Publication details

Sex and survival outcomes in patients with renal cell carcinoma receiving first-line immune-based combinations

Authors	INCORVAIA Lorena MONTEIRO Fernando Sabino Marques MASSARI Francesco PARK Se Hoon ROVIELLO Giandomenico FIALA Ondrej MYINT Zin W KUCHARZ Jakub MOLINA-CERRILLO Javier SANTINI Daniele BUTTNER Thomas POPRACH Alexandr KOPECKY Jindrich ZEPPELLINI Annalisa PICHLER Martin BUCHLER Tomas PICHLER Renate FACCHINI Gaetano FAY Andre Poisl SOARES Andrey MANNEH Ray IEZZI Laura KURONYA Zsofia RUSSO Antonio BOURLON Maria T BHUVA Dipen ANSARI Jawaher KANESVARAN Ravindran GRANDE Enrique BUTI Sebastiano SANTONI Matteo
Year of publication	2024
Type	Article in Periodical
Magazine / Source	Cancer immunology, immunotherapy
MU Faculty or unit	Faculty of Medicine
Citation
Web	https://link.springer.com/article/10.1007/s00262-024-03719-0
Doi	http://dx.doi.org/10.1007/s00262-024-03719-0
Keywords	ARON-1 study; Gender differences; Immunotherapy; Immune-based combinations; NCT05287464; Renal cell carcinoma
Description	Background There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking. Method This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy. Results A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008). Conclusions Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.