Revolutionizing Frontline Cervical Cancer Treatment: Trials to Transformative Therapies

EP: 1.Navigating Complex Cervical Cancer Cases: Therapeutic Challenges and Innovations

EP: 2.HPV and Cervical Cancer: Prevention and Screening Strategies

EP: 3.Biomarkers in Cervical Cancer: Guiding Innovative Treatments

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EP: 4.Revolutionizing Frontline Cervical Cancer Treatment: Trials to Transformative Therapies

EP: 5.Recurrent Cervical Cancer Treatment Evolution: Immunotherapy and Beyond

EP: 6.Tisotumab Vedotin: Advancing Cervical Cancer Treatment

EP: 7.Managing Treatment-Related Side Effects of Tisotumab Vedotin

EP: 8.Innovations in Cervical Cancer Treatment: Exploring Tisotumab Vedotin Combinations

Transcript:

Ramez N. Eskander, MD: There has been a significant improvement in clinical outcomes based on our identification of effective systemic therapy in the [patient with] newly diagnosed metastatic cervical cancer or in the [patient with] recurrent treatment-naïve cervical cancer. And that evolution has been a result of many clinical trials. We had firstly, GOG [Gynecologic Oncology Group] protocol 204, which was a trial that looked at a cisplatin-based chemotherapy doublet. And from that trial, cisplatin and paclitaxel emerged as a preferred chemotherapy combination. That was published by Dr Monk and colleagues in JCO [Journal of Clinical Oncology] in 2018. Following that, we had the second subsequent trial to inform treatment, and that was GOG protocol 240, which was led by Dr Tewari.

GOG protocol 240 was a 4-arm trial, and it looked to determine whether there was going to be a benefit with the addition of bevacizumab to the chemotherapy backbone. Why? Because angiogenesis was a hallmark of cervical carcinoma, and that was discovered based on prior translational research and investigation, but also based on phase 2 studies showing efficacy of bevacizumab as a monotherapy. GOG 240 also wanted to [answer] the question [of whether] a nonplatinum doublet could improve outcomes. So it was a 2-by-2 factorial design: chemotherapy with or without bevacizumab. And then for the chemotherapy backbone, it was a platinum-based doublet or topotecan paclitaxel, which was a nonplatinum component.

And what we saw from GOG 240 was a significant improvement in the median overall survival with the addition of bevacizumab to chemotherapy. It went from 13.3 months to 17 months. That’s a dramatic improvement, and the median progression-free survival went from 5.9 months to 8.2 months. We had a significant improvement in progression-free survival and a significant improvement in overall survival with the addition of bevacizumab to chemotherapy. The nonplatinum doublet combination did not inform a change in practice. So GOG 240 established chemotherapy, cisplatin or carboplatin, plus paclitaxel plus bevacizumab as our treatment backbone for patients with metastatic or advanced-stage cervical carcinoma.

And then we evolved to … an era of immunotherapy. Why? Because we knew from the KEYNOTE-158 trial that patients who have cervical carcinoma [and] are PD-L1 positive by a combined positive score [CPS] responded to pembrolizumab. And if they responded, the median duration of response was not reached. So, of course, it became a rational next step to determine whether using pembrolizumab in these patients could improve clinical outcomes. So that was KEYNOTE-826. It was a phase 3 trial that looked at chemotherapy with pembrolizumab and pembrolizumab maintenance or chemotherapy placebo [and] placebo maintenance. And bevacizumab was at the physician’s discretion. That’s key because KEYNOTE-826 was not a trial that was designed to ask or answer a question about bevacizumab plus immunotherapy, but rather, it was really focused on the benefit of pembrolizumab, with bevacizumab being physician’s choice.

And because of that, it was a stratification factor. You had to know whether you’re going to give [bevacizumab] and whether you plan to use it. And thankfully, as was initially published by Dr Nicoletta Colombo, but of course updated by Dr Brad Monk at ASCO [American Society of Clinical Oncology Annual Meeting] in 2023, KEYNOTE-826 met its primary end points with a significant improvement in progression-free survival and overall survival in these patient populations. But an important caveat to that is that they looked at various CPS categories: PD-L1 CPS of 0, 1 to 10, and greater than 10. In the intent-to-treat population, it was positive in the 1 or greater population [and] it was positive in the greater than 10 population.…

So we saw a benefit across the board. Importantly, nearly 90% of patients were PD-L1 CPS 1 or greater; it was the vast majority of those enrolled. And that’s very important as we look to connect this to the clinical patients we care for…. If you look at the intent-to-treat population, the median overall survival was greater than 24 months, really dramatically changing how we treat these [patients with] advanced-stage cervical cancer. [It’s about] bringing this combination of platinum, paclitaxel, [and] pembrolizumab with or without bevacizumab as the preferred systemic chemotherapy strategy for [a patient with] metastatic or recurrent cervical cancer who is treatment naïve, who has a CPS in PD-L1 of 1 or greater. If they have a CPS of 0, then that doesn’t fall within the label. And those patients, of course, would have the GOG 240 [regimen] of platinum, paclitaxel, bevacizumab, and bevacizumab maintenance.

…We’ve seen overall survival transform. And why? As I mentioned earlier, in GOG 204, the median overall survival was [approximately] 12 months. GOG 240 took median overall survival for these patients to 17 months. And then KEYNOTE-826 took that to almost 26 months. So you’re seeing this really dramatic improvement in overall survival for patients who had a very guarded prognosis a decade ago. It’s dramatic, it’s exciting, and, most importantly, it gives our patients options.

Transcript is AI generated and edited for readability.