Emerging Opportunities for the Treatment of Cervical Cancer

At the 2022 Great Debates & Updates in Women’s Oncology virtual meeting, Ritu Salani, MD, University of California, Los Angeles,  discussed the changing landscape of treatment for cervical cancer.

In her presentation, Dr Salani discussed trials evaluating chemoradiation for locally advanced cervical cancer, immunotherapy combinations for advanced or recurrent disease, and the significant success seen with tisotumab vedotin for recurrent cervical cancer.

Transcript

Greetings. My name is Ritu Salani, I'm a gynecology oncologist at UCLA, where I'm Division Director and Professor of OB/Gyn. It's a pleasure to talk to you today about updates in cervical cancer, and there's been a lot of exciting new treatment options and ongoing studies in cervical cancer that have changed the landscape in treatment for women afflicted with this malignancy.

First, I'd like to start with locally advanced cervical cancer. We've unfortunately had a few negative studies or trials in the past year for patients receiving chemoradiation for stage 1B to stage 4A cervical cancer, and this includes 2 key trials. First, the OUTBACK trial, which looked at women receiving chemoradiation and brachytherapy, followed by adjuvant carboplatinum and paclitaxel. The thought was that this regimen would reduce the risk of recurrence, particularly distant recurrence. When the final analysis was presented last year, it did demonstrate that the addition of carboplatin and paclitaxel did not provide any benefit, and was potentially harmful with side effects of therapy, and this is no longer advised or being pursued.

Another trial also looked at chemoradiation in a similar population, but with the addition of immunotherapy, with durvalumab to chemoradiation with a maintenance strategy for 1 year. This study also just presented last week at the International Gynecologic Cancer Society meeting and it demonstrated no added benefit with the addition of durvalumab. There are some concerns with this trial, including that it may be a lower-risk population, so further studies are ongoing to explore the role of immunotherapy in this setting.

I think the most exciting topics were in the advanced cervical cancer setting. And this includes, last year, the addition of pembrolizumab to front-line chemotherapy with platinum, taxane, and with or without bevacizumab. This was able to demonstrate an overall and progression-free survival benefit in women who had a [combined positive score] CPS score greater than or equal to 1%. This was very exciting and has now become the standard treatment for women with advanced or recurrent cervical cancer, and just requires that biomarker expression for approval for the regimen.

The most exciting areas are in the recurrent setting and in combination studies where we continue to need therapies to treat these patients. We know that when cancer is recurrent or advanced, that our cure rates are extremely low, and this affects young women. Tisotumab vedotin is one of the newer agents that's on the market. It has accelerated FDA approval for women after front-line therapy in the recurrent setting. This demonstrated a response rate of about 24% with a median duration of response of about 8 months and an overall survival of about 12 months. Although this does not seem like a significant impact, it is when compared to standard chemotherapy, where historical controls are about 6% and median overall survival was about 6 months. It has made an impact and is now an option for recurrent cervical cancer therapy. It also seems to be well tolerated with appropriate mitigation strategies for new ocular toxicities that might be seen with this agent.

Additionally, tisotumab vedotin is being studied with in combination with immunotherapy, and now we'll need understand the true role of where immunotherapy is best applied for patients with recurrent cervical cancer, whether it's front-line or in the recurrent setting, and if rechallenging treatment with immunotherapy is favorable. The combination of tisotumab vedotin and pembrolizumab has some compelling response rates, at 38%. I think looking at this further in larger populations and determining which populations are best for this regimen is very exciting.

There are also other agents, including bispecific agent AKA104, looking at CTLA-4 and PD-1 inhibition, which has approval in China. This study had exciting response rates and has been further explored in other areas. I think there are a lot of exciting topics or new avenues for cervical cancer that are being explored, and I think this will continue to change the landscape for our patients.

Source

Salani, R. Emerging Opportunities for the Treatment of Cervical Cancer. Presented at: Great Debates & Updates in Women’s Oncology. Sep 21-23, 2022. Virtual.