Prolactin as a potential negative predictive factor in metastatic non-small cell lung cancers (NSCLC) patients in treatment with Nivolumab (NIVO)

Abstract

Background: Prolactin (PRL) is a peptide hormone secreted by the anterior pituitary gland. Several studies have demonstrated the role of PRL as a cytokine in human T cell-mediated immunity. T-cells secrete PRL and express on their surface the receptor for prolactin (PRL-R). The interaction of PRL with PRL-R leads to an intracellular cascade mediated by Jak2/Stat5 which regulates T cells activation. Although it is still unclear if PRL is a positive or negative immune-modulator, its effects on T cells regulation could inhibit the antitumor activity elicited by NIVO through immune checkpoint blockade. As a result, we decide to evaluate whether occurrence of hyperprolactinemia in NSCLC patients in treatment with NIVO is associated with poor clinical outcomes. Methods:We conducted a retrospective study on 26 NSCLC patients treated with NIVO, for whom PRL, TSH and ACTH levels prior and during NIVO treatment were available. Firstly, blood samples were collected in every patient to evaluate basal hormones levels before starting the therapy with NIVO. The same procedure was repeated before each following administration of NIVO as well. After completing the whole treatment, all patients underwent conventional CT to investigate the effect of therapy according to RECIST criteria. Results: 26 NSCLC patients with normal PRL, TSH and ACTH levels before treatment, received NIVO until the CT evaluation. 18 patients (69%) developed hyperprolactinemia during the therapy whereas 8 patients (31%) had stable levels of PRL during the entire treatment (p = 0,001). No symptoms caused by hyperprolactinemia were reported in patients. 100% of the 18 patients with hyperprolactinemia had a progressive disease (PD) according CT results, whereas only 1 patient (12,1%) out of 8 with stable PRL levels had a PD (p = 0,03). Conclusions: If validated prospectively, the occurrence of hyperprolactinemia in NSCLC patients in treatment with NIVO could potentially represent a negative predictive factor for poor clinical outcomes anticipating the PD showed by imaging tests in patients.