R. Wendel Naumann, MD
With few chemotherapy options available for patients with cervical cancer, R. Wendel Naumann, MD, said during the 2020 SGO Winter Meeting that immunotherapy represents an attractive treatment option in the landscape.
Naumann, professor and director of minimally invasive surgery in gynecologic oncology with Levine Cancer Institute, Carolinas Medical Center, Atrium Health, noted that chemotherapy has proven to be largely ineffective in this disease.
An analysis of 3 Gynecologic Oncology Group studies that included 428 women who received standard cisplatin-based combination chemotherapy for advanced or recurrent cervical carcinoma showed that, even in low-risk patients, the objective response rate (ORR) is 43%, along with a median progression-free survival (PFS) of 7 months and a median overall survival (OS) of 12 months.1
Furthermore, there is no evidence that chemotherapy improves OS compared with best supportive care for recurrent disease, Naumann said.
He explained that immunotherapy makes sense in cervical cancer—a virally induced tumor that should be highly angiogenic. Virus-induced cancers generally make good targets for immunotherapy because viral proteins are strong immune stimulants.
In light of the “dismal” results with chemotherapy, Naumann called immunotherapy “an exciting option.”
“One of the things tumors have to do is evade apoptosis,” he said. “We know that the immune response is important, particularly for these virally induced cancers.”
In the KEYNOTE-158 trial, investigators evaluated pembrolizumab (Keytruda) for patients with patients with advanced cervical squamous cell cancer (n = 98). Patients received 200 mg of pembrolizumab every 3 weeks for 24 months or until withdrawal of consent, confirmed radiographic progression, unacceptable toxicity, or investigator decision.2
Eighty-four percent of patients were found to be positive for PD-L1.
Results showed that the ORR was 12.2% (95% CI, 6.5-20.4) with 3 complete responses and 9 partial responses. Overall, the median PFS was 2.1 months (95% CI, 2.0-2.1) and the median OS of 9.4 months (95% CI, 7.7-13.1).
All 12 responses were in patients with PD-L1–positive tumors, for an ORR of 14.6% (95% CI, 7.8-24.2). The median OS was 11.1 months (95% CI, 9.1-14.1) in the PD-L1–positive population.
Based on these preliminary data, the FDA granted an accelerated approval in June 2018 to pembrolizumab for the treatment of patients with advanced cervical cancer who have disease progression on or after chemotherapy, whose tumors express PD-L1 (combined positive score ≥1).
Despite this advance, there is no established standard of care for patients with recurrent or metastatic cervical cancer due to limited responses. Furthermore, vaginal and vulvar cancers are rare, and few clinical trials include these patient populations; therefore, there is a lack of robust trial data regarding these patients.
Investigators in the phase I/II CheckMate-358 trial sought to provide clinical evidence showing the value of nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy) in patients with recurrent or metastatic cervical, vaginal, and vulvar cancer.
In the nivolumab-alone cohort, 24 patients received 10 mg of intravenous nivolumab every 2 weeks for a maximum of 2 years, or until disease progression or unacceptable toxicity. The median duration of treatment was 5.6 months in the cervical cancer cohort and 6.7 months in the vaginal/vulvar cancer cohort.
In the cervical cancer cohort (n = 19), 37.5% of patients had PD-L1–negative tumors and 42% had undergone ≥2 lines of systemic therapy.
The ORR was 26.3% (95% CI, 9.1-51.2) in the cervical cancer arm and 20.0% (95% CI, 0.5-71.6) in the vaginal/vulvar cancer arm (n = 5).3
At a median follow-up of 19.2 months, the median duration of response (DOR) was not reached in the cervical arm and was 5.0 months in the vaginal/vulvar cancer arm.
The median PFS in the cervical cancer group was 5.1 months (95% CI, 1.9-9.1) with a median OS of 21.9 months (95% CI, 15.1-not reached). Because of the small number of patients in the vaginal/vulvar cancer cohort, the median PFS and OS were not calculated.
“We saw several durable, long lasting responses,” Naumann said. “We saw 1 response in the vulvar carcinoma group and another that was close—we only had 5 patients in that cohort.”