Single-Agent Ipilimumab Ineffective in HPV-Related Advanced Cervical Cancer
Surabhi Dangi-Garimella, PhD
Analysis of the results from an early phase multicenter study have found that while the cytotoxic T-lymphocyte antigen-4 inhibitor, ipilimumab, is safe in women with metastatic or recurrent cervical cancer, it did not improve patient response to treatment.
The phase 1/2 trial, conducted in the United States and Canada, enrolled 42 women with metastatic cervical cancer (29 had squamous cell carcinoma and 13 had adenocarcinoma) whose disease had progressed following at least a single line of platinum-based chemotherapy. A majority of patients (37) whose tissue was available for analysis tested positive for the human papillomavirus (HPV).
Six patients who were part of the safety cohort were treated with 3 mg/kg ipilimumab, every 21 days for 4 cycles; this was followed by a phase 2 cohort of 10 mg/kg ipilimumab, every 21 days for 4 cycles and then 4 cycles of maintenance therapy every 12 weeks among patients who had radiologic response or stabilization. Conducted between December 3, 2012, and September 15, 2015, the study results were analyzed from April 2016 to June 2016 and in July 2017.
Grade 3 toxicities included diarrhea, which was observed in 4 patients. Thirty-four patients were evaluated for an objective response rate, using the Response Evaluation Criteria in Solid Tumors, version 1.1—10 patients continued to have stable disease and only 1 had a partial response. The median progression-free survival and overall survival were 2.5 months (95% CI, 2.1-3.2 months) and 8.5 months (95% CI, 3.6-not reached; 1 patient was still alive), respectively.
Evaluation of the tumor infiltrate for expression of specific immune biomarkers (CD3, CD4, CD8, FoxP3, indoleamine 2,3-dioxygenase, and programmed cell death-ligand 1 found no change or predictive benefit following treatment of patients with ipilimumab. However, flow cytometric analysis of patient peripheral lymphocytes showed an increase in inducible T-cell costimulator, human leukocyte antigen–antigen D related, and programmed cell death-1 during ipilimumab treatment, and the levels of these proteins returned to baseline during the maintenance phase.
The authors conclude that changes in these markers may assist the development of future treatment strategies in this patient population.
Lheureux S, Butler MO, Clarke B, et al. Association of ipilimumab with safety and antitumor activity in women with metastatic or recurrent human papillomavirus–related cervical carcinoma [published online November 16, 2017]. JAMA Oncol. doi: 10.1001/jamaoncol.2017.3776.