Curative-Intent Immunotherapy Outcomes Did Not Differ by Sex

A systematic review and meta-analysis found no statistically significant differences between female and male patients in survival or recurrence-related outcomes associated with immune checkpoint inhibitors (ICIs) used with curative intent for solid tumors. The findings were published in JAMA Network Open.

The analysis included 62 reports from 38 randomized phase 3 trials and 31,721 patients, of whom 29.7% were female and 70.3% were male. Eligible trials evaluated ICIs in non-sex-specific solid tumors treated with definitive local therapy, including surgery, radiotherapy, or chemoradiotherapy. ICI use could be neoadjuvant, perioperative, adjuvant, consolidation, concomitant with radiotherapy or chemoradiotherapy, or administered before those modalities.

Across the full population, ICIs were associated with improved overall survival (hazard ratio [HR], 0.83; 95% CI, 0.79-0.89) and a combined outcome comprising disease-free, event-free, progression-free, and recurrence-free survival (HR, 0.73; 95% CI, 0.68-0.77). For overall survival, pooled HRs were 0.76 (95% CI, 0.67-0.86) among female patients and 0.78 (95% CI, 0.72-0.85) among male patients. Corresponding HRs for the combined outcome were 0.74 (95% CI, 0.69-0.79) and 0.73 (95% CI, 0.67-0.78), respectively.

In exploratory sensitivity analyses restricted to surgery-only trials, the HRs with neoadjuvant or perioperative ICIs were 0.77 (95% CI, 0.69-0.86) for overall survival and 0.64 (95% CI, 0.57-0.73) for the combined outcome, compared with 0.84 (95% CI, 0.78-0.91) and 0.74 (95% CI, 0.68-0.81), respectively, with adjuvant-only treatment. The investigators cautioned that no formal statistical comparison between these approaches was performed. They also described the combined outcome as an approximate measure of disease control because endpoint selection and definitions varied among trials.

Interpretation of the sex analysis was limited by female underrepresentation and by the fact that none of the included trials was designed or powered to assess sex differences. Other limitations included the absence of a formal study-level risk-of-bias assessment and individual patient data. The authors called for adequate female representation and prespecified, adequately powered sex-based subgroup analyses in future studies.

Source: Hollinger AM, Gerard CL, Andreas VJ, et al. Sex, timing, and outcomes of curative-intent immunotherapy: a systematic review and meta-analysis. JAMA Netw Open. 2026;9(9):e2632635. doi:10.1001/jamanetworkopen.2026.32635