The impact of pre-treatment plasma sex hormones on the immune checkpoint inhibitors response to metastatic non-small cell lung cancer.

Abstract

e21088 Background: Immune checkpoint inhibitors (ICI) have changed the outcomes in metastatic non-small cell lung cancer (mNSCLC). The immune system partially determines the response to ICI. The impact of sex hormones on immune responses is well recognized in autoimmune disease and vaccine response. Little is known about the interplay between the sex hormones and the response to ICI in mNSCLC. Methods: This prospective, observational study included patients with mNSCLC at Moffitt Cancer Center who received ICI as monotherapy or combination with chemotherapy. Plasma was collected before the first ICI infusion. Extraction and detection of the hormones were optimized by modifying the previous method. Hormone levels were measured using ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Estrogens included propyl pyrazole triol (PPT), 17β-estradiol (E2), and S-equol. Androgens included 5-androstenediol, 3β-androstenediol (3β-diol), and dehydroepiandrosterone (DHEA).Patients were divided based on clinical benefits, defined as a complete or partial response or stable disease for at least 12 months. Categorical variables were compared using the Chi-square test or Fischer exact test; continuous variables were compared using the Mann-Whitney U test. Results: Sixty-one patients were included and 50.8% were female. The median age was 67 years. Twenty-eight patients had clinical benefits from ICI. Patients in the clinical benefit group had higher BMI. The clinical benefit group had significantly lower androgen levels but no difference in estrogen levels. The median DHEA level was 3.7 ng/ml in the clinical benefit group and 9.6 ng/ml in the group without (p < 0.001). The 5-Androstenediol was also lower in the clinical benefits group (table I). When normalized to the age/sex-adjusted reference range, the difference of DHEA and 5-androstenediol was retained (p < 0.001 and 0.014, respectively). 3β-diol was below the limit of detection. Conclusions: The serum DHEA and 5-androstenediol levels were lower in mNSCLC patients who benefited from ICI, regardless of sex. Larger studies are needed to confirm the role of pre-treatment androgens levels as negative biomarkers for ICI response. [Table: see text]