Do Men Benefit More From Immune Checkpoint Inhibition?
A meta-analysis of 20 randomized clinical trials found that men may infer a greater benefit from immune checkpoint inhibition.
A systematic review and meta-analysis of 20 randomized controlled clinical trials of immune checkpoint inhibitors published in The Lancet Oncology found that immune checkpoint inhibitors were associated with larger improvements in overall survival among men compared with women.1
The pooled studies included a number of immune checkpoint inhibitors and a range of cancer types, including ipilimumab, tremelimumab, nivolumab, and pembrolizumab for the treatment of melanoma, lung cancer, kidney cancer, gastric and gastroesophageal junction cancers, head and neck cancers, and urothelial carcinoma. The authors called for better inclusion of women in immunotherapy trials and studies to improve the effectiveness of this class of therapies in women.
At first glance, at least, the sex-specific findings from the current study seem to be consistent with the outcomes from a small retrospective cohort study of patients receiving immunotherapy for metastatic cutaneous melanoma at the Mayo Clinic between 2014 and 2017.2
According to that study, which was presented at the 2018 American Society of Clinical Oncology Annual Meeting, premenopausal women were more likely to experience grade 1 to 2 immune-related adverse events (IRAEs) from PD-1 immune checkpoint inhibitor administration compared with postmenopausal women or men. In addition, the researchers found that premenopausal women were more than 3 times as likely to experience immunotherapy-associated endocrinopathies or diabetic ketoacidosis as men.
Unknown confounding factors might play a role in observed IRAE-rate sex differences, cautioned study author Narjust Duma, MD, a hematology/medical oncology fellow at the Mayo Clinic in Rochester, Minnesota.2 Based on their results, her team plans to pursue a prospective IRAE database study.
The meta-analysis covering the sex-specific topic should also be interpreted with caution, according to Omar Abdel-Rahman, MD, MSc, MBBCh, of Ain Shams University in Cairo, Egypt, and the University of Calgary, Tom Baker Cancer Centre in Canada. Dr Abdel-Rahman is the author of an editorial that accompanied the meta-analysis in the same issue of Lancet Oncology.3
The meta-analysis was “thought-provoking and hypothesis-generating,” Dr Abdel-Rahman told Cancer Therapy Advisor. “But I think it falls short of practice-changing,” he continued. “We have to be cautious prior to embarking on any radical changes in our treatment paradigm or our administration of these agents based only on these data, which [were collected from] patients suffering from multiple tumor types.”