Sex and risk of hyperprogressive disease in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.
Hyperprogressive disease (HPD) refers to a phenomenon characterized by a significant acceleration in tumor growth during treatment with immune-checkpoint inhibitors (ICIs), far exceeding the pre-treatment growth rate, leading to rapid deterioration in the patient's condition. HPD typically occurs within the first two months of treatment and often results in early mortality. While sex differences in immune responses have been extensively studied, the relationship between sex and HPD risk remains unclear.
We systematically searched MEDLINE (PubMed), Embase, and Scopus databases to identify studies reporting HPD in patients treated with ICIs, with available gender-stratified data. The search encompassed all records from database inception until 30 June 2025. Meta-analyses were performed using RevMan 5.4.1 software, with pooled odds ratios and 95% confidence intervals calculated under either fixed-effects or random-effects model, depending on heterogeneity. The primary objective was to evaluate the association between biological sex and the risk of HPD. The research protocol has been registered on the PROSPERO platform (CRD420261324007).
This meta-analysis included 20 studies involving 2,291 patients (1,612 male patients and 679 female patients), all of which were retrospective. The overall incidence of HPD was 18.67% in male patients and 18.26% in female patients. Pooled analysis revealed no statistically significant association between biological sex and the risk of HPD development (I 2 = 27%; p = 0.13).
Our findings demonstrate that sex should not be considered a determinative factor for HPD risk in patients receiving ICIs.
We systematically searched MEDLINE (PubMed), Embase, and Scopus databases to identify studies reporting HPD in patients treated with ICIs, with available gender-stratified data. The search encompassed all records from database inception until 30 June 2025. Meta-analyses were performed using RevMan 5.4.1 software, with pooled odds ratios and 95% confidence intervals calculated under either fixed-effects or random-effects model, depending on heterogeneity. The primary objective was to evaluate the association between biological sex and the risk of HPD. The research protocol has been registered on the PROSPERO platform (CRD420261324007).
This meta-analysis included 20 studies involving 2,291 patients (1,612 male patients and 679 female patients), all of which were retrospective. The overall incidence of HPD was 18.67% in male patients and 18.26% in female patients. Pooled analysis revealed no statistically significant association between biological sex and the risk of HPD development (I 2 = 27%; p = 0.13).
Our findings demonstrate that sex should not be considered a determinative factor for HPD risk in patients receiving ICIs.