Sex differences in the efficacy of immune checkpoint inhibitors in treating patients with non-small cell lung cancer: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LUO Xindong ¹ , HONG Ziqiang ² , CUI Baiqiang ² , CHENG Tao ² ,  GOU Yunjiu ²

1. The First Clinical Department of Gansu University of Traditional Chinese Medicine, Lanzhou, 730000, P. R. China;
2. Department of Thoracic Surgery, Gansu Provincial Hospital, Lanzhou, 730000, P. R. China;

Corresponding author：

GOU Yunjiu, Email: gouyunjiu@163.com

Keywords：

Sex differences; immune checkpoint inhibitors; non-small cell lung cancer; systematic review/meta-analysis

DOI：

10.7507/1007-4848.202303033

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically review the sex differences in efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) patients. Methods We conducted a computer search of Medline, The Cochrane Library, and EMbase from inception to November 2022 to identify randomized controlled trials (RCTs) assessing the efficacy of ICIs in patients with NSCLC. A meta-analysis was performed using RevMan 5.4 software. Results Finally 16 RCTs with a total of 9 653 patients were included, and the modified Jadad scale score was≥4 points. Meta-analysis results showed that in female NSCLC patients receiving immune therapy, the median overall survival (OS) [HR=0.72, 95%CI (0.61, 0.85), P<0.001] was longer than that in males [HR=0.73, 95%CI (0.69, 0.78), P<0.001]. Males [HR=0.64, 95%CI (0.58, 0.71), P<0.001] had an advantage over females [HR=0.76, 95%CI (0.57, 1.03), P=0.760] in median progression-free survival (PFS). Conclusion Females receiving ICIs have an advantage over males in terms of median OS. However, males tend to derive greater benefit from ICIs in terms of median PFS.

Citation： LUO Xindong, HONG Ziqiang, CUI Baiqiang, CHENG Tao, GOU Yunjiu. Sex differences in the efficacy of immune checkpoint inhibitors in treating patients with non-small cell lung cancer: A systematic review and meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2025, 32(2): 237-243. doi: 10.7507/1007-4848.202303033 Copy

