With New Options for the Treatment of Cervical Cancer, Considering Individual Patient Characteristics is Essential

Carefully considering patients’ individual needs and disease characteristics is essential when selecting a therapeutic regimen, according to an expert panel at the Society of Gynecologic Cancers 2022 Annual Meeting on Women’s Cancer.

The FDA approved 2 new agents for cervical cancer in 2021, a number that moderator Bradley Monk, MD, FACS, FACOG, said was “unprecedented.” In his 35 years working in the field, Monk said he has seen the treatment of cervical cancer progress significantly, with new data now emerging consistently.

Similar to the COVID-19 pandemic, Monk said it is essential to educate patients on the importance of prevention and testing for human papillomavirus (HPV) because it can cause cervical cancer.

“If COVID has taught us anything, it’s that if you don’t get vaccinated, you might die,” Monk said in the presentation. “And that’s the same with HPV.”

Monk noted that the death rate from cervical cancer has dropped by more than 50% since 1975. Between 2007 and 2016, in fact, the death rate decreased by about 1% each year in women 50 years of age and older but remained stable in women younger than 50 years of age.

Monk also emphasized the importance of testing for programmed death-ligand 1 (PD-L1) expression in patients with cervical cancer but said that this expression is not a single entity. To make educated decisions about treatment, it is essential to know the antibody and scoring method, as well as the threshold.

“You cannot make a statement about PD-L1 testing unless you say the method, the threshold, and the antibody,” Monk said.

Next, panelist Krishnansu Tewari, MD, discussed a case presentation of first-line therapy options. In the case, a 42-year-old Caucasian woman with 3 young children presented with pelvic discomfort and cough. Scans found right paracolic gutter disease, which Tewari said probably contributed to her discomfort, as well as hilar adenopathy and supraclavicular adenopathy. The patient had been diagnosed with stage IIIc squamous cell carcinoma of the cervix 2 years previously.

Neither stereotactic radiosurgery nor pelvic exenteration would be appropriate for this patient based on her tumor burden and the fact that she had disease outside of the pelvis. Based on this, Tewari said systemic treatment would be best, potentially including chemotherapy, anti-angiogenesis therapy, or immunotherapy.

Tewari reviewed some data around chemotherapy, including the 2009 GOG-0204 study, which established cisplatin and paclitaxel as the chemotherapy palliative standard for women with metastatic cervical cancer. The JCOG-0505 study then established non-inferiority of carboplatin among patients who were previously treated with cisplatin. Therefore, the patient received carboplatin plus paclitaxel until progression.

“Those two studies, I think, are critical in helping us determine how we’re going to treat this patient moving forward,” Tewari said.

Tewari then discussed anti-angiogenesis therapy with bevacizumab, the use of which is based on clinical, pathologic, therapeutic, and molecular rationale. The GOG-0240 study found significant improvements in overall survival (OS) and progression-free survival with the addition of bevacizumab to chemotherapy. Based on these findings, in August of 2014, bevacizumab became the first targeted agent approved in gynecologic cancer. Tewari said the patient received bevacizumab in addition to her chemotherapy regimen.

Tewari also discussed the use of immunotherapy. KEYNOTE-826 was a confirmatory trial looking at the efficacy and tolerability of a chemotherapy doublet, bevacizumab, and pembrolizumab, compared with the chemotherapy doublet with or without bevacizumab. In the intent-to-treat population, researchers found that the hazard ratio for disease progression or death was reduced by 35%, and it decreased by 38% in patients with a PD-L1 combined positive score of 1 or greater.

Notably, Tewari pointed out that pembrolizumab took just 113 days to receive FDA approval. Based on these data and the patient’s combined positive score of 20, she then received the chemotherapy double, bevacizumab, and pembrolizumab. She received 3 cycles of this quadruplet therapy.

Finally, presenter Shannon Westin, MD, MPH, FACOG, discussed second-line options for patients with cervical cancer. In her case study, a 52-year-old patient with stage IV grade 3 squamous cell carcinoma of the cervix had previously received 6 cycles of paclitaxel, cisplatin, and bevacizumab and had evidence of near complete response. At 6 months, she noted moderate abdominal pain and imaging found recurrent peritoneal carcinomatosis, liver lesions, and omental and diaphragmatic disease. The tumor was PD-L1 positive.

Like Tewari, Westin reviewed the rationale for pembrolizumab in the second-line setting. The KEYNOTE-028 trial investigated single-agent pembrolizumab in advanced or recurrent disease and found a positive response rate, which was subsequently confirmed in the KEYNOTE-158 study. This 14% confirmatory response rate allowed for pembrolizumab to receive FDA approval for the treatment of PD-L1 positive recurrent or metastatic cervical cancer, in addition to a subsequent approval for a 6-week dosing strategy.

The EMPOWER study investigated cemiplimab with a primary endpoint of OS and found improved OS with a median of 12 months in the treatment arm. Westin did point out that it is difficult to know whether this treatment definitively does not work in a PD-L1-negative population because approximately 40% of patients in the trial had not received this testing.

The benefit of cemiplimab was also consistent, particularly across patients with prior bevacizumab treatment. An improved response rate was seen across the board, with a 16% response rate.

Most importantly, Westin noted that patients treated with cemiplimab had improved global health score/quality of life. Patients reported improved fatigue, nausea, vomiting, pain, insomnia, appetite loss, and constipation, and all of these symptoms factored the use of cemiplimab over clinician’s choice of chemotherapy.

“Obviously we want patients to live longer, it’s about survival,” Westin said. “But this is good survival.”

Based on these data, the patient in Westin’s case study started on pembrolizumab and noted increased cough and shortness of breath at 6 months. She was diagnosed with grade 2 pneumonitis, which Westin said was treated by withholding pembrolizumab and administering low-dose corticosteroids. Considering re-dosing would be appropriate with a grade 2 immune-related adverse event.

REFERENCE

Monk B, Tewari K, Westin S. The Afternoon in Gyn Onc: The Evolution of Cervical Cancer. Presented at Society of Gynecologic Oncology 2022 Annual Meeting on Women’s Cancer. March 19, 2022.