeup with many cultural and racial ethnic backgrounds. By allowing and supporting clinical trial enrollment for every person and every population, we hope to improve the extension of these novel therapies to populations or subsets that normally wouldn’t have had access to them. There certainly is a lot of work to do to reach out to patients that are under or noninsured and patients that don’t have the access to larger or tertiary medical centers with novel therapies available.

Is there any research you’re involved in that you’d like to highlight?

So much activity is going on now in cervical cancer trials across the country, including the addition of immune therapy to the chemoradiation backbone for locally advanced disease and looking at combinations of therapies. Now that patients are getting immune therapy in the first-line setting: What do we do with immune therapy if they progress and need something in the second-line setting? Should patients get immune therapy again? Should we switch classes? How do we make immune therapy effective and tolerable at the same time? The trial that I’m involved in in the cervical cancer field is looking at adding triapine, which is a novel drug, to the backbone of chemotherapy and radiation in locally advanced cervical cancer.