Sex differences in immunotherapy plus chemotherapy: A systematic review and meta-analysis
Salah Ameen Abdu1, Wafa Ali Asaad2, Muaadh Wdaan1
1Research Center of Oral and Maxillofacial Tumor, Xiangya Hospital, Central South University, Changsha 410008, China.
Critical Reviews in Oncology/Hematology
|December 8, 2025
Summary
Immune checkpoint inhibitors plus chemotherapy benefit both males and females equally. Treatment decisions should focus on tumor characteristics, not biological sex, for equitable cancer care.
Area of Science:
- Oncology
- Immunology
- Clinical Trials
Background:
- Sex-based differences in immune responses and cancer biology may impact immunotherapy outcomes.
- Evidence on sex-specific efficacy of immune checkpoint inhibitors plus chemotherapy is incomplete.
Purpose of the Study:
- To evaluate the efficacy of immune checkpoint inhibitors plus chemotherapy in relation to biological sex.
- To determine if sex influences treatment outcomes in cancer patients receiving combination immunotherapy.
Main Methods:
- Systematic review and meta-analysis of randomized controlled trials (PRISMA guidelines).
- Included trials compared immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone.
- Analysis included sex-stratified survival data, subgroup analyses, and meta-regression.
Main Results:
- Combination therapy significantly improved overall survival and progression-free survival in both males and females.
- Mortality reductions were 24% in males and 22% in females; progression-free survival improved by 39% in males and 34% in females.
- No statistically significant sex-based differences in efficacy were observed across various cancer types, immunotherapy agents, or chemotherapy regimens.
Conclusions:
- Immune checkpoint inhibitors combined with chemotherapy offer comparable survival benefits for male and female cancer patients.
- Treatment decisions should prioritize tumor characteristics over patient sex.
- Results underscore the need for equitable treatment access and continued sex-stratified data in clinical research.
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