Abstract 2614: Decrease of benefit from immune checkpoint inhibitors in women with non-small cell lung cancer
Authors: Pinto Joseph A. , Mas Luis A. , Vallejos Carlos S. , Araujo Jhajaira , Bravo Leny , Aguilar Alfredo , Morante Zaida , Bretel Denisse , Gomez Henry L. , Rolfo Christian 
Published: July 2017

Abstract
Introduction: In a previous work we found differences in immune gene sets enrichment in NSCLC between genders, regardless their smoking status, where women had higher expression of gene sets associated with immune processes. Based in this fact, we hypothesize fewer benefits from immune checkpoint inhibitors in women patients compared than men patients.
Objectives: Evaluate the benefit (in terms of progression-free survival) of women patients from immune checkpoint inhibitors nivolumab and pembrolizumab in published randomized phase III trials.
Methods: We evaluated by meta-analysis four randomized phase III studies, two of prembrolizumab (Herbst et al., 2015 and Reck et al., 2016) and two of nivolumab (Borghaei et al., 2015 and Brahmer et al., 2015). We analyzed TCGA data for lung adenocarcinoma to evaluate differences in the expression of PDCD1, CD274 genes (encoding for PD-1 and PD-L1, respectively).
Results: For all studies, it was observed an overall HR=0.79 (CI95%:0.71-0.87;P&lt;0.00001), although was observed a significant heterogeneity between studies (P=0.002). In male patients, was observed an overall HR=0.71 (CI95%:0.62-0.80;P&lt;0.00001) with significant heterogeneity between studies (P=0.002). For female patients, there was not seen a clear benefit from nivolumab or pembrolizumab (overall HR=0.97, CI95%:0.82-1.14;P=0.67). There was not heterogeneity between the cohorts (P=0.45). There were not differences in the expression of PDCD1 and CD274 genes according to gender in the TCGA data (P=0.371 and 0.144, respectively).
Conclusion: Although there are not differences between genders in the expression of PDCD1 and CD274 genes , such as is previously described for expression for PD-1 and PDL-1 proteins, in our meta-analysis we shown that women have modest benefit from anti immune checkpoint inhibitors. Blockade of PD1 and PD-L1 is a promising therapy in lung cancer; however, a better stratification of patients should be done.
Meta-analysis of four phase III randomized studiesStudyAll patientsMenWomenWeightHazard Ratio IV, Fixed, 95% CIWeightHazard Ratio IV, Fixed, 95% CIWeightIV, Fixed, 95% CIReck et al., 201610.6%0.50 [0.37, 0.68]10.4%0.39 [0.26, 0.581]8.0%0.71[0.40, 1.26Brahmer et al., 201513.7%0.63 [0.48, 0.8217.8%0.63 [0.46, 0.86]11.2%0.75[0.46, 1.22]Borghaei et al., 201530.3%0.91 [0.76, 1.0926.6%0.81 [0.63, 1.04]37.8%1.02[0.78, 1.33]Herbst et al., 201545.40.85 [0.73, 0.98]45.2%0.78 [0.64, 0.95]43.0%1.04[0.81, 1.33]Total (95% Cl)100.0%0.79 [0.71, 0.87]100.0%0.71 [0.62, 0.80100.0%0.97[0.82, 1.14]Heterogeneity: Chi2=14.73,df=3 (P=0.002); I2= 80% Test for overall effect: Z= 4.73 (P &lt;0.00001)Heterogeneity: Chi2=11.12, df=3 (P=0.01); I2=73% Test for overall effect: Z= 5.28 (P&lt;0.00001)Heterogeneity: Ch2=2.67, df=3 (P= 0.45); I2=0% Test for overall effect: Z= 0.42 (P= 0.67)
Citation Format: Joseph A. Pinto, Luis A. Mas, Carlos S. Vallejos, Jhajaira Araujo, Leny Bravo, Alfredo Aguilar, Zaida Morante, Denisse Bretel, Henry L. Gomez, Christian Rolfo. Decrease of benefit from immune checkpoint inhibitors in women with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2614. doi:10.1158/1538-7445.AM2017-2614