Metastatic Cervical Cancer: First-Line Treatment Options

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

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

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

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: As our case showed, the patient had stage IVB advanced cervical cancer and was PD-L1 positive. We know this can impact frontline data. Before I talk about her specific case and why we selected the regimen for her, I want to review a little background data. GOG 240 was a trial published in 2014. It showed that the addition of bevacizumab to chemotherapy had a progression-free survival and overall survival impact, and this became the standard of care at that time. There are some risk factors or adverse effect profiles that you may want to be aware of, particularly fistula formation, which can have a significant impact on the patient’s quality of life and outcomes. But it’s generally a very safe regimen to give to these patients, and it’s still the standard of care for patients who are PD-L1 expression negative or who have a CPS [combined positive score] of less than 1.

However, in 2021 we saw a study called KEYNOTE-826, which looked at that backbone of chemotherapy plus or minus bevacizumab with the addition of pembrolizumab. This was used in patients for all comers, but about 90% of patients were PD-L1 expression positive or had a CPS greater than or equal to 1. In this study, patients who received pembrolizumab compared with placebo had a significant impact in progression-free survival as well as overall survival. We also saw that these patients did well with this therapy. We did not see any new safety profile or toxicity concerns. This became the standard of care for patients who had PD-L1 expression or CPS greater than 1, as we see in our case. The combination of platinum, taxane, with or without bevacizumab, and pembrolizumab is a standard of care for patients with metastatic advanced cervical cancer, like this case, who has a PD-L1 expression noted in her cervical cancer tumor.

One of the biggest advantages of immune checkpoint inhibitor use for metastatic cervical cancer is the impact on progression-free survival and overall survival. At the ASCO [American Society of Clinical Oncology] Annual Meeting this year, we saw the final overall survival results of the KEYNOTE-826 trial, which incorporates pembrolizumab with that chemotherapy backbone. One of the interesting things noted was that about 40% of patients have prolonged favorable outcomes with the addition of pembrolizumab. Pembrolizumab can also be used in the recurrent setting. However, pushing it to the up-front setting seems to have a significant impact. Patients are having complete responses, and we may be seeing cures in patients that we hadn’t seen before. Reserving it for second line is not advised, and these updated data emphasize the importance of incorporating it with frontline therapy.

Transcript edited for clarity.