Does patient sex affect the treatment outcome of immune checkpoint inhibitors? A Danish, observational melanoma study

Soeren Kjaer Petersen; Christian Rønn Hansen; Eva Ellebaek; Henrik Schmidt; Charlotte Aaquist Haslund; Christina H Ruhlmann; Lars Bastholt

doi:10.1016/j.ejca.2024.114099

Does patient sex affect the treatment outcome of immune checkpoint inhibitors? A Danish, observational melanoma study

Eur J Cancer. 2024 May 7:205:114099. doi: 10.1016/j.ejca.2024.114099. Online ahead of print.

Authors

Soeren Kjaer Petersen¹, Christian Rønn Hansen², Eva Ellebaek³, Henrik Schmidt⁴, Charlotte Aaquist Haslund⁵, Christina H Ruhlmann⁶, Lars Bastholt⁷

Affiliations

¹ Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern, Denmark. Electronic address: soeren.kjaer@rsyd.dk.
² Department of Clinical Research, University of Southern, Denmark; Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark.
³ National Centre for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
⁴ Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
⁵ Department of Oncology, Aalborg University Hospital, Aalborg, Denmark.
⁶ Department of Oncology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern, Denmark.
⁷ Department of Oncology, Odense University Hospital, Odense, Denmark.

PMID: 38754294
DOI: 10.1016/j.ejca.2024.114099

Abstract

Aim: The objective of this study was to evaluate whether patient biological sex influences treatment outcomes in patients with metastatic melanoma (MM) undergoing first-line immune checkpoint inhibitor (ICI) therapy.

Methods: The Danish Metastatic Melanoma Database (DAMMED) was employed to identify patients who underwent first-line ICI therapy for MM in Denmark from 2013 to 2021. Excluding adjuvant treatment, uveal and mucosal histological subtypes, the study conducted univariable and multivariable analyses to evaluate the influence of patient sex in survival analyses. Further, landmark survival of this real-world national cohort was described for progression free survival (PFS), overall survival (OS) and melanoma-specific survival (MSS).

Results: The analysis encompassed a cohort of 1378 patients with MM. Compared to male sex, females had significantly improved OS (p = 0.003) when tested in univariable testing. Multivariable analyses, controlling for age, performance status, lactate dehydrogenase level, BRAF status, M-stage, and number of metastatic sites revealed significant favourable outcomes associated with female sex irrespective of the considered survival metrics (p_PFS = 0.014, p_OS = 0.002, and p_MSS = 0.03). The observed five-year OS rates of the entire cohort were 47% and 38%, while melanoma-specific survival were 50% and 45% for female and male, respectively.

Conclusion: In this nationwide cohort of patients with MM undergoing first-line ICI treatment females exhibited superior treatment outcomes compared to males. Sex was identified as an independent predictive variable for treatment outcomes, irrespective of the chosen outcome measures considered. Our analyses are not able to conclude whether the differences in outcome is attributable to differences in biology or to treatment strategy.

Keywords: Immune checkpoint inhibitors; Immunotherapy; Improved survival; Metastatic melanoma; Real-world evidence; Sex differences.