Recent Advances in Cervical Cancer Treatment - Episode 10

Unmet Needs in Second-Line Therapy for Metastatic Cervical Cancer

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Switching its focus to second-line therapy for metastatic cervical cancer, the panel reviews an unmet need of effective therapy in this setting.


Bradley Monk, MD, FACOG, FACS: Dr Huh, please explain the standard of care for second-line cervical cancer. You discussed the historical standard of care in the first line and how it changed to BEV [bevacizumab], and now KEYNOTE-826 with PEMBRO [pembrolizumab] with or without BEV. What is the standard of care in the second line?

Warner K. Huh, MD, FACOG, FACS: It’s wide open. We have [pembrolizumab] for patients who are PD-L1 positive or MSI [microsatellite instability] high, and a litany of drugs that have been studied through the GOG [Gynecologic Oncology Group]. They include gemcitabine, mitomycin, and nab-paclitaxel, it’s a dealer’s choice. The response rates and survival related to these drugs are fairly minimal, which is why we’re interested in filling this gap. It’s an unmet need, so we try to put patients on clinical trials as much as we can. A lot of people in the United States are doing PD-L1 testing much earlier than they did 1 or 2 years ago, but it’s wide open. This is an area of great need.

Bradley Monk, MD, FACOG, FACS: Dr Tewari, we’ll discuss your study, EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9, which was a checkpoint inhibitor versus chemotherapy. Tell us about the chemotherapy performance in that study. How well does physician’s choice chemotherapy work in the second line?

Krishnansu S. Tewari, MD:Around 0% to 10% response.

Bradley Monk, MD, FACOG, FACS: Dr Tewari says 0% to 10% because there are things like topotecan, which is a single agent, and is inactive.

Krishnansu S. Tewari, MD:Yes.

Bradley Monk, MD, FACOG, FACS: We also have gemcitabine and vinorelbine. Dr Tewari, what’s your go-to regimen outside of a clinical trial and [pembrolizumab] for chemotherapy in this setting?

Krishnansu S. Tewari, MD:I learned a lot from you, but it depends on the histology. Since I don’t have an active agent, if I have a patient with an adenocarcinoma, I may treat them with pemetrexed. If they have a squamous lesion, gemcitabine is an option. Like Dr Huh said, the space is wide open because nothing works. We’ve been putting these patients on trials. The space has blown up with trials, so fortunately most of our patients in need of second-line therapy in the last few years were able to secure a place on a study.

Bradley Monk, MD, FACOG, FACS: Dr Huh, what’s your go-to agent for second line beyond checkpoint, biomarker negative?

Warner K. Huh, MD, FACOG, FACS:Second line beyond checkpoint?

Bradley Monk, MD, FACOG, FACS: Yes.

Warner K. Huh, MD, FACOG, FACS:Weekly Taxol [paclitaxel]. When you have a recurring patient and they’re PD-L1 negative, we know that patient is not going to do well. We don’t talk about it, but best supportive care must be brought into that discussion. It’s a tough choice, and we know that the outcome is going to be poor going forward.

Bradley Monk, MD, FACOG, FACS: Even pembrolizumab has a 14.3% response rate. It’s true, there is some stable disease, if you are lucky enough to see a responding patient, it’s durable. Dr Thaker, what’s your go-to regimen in the second line?

Premal H. Thaker, MD, MS:It’s like everyone else. Topotecan is not very useful, and the quality of life on that drug is tough when you get to this point.

Bradley Monk, MD, FACOG, FACS: My resident, Zach Alholm, [MD,] did a real-world analysis at US Oncology Network through a sophisticated electronic medical record analysis. In US Oncology, 11% of the market, this is after the approval of pembrolizumab, the rank and file were discouraged with checkpoint inhibitors. You all say you like checkpoint, but the practicing medical oncologist says 14% response rate. People go back to paclitaxel, to carboplatin, even bevacizumab after bevacizumab. As you said Dr Huh, you can give weekly paclitaxel/bevacizumab, but that was not possible in these clinical trials. Dr Pothuri, what’s your perspective on the best treatment? There are no good treatments, but we have to make decisions. How do you make the decision on what to use?

Bhavana Pothuri, MD:I think that’s untrue, as of 2 weeks ago, we have TV [tisotumab vedotin] now, we have a good option. I just told a patient I’m going to give it to her. The approval of [tisotumab vedotin] is exciting and we now have that as an option. The response rate is unheard of compared to these other agents that we’ve discussed. Beyond that, I agree with you, it’s the same weekly Taxol, or I use gemcitabine. I have that goals-of-care discussion when I’m starting that regimen. I even say, “I may not be helping you with this chemotherapy, and I may actually be harming you in terms of your quality of life, so let’s work together to figure out what the best next step for you is.”

Bradley Monk, MD, FACOG, FACS: I told my first patient yesterday—whom I did a biopsy on Thursday before September 20th when tisotumab vedotin was approved—and she began crying. She came to get her biopsy result, I told her its cancer, it’s a dermal metastasis and can’t be excised. I told her that since I did the biopsy, there’s a new medication, and she started to sob. This is an opportunity. The response rate is 24% with tisotumab vedotin, based on our GOG study, so it’s an option.

Transcript edited for clarity.