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2.	Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2017, 28(suppl_4): iv1-iv21.
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4.	Hanna N, Johnson D, Temin S, et al. Systemic therapy for stage Ⅳ non-small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update summary. J Oncol Pract, 2017, 13(12): 832-837.
5.	Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science, 2018, 359(6382): 1350-1355.
6.	Arterburn JB, Prossnitz ER. G Protein-coupled estrogen receptor GPER: Molecular pharmacology and therapeutic applications. Annu Rev Pharmacol Toxicol, 2023, 63: 295-320.
7.	Cosci I, Grande G, Di Nisio A, et al. Cutaneous melanoma and hormones: Focus on sex differences and the testis. Int J Mol Sci, 2022, 24(1): 599.
8.	Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol, 2016, 16(10): 626-638.
9.	Markle JG, Fish EN. SeXX matters in immunity. Trends Immunol, 2014, 35(3): 97-104.
10.	Özdemir BC, Csajka C, Dotto GP, et al. Sex differences in efficacy and toxicity of systemic treatments: An undervalued issue in the era of precision oncology. J Clin Oncol, 2018, 36(26): 2680-2683.
11.	Conforti F, Pala L, Bagnardi V, et al. Cancer immunotherapy efficacy and patients' sex: A systematic review and meta-analysis. Lancet Oncol, 2018, 19(6): 737-746.
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14.	Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med, 2015, 373(2): 123-135.
15.	Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial. Lancet, 2017, 389(10066): 255-265.
16.	Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage ⅢNSCLC. N Engl J Med, 2018, 379(24): 2342-2350.
17.	Barlesi F, Vansteenkiste J, Spigel D, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): An open-label, randomised, phase 3 study. Lancet Oncol, 2018, 19(11): 1468-1479.
18.	Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med, 2018, 378(22): 2078-2092.
19.	Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med, 2019, 381(21): 2020-2031.
20.	Reck M, Rodríguez-Abreu D, Robinson AG, et al. Updated analysis of KEYNOTE-024: Pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol, 2019, 37(7): 537-546.
21.	West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol, 2019, 20(7): 924-937.
22.	Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med, 2020, 383(14): 1328-1339.
23.	Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): An international, randomised, open-label, phase 3 trial. Lancet Oncol, 2021, 22(2): 198-211.
24.	Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): A randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med, 2021, 9(3): 305-314.
25.	de Castro G, Kudaba I, Wu YL, et al. Five-year outcomes with pembrolizumab versus chemotherapy as first-line therapy in patients with non-small-cell lung cancer and programmed death ligand-1 tumor proportion score≥1% in the KEYNOTE-042 study. J Clin Oncol, 2023, 41(11): 1986-1991.
26.	Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: A randomized, controlled, double-blind phase 3 trial. Nat Med, 2022, 28(11): 2374-2380.
27.	O'Brien M, Paz-Ares L, Marreaud S, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage ⅠB-ⅢA non-small-cell lung cancer (PEARLS/KEYNOTE-091): An interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol, 2022, 23(10): 1274-1286.
28.	Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: Durvalumab after chemoradiotherapy in stage Ⅲnon-small-cell lung cancer. J Clin Oncol, 2022, 40(12): 1301-1311.
29.	刘建成, 马洁. 肿瘤免疫治疗的研究进展. 癌症进展, 2014, (6): 518-521.Liu JC, Ma J. Research progress on tumor immunotherapy. Oncol Progr, 2014(6): 518-521.
30.	Ugurel S, Röhmel J, Ascierto PA, et al. Survival of patients with advanced metastatic melanoma: The impact of novel therapies. Eur J Cancer, 2016, 53: 125-134.
31.	Fusi A, Dalgleish A. The importance for immunoregulation for long-term cancer control. Future Oncol, 2017, 13(18): 1619-1632.
32.	Keir ME, Liang SC, Guleria I, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med, 2006, 203(4): 883-895.
33.	Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med, 2012, 366(26): 2443-2454.
34.	Xia L, Liu Y, Wang Y. PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: Current status and future directions. Oncologist, 2019, 24(Suppl 1): S31-S41.
35.	Wang C, Qiao W, Jiang Y, et al. Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non-small cell lung cancer. Cancer Med, 2019, 8(8): 4023-4031.
36.	Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: When a chromosome makes the difference. Nat Rev Immunol, 2010, 10(8): 594-604.
37.	Case LK, Toussaint L, Moussawi M, et al. Chromosome y regulates survival following murine coxsackievirus b3 infection. G3 (Bethesda), 2012, 2(1): 115-121.
38.	Talaat RM, Mohamed SF, Bassyouni IH, et al. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine, 2015, 72(2): 146-153.
39.	Jaillon S, Berthenet K, Garlanda C. Sexual dimorphism in innate immunity. Clin Rev Allergy Immunol, 2019, 56(3): 308-321.
