Treatment Considerations for Advanced or Recurrent Cervical Cancer: Q&A With Krishnansu S. Tewari, MD

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AJMC®: During the COVID-19 pandemic, rates of screening and routine cervical cytology screenings (Papanicolaou tests) considerably declined, particularly in rural areas and among certain racial and socioeconomic groups with low screening rates and limited access to screening. How do you think these trends will affect cervical cancer incidence and mortality? How could these risks be mitigated?

KRISHNANSU S TEWARI, MD: Although we have not formally studied this, it seemed as though during the COVID-19 pandemic, patients presented with more advanced disease, because (for the most part) many were quarantining and only came to the hospital after their cancer progressed enough to cause concerning symptoms.

AJMC®: How do you assess whether a patient’s newly diagnosed cervical cancer has the potential to become advanced or recurrent?

TEWARI: Staging according to the International Federation of Gynecology and Obstetrics (FIGO) is critical in order to determine the extent of the cancer at the time of diagnosis and the prognosis. Patients with stage III or higher cervical cancer, particularly those patients with metastases to the para-aortic nodes and lungs, have a high risk of disease recurrence.

AJMC®: At the time of diagnosis for advanced or cervical cancer, what treatment options do you consider? What factors into your decision?

TEWARI: The FIGO stage is important. Typically, early stage through FIGO stage IB2 cancers can be treated surgically via radical hysterectomy with bilateral salpingectomy and bilateral pelvic lymph node dissection. Locally advanced cancers (stage IB3 through IVA) are treated with chemoradiation and high dose-rate intracavitary brachytherapy. Patients who present with metastatic disease at diagnosis (ie, FIGO stage IVB) are treated with platinum-based combination chemotherapy plus the antiangiogenic drug bevacizumab. The patient’s performance status is also taken into account when considering therapeutic options.

AJMC®: In the EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 (NCT03257267) clinical trial of cemiplimab, patients with recurring or metastatic cervical cancer were enrolled regardless of PD-L1 expression. What was the rationale behind that decision, and were the results affected?

TEWARI: PD-L1 is a rather blunt instrument to guide therapy, because we know that checkpoint inhibitors have demonstrable activity in both PD-L1–positive and PD-L1–negative tumors. In addition, samples from biopsies of many patients with recurrent disease are very small; therefore, the levels of PD-L1 expression within the samples are not always discernable. In order to assess the activity of cemiplimab in a real-world population, we wanted to enroll patients in the trial regardless of PD-L1 expression. If we only had enrolled PD-L1–positive patients, we may have missed the opportunity to observe activity in the PD-L1–negative subpopulation.

AJMC®: Which targeted or systemic agents could be effective with cemiplimab as part of combination regimens?

TEWARI: This is an excellent question. Currently, there is a trial [NCT04646005] that is evaulating the combination of cemiplimab with [ISA101b], a human papillomavirus vaccine. Cemiplimab could be also combined with chemotherapy with or without bevacizumab, although that has not yet been studied.

AJMC®: Given recent advances in the treatment of cervical cancer, in what ways do you think treatment approaches and strategies are likely to change in the future? What are your key takeaways when it comes to optimizing patient care?

TEWARI: We have made steady progress to improve median overall survival in the first-line treatment of recurrent or metastatic disease, first with the addition of bevacizumab to chemotherapy doublets, and now with the addition of pembrolizumab to chemotherapy with or without bevacizumab. In the second-line setting, cemiplimab monotherapy has shown a statistically significant and clinically meaningful survival benefit. It is our hope that we will see survival gains when immune checkpoint inhibitors are moved into primary treatment for locally advanced disease and combined with chemoradiation and/or used as a maintenance therapy following completion of chemoradiation.