Clinical Pearls and Future Directions of Cervical Cancer Treatment

EP: 1.Patient Profile: A 50-Year-Old Woman With Cervical Cancer

EP: 2.Cervical Cancer: Classification, Staging, and Prevention

EP: 3.Current Role of Biomarker Testing in Cervical Cancer

EP: 4.Metastatic Cervical Cancer: First-Line Treatment Options

EP: 5.Second-Line Treatment Options for Recurrent or Metastatic Cervical Cancer

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EP: 6.Clinical Pearls and Future Directions of Cervical Cancer Treatment

Case: A 50-Year-Old Woman With Cervical Cancer

Initial Presentation

• 50-year-old, black woman busy with family – teenage/college kids; FT work outside the home; now helping parents as mom is recovering from a knee replacement
• Last cervical cytology and HPV testing – 6 years ago; GYN doctor retired 2 years ago; not connected with new gynecologist.
• Complains of pelvic pain during intercourse, vaginal bleeding post-intercourse
• Pelvic MRI with contrast: involvement of lower vagina, pelvic sidewall, pelvic lymph node positive
• Neck/chest/abdomen/pelvis/groin FDG-PET/CT: liver metastasis
• Clinical Staging: Stage IVB
• IHC molecular testing results: PD-L1 positive, CPS >1
• Received pembrolizumab + cisplatin/paclitaxel + bevacizumab first line for 6 cycles; 6 additional cycles with pembrolizumab + bevacizumab. The patient had a complete response and opted to d/c maintenance treatment.

Follow-Up

• 11 months later the patient presented with complaint of cough.
• MRI: Metastatic nodules in right upper lung confirmed.

Treatment for Recurrence

• Tisotumab vedotin was initiated.

Transcript:

Ritu Salani, MD: Looking to the future for cervical cancer is really important. We’ve talked a little bit about the frontline therapy and second-line therapy options, but the story doesn’t end here. I think some exciting areas of exploration in cervical cancer include combination immune therapy.

There are studies looking at treatment options for patients who have received prior checkpoint inhibitor therapy with other combinations of immunotherapy, and this may include a checkpoint inhibitor with CTLA-4, TIGIT, and other bispecifics looking at PD-1 and other combinations. These studies are going to be informative and help us understand what the role of checkpoint inhibitor therapy after checkpoint inhibitor therapy is—if one exists. There are some other exciting areas that I think warrant discussion.

Using TIL [tumor-infiltrating lymphocyte] therapy has been recently explored, and we see response rates of about 44% in patients with recurrent cervical cancer. This is much higher than what we’ve historically seen, but we have to recognize that TIL therapy is really complicated. It’s very resource intensive and should be done in areas of excellence where they have TIL therapy programs. This treatment requires surgery to remove the patient’s tumor to create the TIL therapy, which is then later infused with a myelosuppressive agent. It does require a hospitalization, and we often partner with our bone marrow colleagues to administer this. TIL therapy is also being explored in melanomas. Partnering with our medical oncologists who [manage] melanomas is also critical because this therapy can be very challenging to administer, but in select patients it can really be a game changer. Not only are we seeing response rates unlike what we’ve seen before, we’re also seeing complete responses that are durable, lasting years in patients [whose disease] we once thought was incurable. I think this therapy definitely deserves further exploration.

When we think about future directions and [treatment] of current patients, it’s always important to think about how we sequence treatment. We know that the addition of pembrolizumab to the chemotherapy backbone in primary advanced or recurrent cervical cancer really has changed the game and should continue to be used in those patients who have CPS [combined positive score] greater than or equal to 1. The use of tisotumab vedotin has also advanced the care of these patients. We’re waiting for the confirmatory trial, but this is an option right now and should be utilized. Cervical cancer is a rare disease, and those who have advanced or recurrent disease are an even smaller subset group. If you see only a few cervical cancers a year, you may not be comfortable with using this treatment. Partnering with medical or gynecologic oncology colleagues is important for giving these patients therapy that has improved efficacy and manageable toxicities; it is really important so we can continue to provide these patients the best options for their treatment. Using immunotherapy after immunotherapy, I think, is yet to be understood, but there are clinical trials. Once again, either offering patients clinical trials or partnering with centers that have clinical trials may be important. I talked about some other biomarkers that are up and coming, including HER2 expression or HER2 gene amplification, but using NGS [next-generation sequencing] may also be informative for unique mutations where patients may be candidates for basket trials or phase 1 trials….

Now that we know that frontline therapy has been pretty well established, we need to continue to address the unmet needs in cervical cancer. Tisotumab vedotin is currently filling one of those need gaps, but understanding where the future of cervical cancer lies is really important. The use of pembrolizumab in the local advanced setting is being explored. Combining pembrolizumab with chemoradiation is being evaluated, and that study will hopefully read out within the next year. This may move immunotherapy even earlier in treatment, and we may actually create a new unmet need in cervical cancer. I think it’s really important to continue to explore options of treatment for these patients, including immunotherapy after immunotherapy, and then looking at novel combinations. We talked about immunotherapy combinations, but also looking at tisotumab vedotin with immunotherapy, tisotumab vedotin with bevacizumab, and other novel combinations, including the role of the trastuzumab, an ADC [antibody-drug conjugate], and what role that might play in patients who have HER2 expression with cervical cancer. It’s a small subset of patients, but those patients who have that positive biomarker may benefit from that therapy.

Transcript edited for clarity.