Second-Line Treatment Options for Recurrent or Metastatic Cervical Cancer


A gynecologic oncologist discusses second-line treatment options for patients with recurrent or metastatic cervical cancer, and provides insights on toxicity management.

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.


  • 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.


Ritu Salani, MD: Unfortunately, it’s not uncommon for patients just like our case to have recurrence despite these advances in frontline therapy. Thinking about next-line therapy or second-line therapy is common and is based on a patient’s toxicity profile, the interval of disease-free treatment if they had one, and the patient’s goals. We’ve had some exciting advances in the recurrent setting, and I want to review a couple of these with you.

First is tisotumab vedotin, an antibody-drug conjugate [ADC] targeting tissue factor, which is widely expressed in cervical cancer. No testing is advised; therefore, no biomarker testing is required. Tisotumab vedotin can be used in patients regardless of whether they have PD-L1 expression or not. The reason why this is a preferred regimen in the second-line setting is we see response rates of about 24% in this patient population after frontline therapy, and this is compared with chemotherapy where we see about 6% to 7% response rates. [There is a] significant difference in objective response rates, and we also see an overall survival rate of about 12 months in this patient population. Patients may have other biomarkers that may not be FDA approved, but there may be clinical trial options available for these patients.

Recent exciting data were from patients with HER2 expression who received trastuzumab deruxtecan, which is the ADC targeting HER2 amplification or expression. [Results of] this study showed that patients had significant response rates with this regimen. This is not ready for prime time. It’s a small subset of patients, but very exciting data. Chemotherapy also continues to remain an option for treatment of patients who’ve progressed after receiving the frontline therapy, including pembrolizumab. If they did not receive pembrolizumab, perhaps prior to the approval, it is an option as second-line therapy in patients who have PD-L1 expression or CPS [combined positive score] greater than 1. However, it should be used in the frontline setting for these patients.

Tisotumab vedotin has an accelerated FDA approval for second-line therapy in the recurrent setting for patients with cervical cancer. Whenever we have a new therapy, we always have to deal with new toxicities. Tisotumab vedotin is well tolerated, but understanding the toxicities is really critical. Not uncommon to antibody-drug conjugates, we are seeing some new ocular toxicities, and tisotumab vedotin is no exception. In using this drug, it is important to know that patients must have an eye examination prior to every infusion. Partnering with an eye specialist, ophthalmologist, or optometrist is really important. Patients also have to use eye drops at the time of their infusion, as well as lubricating drops throughout their treatment course and for a little bit afterward. They also need to use cold packs during their infusion therapy to help reduce the development of keratitis. Making sure patients and infusion centers abide by the mitigation strategies to help reduce these toxicities is really important because we want to keep these patients on an effective therapy and minimize toxicities to therapy as much as we can. I always counsel my patients pretty aggressively in the beginning about the importance of adhering to the eye plan. It is very manageable, and patients tolerate it very well.

One of the other toxicities we see with tisotumab vedotin is peripheral neuropathy. This is something that we do see in patients, particularly if they’ve received paclitaxel beforehand, which may be compounded with tisotumab vedotin. We do tend to see a little bit more of proximal neuropathy. These patients may have difficulty washing their hair or getting up out of a chair when they’re using their arms. Therefore, asking the right questions is going to be really critical. When patients develop this toxicity, dose reduction or holding the dose can be really helpful in helping them overcome and reverse their toxicity to a grade 1 or grade 0 before rechallenging them with therapy. One of the other toxicities that’s notable is bleeding, and this can be, [for example,] nosebleed. Making sure that patients are using cold packs is helpful, and letting them know to monitor for bleeding can be really important.

Transcript edited for clarity.

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