Immunotherapy Tolerable after Chemoradiotherapy in Cervical Cancer Patients

A study published in JAMA Oncology assessed the tolerability of sequential immunotherapy following chemoradiotherapy among women with lymph node (LN)–positive cervical cancer.

“Despite standard chemoradiotherapy (CRT), most women with lymph node (LN)–positive cervical cancer experience disease recurrence,” the authors explained. “Immunotherapy is being investigated in the up-front treatment setting.”

This was a prospective phase 1 study that took place in 29 Gynecology Oncology Cooperative Group member institutions. Patients were recruited between Dec. 18, 2012, and Aug. 31, 2016, and had a 14.8-month median follow-up and translational end points. A total of 34 patients with International Federation of Gynecology and Obstetrics stage IB2 to IVA cervical cancer with positive pelvic LNs, para-aortic LNs, or both were initially included in the study, and 13 were excluded because they did not receive ipilimumab. Eligible patients received six weekly doses of cisplatin 40 mg/m2 concurrently with radiotherapy. Following chemotherapy, patients received sequential ipilimumab every three weeks for four total doses; ipilimumab was administered in 3 mg/kg and 10 mg/kg doses to determine the maximum tolerated dose. The primary outcome measure was safety; other outcomes included overall and progression-free survival, and exploratory endpoints included human papillomavirus (HPV) genotype, HLA allele status, and PD-1 expression measured in peripheral blood.

There were 32 women in the intent-to-treat analysis, who had a median age of 50 (range, 26 to 61) years; most patients (n = 22, 69%) were white. Twenty-one women received ipilimumab, all of whom had positive pelvic LN; six (29%) had positive para-aortic LNs. All patients finished chemoradiotherapy to completion. The majority of women who received at least two ipilimumab cycles (n = 18, 86%) finished four ipilimumab cycles, and three (14%) completed two cycles. The maximum tolerated dose of ipilimumab was 10 mg/kg. the rate of self-limiting grade 3 toxic effects among the 21 ipilimumab patients was low (n = 2/21, 9.5%); these effects included lipase increase and dermatitis. Overall survival after 12 months was 90%, and progression-free survival was 81%. There were no correlations between HPV genotype and HLA subtype and progression-free or overall survival. PD-1-expresssing T cells were increased following chemoradiotherapy, and were sustained with ipilimumab.

“This study’s findings suggest that the use of immunotherapy after [chemoradiotherapy] for curative-intent treatment of patients with cervical cancer is tolerable and effective,” concluded the authors. “The results indicated that PD-1 was upregulated after [chemoradiotherapy] and sustained with sequential ipilimumab therapy. These immune findings may help guide future therapies to harness the activated T-cell phenotype in patients with node-positive cervical cancer.”