Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: Results of a phase 2 study.

BACKGROUND: Immunotherapy has changed the therapeutic landscape in oncology. Advanced uterine leiomyosarcoma (ULMS) remains an incurable disease in most cases, and despite new drug approvals, improvements in overall survival have been modest at best. The goal of this study was to evaluate programmed-death 1 (PD-1) inhibition with nivolumab in this patient population. METHODS: This single-center phase 2 trial completed enrollment between May and October 2015. Patients received 3 mg/kg of intravenous nivolumab on day 1 of each 2-week cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate. We assessed PD-1, PD-ligand 1 (PD-L1), and PD-L2 expression in archival tumor samples and variations in immune-phenotyping of circulating immune cells during treatment. RESULTS: Twelve patients were enrolled in the first stage of the 2-stage design. A median of 5 (range, 2-6) 2-week cycles of nivolumab were administered. Of the 12 patients, none responded to treatment. The overall median progression-free survival was 1.8 months (95% confidence interval, 0.8-unknown). The study did not open the second stage due to lack of benefit as defined by the statistical plan. Archival samples were available for 83% of patients. PD-1 (>3% of cells), PD-L1, and PD-L2 (>5% and >10% of tumor cells, respectively) expression were observed in 20%, 20%, and 90% of samples, respectively. No significant differences were observed between pre- and posttreatment cell phenotypes. CONCLUSION: Single-agent nivolumab did not demonstrate a benefit in this cohort of previously treated advanced ULMS patients. Further biomarker-driven approaches and studies evaluating combined immune checkpoint-modulators should be considered. Cancer 2017;123:3285-90. © 2017 American Cancer Society.

Managing stomatitis in patients treated with Mammalian target of rapamycin inhibitors.

Mammalian target of rapamycin (mTOR) inhibitors are a class of targeted cancer therapeutic agents with clinical benefit for multiple tumor types. Oral ulcerations are a common side effect of mTOR inhibitors; however, the clinical findings resemble aphthous stomatitis rather than the mucositis seen with chemotherapy. Consequently, the appearance of aphthous-like oral ulcerations has been referred to as mTOR inhibitor-associated stomatitis (mIAS). The severity of mIAS can be minimized by following common preventive steps and initiating treatment at the first sign of mouth discomfort, thereby reducing the likelihood of treatment discontinuation. mIAS can be managed through prophylactic measures, such as patient education in oral hygiene and avoidance of triggers. Patients who develop mIAS may be treated topically using rinses or other local therapies, including corticosteroids. In severe cases, dose modifications may be required. Oncology nurses have an important role in the management of patients with cancer and are well positioned to offer strategies for minimizing the occurrence and impact of mIAS.