In the Journals Plus

Patients’ sex may impact efficacy of immune checkpoint inhibitors

Show Citation

May 17, 2018

The magnitude of benefit from immune checkpoint inhibitors for advanced cancer appeared sex dependent, with women experiencing less benefit, according to results from a meta-analysis.

“Both sex and gender can potentially affect the strength of the body’s immune response. On average, women mount stronger immune responses than do men, which results in more rapid clearance of pathogens, explaining the lower severity and prevalence of many infections in women, and their greater response to vaccination than men,” Fabio Conforti, MD, of European Oncology Institute in Milan, said in a press release. “On the other hand, women account for roughly 80% of all patients with systemic autoimmune diseases worldwide. Therefore, it’s possible that differences in the immune system of women and men could be relevant to the natural course of chronic inflammatory conditions such as cancer, and potentially how they respond to drugs.”

The researchers searched PubMed, MEDLINE, Embase and Scopus for randomized controlled trials of immune checkpoint inhibitors — ipilimumab (Yervoy, Bristol-Myers Squibb), tremelimumab (AstraZeneca), nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck) — that included HRs for death by patients’ sex, and they reviewed abstracts and presentations from all major conferences.

The difference in efficacy of immune checkpoint inhibitors between men and women as reported by OS served as the main outcome.

Conforti and colleagues used a random-effects model to calculate the pooled OS HR and 95% CI, and used an interaction test to assess heterogeneity between the two estimates.

The researchers identified 7,133 studies, ultimately reviewing just 20 eligible randomized controlled trials.

These trials included data on 11,351 patients with advanced or metastatic cancers (67% men). Melanoma was the most common type of cancer (n = 3,632; 32%), followed by non-small cell lung cancer (n = 3,482; 31%).

Men treated with immune checkpoint inhibitors had a pooled OS HR of 0.72 (95% CI, 0.65-0.79) compared with males treated in control groups, whereas women treated with immune checkpoint inhibitors had a pooled OS HR of 0.86 (95% CI, 0.79-0.93) compared with females in control groups.

Conforti and colleagues reported a significant difference in efficacy between men and women who received immune checkpoint inhibitors (P = .0019).

The wide variety of solid tumors included in the analysis all have their own confounding baseline characteristics, Omar Abdel-Rahman, MBBCh, MSc, MD, of the department of oncology at University of Calgary Tom Baker Cancer Centre, wrote in an accompanying editorial.

Further, Abdel-Rahman wrote, differing lifestyle and behavioral characteristics may have affected the data.

“Although the article by Conforti and colleagues is a thought-provoking and hypothesis-generating piece of work, caution needs to be exercised before jumping directly to radical conclusions and before changing the current standard of care among approved indications for immune checkpoint inhibitors,” Abdel-Rahman wrote. “Female patients who are otherwise indicated for treatment with any immune checkpoint inhibitor should not be denied treatment solely on the basis of these findings. Further prospective studies that are disease specific and that account thoroughly for potential confounders are needed before a final judgment can be made about the effect of the patient’s sex on the efficacy of immune checkpoint inhibitors.” – by Andy Polhamus

Disclosures: The authors and Abdel-Rahman report no relevant financial disclosures.