Nivolumab May Induce Promising Efficacy Outcomes in Certain Gynecologic Malignancies

Treatment with nivolumab (Opdivo) demonstrated promising efficacy results among patients with recurrent/metastatic cervical and vaginal or vulvar cancers, according to phase I/II study results published in the Journal of Clinical Oncology.

The monoclonal antibody may even have the potential to replace chemotherapy for some of these cancers. “I suspect that immunotherapy will likely replace chemotherapy in these cancers and I am excited about the future of immunotherapy in these cancers,” corresponding author R. Wendel Naumann, MD, professor and associate director of gynecologic oncology at the Levine Cancer Institute at Atrium Health in North Carolina, said to Cancer Network™.

Naumann et al also concluded that nivolumab should be further investigated for use in deadly and persistent cervical, vaginal, and vulvar cancers. “Given the lack of effective therapy and low survival rates for patients with metastatic disease in these gynecologic cancers, the results reported here are of strong clinical interest and underscore the growing role of immune checkpoint inhibitors in this patient population,” the investigators wrote.

The phase I/II CheckMate 358 trial included 24 patients – 19 with cervical cancer, and 5 with vaginal or vulvar forms of the disease. Most women had previous systemic therapy for metastatic disease (cervical, 78.9%; vaginal/vulvar, 80.0%). Patients who were known to have human papillomavirus (HPV)-negative tumors were ineligible for the study.

Objective response rate served as the primary endpoint, and secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Safety and patient-reported outcomes were also exploratory endpoints for the study.

Patients received 240 mg nivolumab every 2 weeks. Physical examinations were performed within 14 days before the first dose was administered, and again for every 2 weeks afterward.

ORR, assessed statistically using binomial response rate and the Clopper-Pearson methodology, was 26.3% for patients with cervical cancer (95% CI, 9.1-51.2) and 20.0% for those with vaginal or vulvar cancers (95% CI, 0.5-71.6).

At a median follow-up of 19.2 months, median DOR was not reached in the 5 patients with cervical cancer who experienced a response. In the vaginal/vulvar cohort, median DOR was 5.0 months in 1 patient.

Median OS, calculated using the Kaplan-Meier estimator method, was 21.9 months for the cervical cohort (95% CI, 15.1 months to not reached), as compared to previous statistics showing a medial overall survival of 6.5 months to 13.3 months for chemotherapy-only regimens.

Lastly, efficacy outcomes appeared to be unrelated to PD-L1 expression, since one-third of the patients tested were negative for the ligand, Naumann  noted, adding that the work could completely change the treatment landscape for the diseases.

Any-grade treatment-related adverse events (TRAEs) were reported in 12 of 19 patients (63.2%) in the cervical cohort and all 5 patients in the vaginal/vulvar cohort. The most common TRAE was diarrhea in the cervical cohort, and decreased appetite in the vaginal or vulvar group.

Patient-reported outcomes demonstrated global health status was stable at week 9 compared with baseline, as well as physical functioning, emotional functioning, and social functioning. However, clinically meaningful deterioration was observed in role functioning and cognitive functioning.

In addition, patients reported having experienced clinically meaningful improvement in pain and constipation; a clinically meaningful deterioration in fatigue; and stability of nausea and vomiting, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties.

With this, the treatment gap that nivolumab may be able to fill is critical for patients, Naumann said.

“Right now, there is no standard therapy for second-line systemic therapy for metastatic cervical cancer,” he explained. “Response rates and overall survival are poor in this setting and these patients are often women with young children. Some of the complete responses (shown in the data) are durable and ongoing for more than 1 year.”