HPV Vaccination and Anti-programmed Cell Death 1 Inhibition Improve Survival in Patients With Invasive HPV-16

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Preparing a vaccination.
Preparing a vaccination.

Vaccination against human papilloma virus (HPV) alone is not effective in combating invasive HPV-driven cancer. Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies have shown promising results, but only produces tumor regression in a minority of patients with HPV-related cancer. In a recent study published in JAMA Oncology, researchers investigated if the efficacy of programmed cell death 1 immune checkpoint inhibition was increased by a tumor specific vaccine in patients with incurable HPV-16 cancer.

A total of 24 patients with incurable HPV-16 cancer were enrolled in a phase 2 clinical trial from December 23, 2015, to December 12, 2016, with a 12-month follow-up period through August 31, 2017. The HPV-16 vaccine, ISA101 was administered subcutaneously on days 1, 22, and 50, and the PD-1 inhibitor, nivolumab was administered intravenously every 2 weeks starting at day 8 for a total of 1 year.

The overall response rate to treatment was 33%, with a median duration of response of 10.3 months. At the time of publication, 5 of 8 patients remained responsive to treatment. The median progression-free survival was 2.7 months; and the median overall survival was 17.5 months. Two patients experienced adverse effects of grades 3-4 toxicity and were discontinued from the nivolumab therapy. 

According to the authors the results are, “promising compared with PD-1 inhibition alone in similar patients. A randomized clinical trial to confirm the contribution of HPV-16 vaccination to tumoricidal effects of PD-1 inhibition is warranted for further study.”

Reference

Massarelli E, William W, Johnson F, et al.Combining immune checkpoint blockade and tumor-specific vaccine for patients with incurable human papillomavirus 16–related cancer. A phase 2 clinical trial[published online September 27, 2018]. JAMA Oncol. doi:10.1001/jamaoncol.2018.4051

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