Ongoing Clinical Trials in Locally Advanced Cervical Cancer


Closing out their discussion on locally advanced cervical cancer, panelists discuss ongoing clinical trials and the potential of the involved novel therapies.


Bradley Monk, MD, FACOG, FACS: Here’s another trial that I run, trying to be faster, to utilize biology, taking the standard treatment of chemotherapy and radiation. To your point, Dr Tewari, it’s studying high-risk patients, patients who have stage IIIB or IIIC positive nodes, or even aortic nodes, and randomized them to chemotherapy, radiation, placebo versus durvalumab, added both in the radiation phase and in the maintenance phase for up to 24 months. That study is called CALLA, and that study is enrolled. If you go to in the public domain, it’s 714 patients, and it’s been closed since December 2020. Dr Thaker, does it have a chance?

Premal H. Thaker, MD, MS:I think it does.

Bradley Monk, MD, FACOG, FACS: Why?

Premal H. Thaker, MD, MS:It has a chance because we’re moving up therapies, moving more contemporary therapies up earlier. There is a huge chance for this to be more positive in terms of its outcome.

Bradley Monk, MD, FACOG, FACS: I hope so, but as I said, we’re not always right. It’s not my study, I read it on behalf of the world. You’re doing another study within the GOG [Gynecologic Oncology Group], Dr Pothuri, the KEYNOTE-A18 trial? Is that right?

Bhavana Pothuri, MD:Yes. The KEYNOTE-A18 trial is an ENGOT [European Network for Gynaecological Oncological Trial groups] and GOG partners collaboration. It’s a randomized phase 3 trial with chemoradiotherapy with or without pembrolizumab for high-risk locally advanced cervical cancer. And 980 patients are anticipated to receive pembrolizumab on day 1 of a 3-week cycle for 5 cycles, followed by pembrolizumab on day 1 of a 6-week cycle for 15 cycles. The dual primary outcome is both PFS [progression-free survival] and OS [overall survival]. Both of these studies are going to be important, and moving up checkpoint inhibitors earlier in the treatment paradigm is key because we can affect outcomes for patients even more.

Bradley Monk, MD, FACOG, FACS: Yes, I hope so for patients. There are 3 ways to make anti–PD-1 or PD-L1 better, and you just talked about one. The CALLA and KEYNOTE-A18 trials, radiation and chemotherapy, that’s one way. The second way is to add an anti-VEGF therapy. And third, another checkpoint inhibitor, which could either be a TIGIT [T-cell immunoreceptor with immunoglobulin and ITIM domain] or a CTLA-4. Drs Thaker, Pothuri, Huh, and Tewari, if CALLA and the KEYNOTE-A18 trials are positive, the next trial is to add either TIGIT/PD-1, PD-L1, or CTLA-4/PD-1, or add in a maintenance phase, an oral TKI [tyrosine kinase inhibitor]. Dr Tewari, remember we did a pazopanib study?

Krishnansu S. Tewari, MD:It’s not very well tolerated. I’d steer away from that.

Bradley Monk, MD, FACOG, FACS: OK. To your point, pembrolizumab/lenvatinib, that’s the VEGF/PD-1 in non–MSI [microsatellite instability]-high endometrial cancer. You all work on it. I want to be involved because I think we have more work to do.

Transcript edited for clarity.

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