Novel Immune Checkpoint Inhibitors in Advanced Cervix Cancer - Episode 1

Systemic Treatment of Metastatic/Recurrent Cervical Cancer

David M. O’Malley, MD, provides insight on the evolution of cervical cancer and reviews current systemic treatment options for recurrent and advanced disease.

David M. O’Malley, MD: The cervical cancer landscape has drastically changed over the last decade or 2. We now have vaccinations. Like any vaccination, it’s not perfect, but we need to start thinking about it as a cancer prevention shot rather than a vaccination. What about our treatment of recurrent cervical cancer? We still have about 14,000 cases in the United States, and over 4000 women die each year. Yes, cervical cancer is a worldwide problem, but it’s not just a worldwide problem. It’s still a problem in the United States.

Not that long ago, we were talking about an overall survival of 7 to 9 months with recurrent or advanced cervical cancer. We’ve moved from platinum-based therapy or other alkylating agents, showing that the backbone is platinum plus a taxane. GOG-0240 showed us the efficacy of antivascular therapy with bevacizumab, which is now getting close to an overall survival of 2 years. KEYNOTE-826 has shown that we may be curing women with recurrent and advanced cervical cancer with the utilization of immunotherapy. In less than 10 years, we’ve gone from less than a year to live to potentially curative intent.

The systemic treatment options for recurrent and advanced cervical cancer focus around the backbone of platinum and paclitaxel. We know over time that these are the 2 best cytotoxic agents. GOG-0240 showed us the advantage of antivascular therapy with patients who have advanced cervical cancer. Most recently, we’ve seen the advantage of the utilization of immunotherapy in patients with advanced recurrent cancer. We also need to consider those with locally advanced or locoregional disease. Clearly, the backbone is radiation plus cisplatin therapy. But multiple ongoing trials are looking at the utilization of immunotherapy in addition to these, remembering that most patients with recurrent cervical cancer—approximately 85%—will have had locoregional disease to start with.

What factors do I consider while looking at a patient with recurrent and advanced cervical cancer? Obviously, their performance status. But if we have a young patient, even with a compromised performance status, we’re going to continue to be aggressive with cytotoxic therapy. With antivascular bevacizumab being the best therapy and showing survival advantage, I’m going to utilize bevacizumab unless there’s a strong contraindication, like uncontrolled hypertension, which you should be able to control, or recent DVT [deep vein thrombosis]. Even in that situation, if those patients are anticoagulated, I’ll use bevacizumab. It does somewhat come with a risk of increased fistulization rate, particularly for patients who have had prior chemotherapy-radiation and have a centralized recurrence. It’s important to discuss this with the patients so they understand the risk, knowing that they may have a higher risk of fistulization. But when I talk to them about the survival advantage, most patients are going to utilize bevacizumab.

For indication, we’ll talk more about KEYNOTE-826. But it’s important that utilization of pembrolizumab in the up-front setting has shown additive response rates exceeding 70%. In addition, we’re seeing patients with overall survival advantage with the utilization of pembrolizumab. Even though this wasn’t a preplanned analysis of patients who are PD-L1–negative, the FDA elected not to approve it for those who are PD-L1–negative, defined as CPS [combined positive score] less than 1%. So patients who are PD-L1–negative won’t have the opportunity to utilize pembrolizumab in the up-front setting.

Transcript Edited for Clarity