40.	Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, et al. Male reproductive disorders and fertility trends: Influences of environment and genetic susceptibility. Physiol Rev, 2016, 96(1): 55-97.
41.	Slominski A, Zbytek B, Nikolakis G, et al. Steroidogenesis in the skin: Implications for local immune functions. J Steroid Biochem Mol Biol, 2013, 137: 107-123.
42.	Hughes M, Pauling JD, Armstrong-James L, et al. Gender-related differences in systemic sclerosis. Autoimmun Rev, 2020, 19(4): 102494.
43.	Fan H, Dong G, Zhao G, et al. Gender differences of B cell signature in healthy subjects underlie disparities in incidence and course of SLE related to estrogen. J Immunol Res, 2014, 2014: 814598.
44.	Abdullah M, Chai PS, Chong MY, et al. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell Immunol, 2012, 272(2): 214-219.
45.	Teixeira D, Longo-Maugeri IM, Santos JL, et al. Evaluation of lymphocyte levels in a random sample of 218 elderly individuals from São Paulo city. Rev Bras Hematol Hemoter, 2011, 33(5): 367-371.
46.	Furman D, Hejblum BP, Simon N, et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A, 2014, 111(2): 869-874.
47.	Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage Ⅳ or recurrent non-small-cell lung cancer. N Engl J Med, 2017, 376(25): 2415-2426.
48.	Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med, 2016, 375(19): 1823-1833.
49.	Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet, 2016, 387(10027): 1540-1550.
50.	Govindan R, Szczesna A, Ahn MJ, et al. Phase Ⅲ trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol, 2017, 35(30): 3449-3457.
51.	Grassadonia A, Sperduti I, Vici P, et al. Effect of gender on the outcome of patients receiving immune checkpoint inhibitors for advanced cancer: A systematic review and meta-analysis of phase Ⅲrandomized clinical trials. J Clin Med, 2018, 7(12): 542.
52.	Wu Y, Ju Q, Jia K, et al. Correlation between sex and efficacy of immune checkpoint inhibitors (PD-1 and CTLA-4 inhibitors). Int J Cancer, 2018, 143(1): 45-51.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2017, 28(suppl_4): iv1-iv21.
3. Wang C, Yu X, Wang W. A meta-analysis of efficacy and safety of antibodies targeting PD-1/PD-L1 in treatment of advanced nonsmall cell lung cancer. Medicine (Baltimore), 2016, 95(52): e5539.
4. Hanna N, Johnson D, Temin S, et al. Systemic therapy for stage Ⅳ non-small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update summary. J Oncol Pract, 2017, 13(12): 832-837.
5. Ribas A, Wolchok JD. Cancer immunotherapy using checkpoint blockade. Science, 2018, 359(6382): 1350-1355.
6. Arterburn JB, Prossnitz ER. G Protein-coupled estrogen receptor GPER: Molecular pharmacology and therapeutic applications. Annu Rev Pharmacol Toxicol, 2023, 63: 295-320.
7. Cosci I, Grande G, Di Nisio A, et al. Cutaneous melanoma and hormones: Focus on sex differences and the testis. Int J Mol Sci, 2022, 24(1): 599.
8. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol, 2016, 16(10): 626-638.
9. Markle JG, Fish EN. SeXX matters in immunity. Trends Immunol, 2014, 35(3): 97-104.
10. Özdemir BC, Csajka C, Dotto GP, et al. Sex differences in efficacy and toxicity of systemic treatments: An undervalued issue in the era of precision oncology. J Clin Oncol, 2018, 36(26): 2680-2683.
11. Conforti F, Pala L, Bagnardi V, et al. Cancer immunotherapy efficacy and patients' sex: A systematic review and meta-analysis. Lancet Oncol, 2018, 19(6): 737-746.
12. Wallis CJD, Butaney M, Satkunasivam R, et al. Association of patient sex with efficacy of immune checkpoint inhibitors and overall survival in advanced cancers: A systematic review and meta-analysis. JAMA Oncol, 2019, 5(4): 529-536.
13. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med, 2015, 373(17): 1627-1639.
14. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med, 2015, 373(2): 123-135.
15. Rittmeyer A, Barlesi F, Waterkamp D, et al. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial. Lancet, 2017, 389(10066): 255-265.
16. Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage ⅢNSCLC. N Engl J Med, 2018, 379(24): 2342-2350.
17. Barlesi F, Vansteenkiste J, Spigel D, et al. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): An open-label, randomised, phase 3 study. Lancet Oncol, 2018, 19(11): 1468-1479.
18. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med, 2018, 378(22): 2078-2092.
19. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med, 2019, 381(21): 2020-2031.
20. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Updated analysis of KEYNOTE-024: Pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol, 2019, 37(7): 537-546.
21. West H, McCleod M, Hussein M, et al. Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): A multicentre, randomised, open-label, phase 3 trial. Lancet Oncol, 2019, 20(7): 924-937.
22. Herbst RS, Giaccone G, de Marinis F, et al. Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC. N Engl J Med, 2020, 383(14): 1328-1339.
23. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): An international, randomised, open-label, phase 3 trial. Lancet Oncol, 2021, 22(2): 198-211.
24. Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): A randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med, 2021, 9(3): 305-314.
25. de Castro G, Kudaba I, Wu YL, et al. Five-year outcomes with pembrolizumab versus chemotherapy as first-line therapy in patients with non-small-cell lung cancer and programmed death ligand-1 tumor proportion score≥1% in the KEYNOTE-042 study. J Clin Oncol, 2023, 41(11): 1986-1991.
26. Gogishvili M, Melkadze T, Makharadze T, et al. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: A randomized, controlled, double-blind phase 3 trial. Nat Med, 2022, 28(11): 2374-2380.
27. O'Brien M, Paz-Ares L, Marreaud S, et al. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage ⅠB-ⅢA non-small-cell lung cancer (PEARLS/KEYNOTE-091): An interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol, 2022, 23(10): 1274-1286.
28. Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: Durvalumab after chemoradiotherapy in stage Ⅲnon-small-cell lung cancer. J Clin Oncol, 2022, 40(12): 1301-1311.
29. 刘建成, 马洁. 肿瘤免疫治疗的研究进展. 癌症进展, 2014, (6): 518-521.Liu JC, Ma J. Research progress on tumor immunotherapy. Oncol Progr, 2014(6): 518-521.
30. Ugurel S, Röhmel J, Ascierto PA, et al. Survival of patients with advanced metastatic melanoma: The impact of novel therapies. Eur J Cancer, 2016, 53: 125-134.
31. Fusi A, Dalgleish A. The importance for immunoregulation for long-term cancer control. Future Oncol, 2017, 13(18): 1619-1632.
32. Keir ME, Liang SC, Guleria I, et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J Exp Med, 2006, 203(4): 883-895.
33. Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med, 2012, 366(26): 2443-2454.
34. Xia L, Liu Y, Wang Y. PD-1/PD-L1 blockade therapy in advanced non-small-cell lung cancer: Current status and future directions. Oncologist, 2019, 24(Suppl 1): S31-S41.
35. Wang C, Qiao W, Jiang Y, et al. Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non-small cell lung cancer. Cancer Med, 2019, 8(8): 4023-4031.
36. Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: When a chromosome makes the difference. Nat Rev Immunol, 2010, 10(8): 594-604.
37. Case LK, Toussaint L, Moussawi M, et al. Chromosome y regulates survival following murine coxsackievirus b3 infection. G3 (Bethesda), 2012, 2(1): 115-121.
38. Talaat RM, Mohamed SF, Bassyouni IH, et al. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine, 2015, 72(2): 146-153.
39. Jaillon S, Berthenet K, Garlanda C. Sexual dimorphism in innate immunity. Clin Rev Allergy Immunol, 2019, 56(3): 308-321.
40. Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, et al. Male reproductive disorders and fertility trends: Influences of environment and genetic susceptibility. Physiol Rev, 2016, 96(1): 55-97.
41. Slominski A, Zbytek B, Nikolakis G, et al. Steroidogenesis in the skin: Implications for local immune functions. J Steroid Biochem Mol Biol, 2013, 137: 107-123.
42. Hughes M, Pauling JD, Armstrong-James L, et al. Gender-related differences in systemic sclerosis. Autoimmun Rev, 2020, 19(4): 102494.
43. Fan H, Dong G, Zhao G, et al. Gender differences of B cell signature in healthy subjects underlie disparities in incidence and course of SLE related to estrogen. J Immunol Res, 2014, 2014: 814598.
44. Abdullah M, Chai PS, Chong MY, et al. Gender effect on in vitro lymphocyte subset levels of healthy individuals. Cell Immunol, 2012, 272(2): 214-219.
45. Teixeira D, Longo-Maugeri IM, Santos JL, et al. Evaluation of lymphocyte levels in a random sample of 218 elderly individuals from São Paulo city. Rev Bras Hematol Hemoter, 2011, 33(5): 367-371.
46. Furman D, Hejblum BP, Simon N, et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A, 2014, 111(2): 869-874.
47. Carbone DP, Reck M, Paz-Ares L, et al. First-line nivolumab in stage Ⅳ or recurrent non-small-cell lung cancer. N Engl J Med, 2017, 376(25): 2415-2426.
48. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med, 2016, 375(19): 1823-1833.
49. Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet, 2016, 387(10027): 1540-1550.
50. Govindan R, Szczesna A, Ahn MJ, et al. Phase Ⅲ trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol, 2017, 35(30): 3449-3457.
51. Grassadonia A, Sperduti I, Vici P, et al. Effect of gender on the outcome of patients receiving immune checkpoint inhibitors for advanced cancer: A systematic review and meta-analysis of phase Ⅲrandomized clinical trials. J Clin Med, 2018, 7(12): 542.
52. Wu Y, Ju Q, Jia K, et al. Correlation between sex and efficacy of immune checkpoint inhibitors (PD-1 and CTLA-4 inhibitors). Int J Cancer, 2018, 143(1): 45-51.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Sex differences in the efficacy of immune checkpoint inhibitors in treating patients with non-small cell lung cancer: A systematic review and meta-analysis

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