Novel Immune Checkpoint Inhibitors in Advanced Cervix Cancer - Episode 2

Role of Anti–PD-1 and Anti-CTLA4 Agents in Cervical Cancer

An expert gynecologic oncologist discusses the rationale for using PD-L1 inhibitors and CTLA4 inhibitors in gynecologic cancers.

David M. O’Malley, MD: The percentage of patients who are going to relapse after primary therapy depends on the risk factors. Patients who have high periaortic lymph node involvement and locoregional disease are at much higher risk of relapsing, exceeding probably 40%. Those who present with advanced metastatic disease are essentially at 100% risk of relapse. For patients who have previously received or who haven’t received a previous immunotherapy, when they have the opportunity, I’m going to utilize an immunotherapy for the recurrent or second-line setting. If a patient hadn’t previously received a platinum doublet to include carboplatin or cisplatin plus paclitaxel with or without bevacizumab, that would be my first choice. Typically, most locoregional cancers will recur in the first 2 to 3 years.

We recently published the single-arm balstilimab trial on patients with recurrent persistent or metastatic cervical cancer. In that publication in Gynecologic Oncology, the PD-L1 inhibitor balstilimab showed an overall response rate of 15%, and the PD-L1–positive population response rate was 20%. But interestingly, in the PD-L1–negative population, we saw an 8% response rate. Clearly, this activity is similar to pembrolizumab and cemiplimab. At this point, though, balstilimab isn’t pursuing an accelerated approval in advanced recurrent cervical cancer, but it continues to be an option in combining with zalifrelimab.

The rationale for combining PD-1 inhibitors and CTLA4 inhibitors in cervical cancer speaks to the importance of potentially these synergistic—maybe synergistic is overstated—these 2 separate mechanisms of action. We’re removing the blockers of the immune response with the PD-1 inhibitors, and then we’re getting those tired T lymphocytes with the CTLA4 and we’re bringing more T lymphocytes into the immune response. The combination of PD-1 inhibitors and CTLA4 inhibitors and this dual blockade makes much more sense to give us the best opportunity for 1 overall response, and most important, sustained and durable responses with a dual blockade.

Transcript Edited for Clarity