Prolactin as a Potential Early Predictive Factor in Metastatic Non-Small Cell Lung Cancer Patients Treated with Nivolumab

Abstract

Background/Aims: Prolactin (PRL) is a peptide hormone and several studies have demonstrated its role as a cytokine in human T cell-mediated immunity. We are unaware if PRL is a positive or negative immunomodulator, but its effects on the regulation of T cells could inhibit the antitumor activity elicited by nivolumab (NIVO). We aimed to assess whether the occurrence of hyperprolactinemia in metastatic non-small cell lung cancer (mNSCLC) patients treated with NIVO is associated with poor clinical outcomes. Methods: We evaluated 26 mNSCLC patients treated with NIVO. Blood samples were collected in every patient to evaluate PRL basal levels before starting the therapy with NIVO and before each following administration of NIVO. All patients underwent a conventional CT to investigate the effect of therapy according to Immune-related Response Evaluation Criteria in Solid Tumors (IrRECIST). Results: Twenty patients (77%) developed hyperprolactinemia during the treatment, whereas 6 patients (23%) had stable levels of PRL during the therapy (p = 0.001). A total of 95% of the 20 patients with hyperprolactinemia had progressive disease (PD), according to CT results, whereas only 2 patients (33%) out of 6 with stable PRL levels had PD (p = 0.004). Conclusions: Hyperprolactinemia in mNSCLC patients treated with NIVO could potentially represent a negative early predictive factor for poor clinical outcomes, thus anticipating PD shown by CT scan.

Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors

“…Peripheral cytokines reflect status of tumor immune microenvironment and response to anti-PD-1/PD-L1 treatment [ 93 ]. Prolactin (PRL) participates in maturation and activation of immunity while high PRL inhibits immune response by IL-10 [ 105 ]. Adaptive hyperprolactinemia associates with poor response during nivolumab treatment and patients with stable concentration of PRL exhibit significant higher response rate ( p = 0.004) [ 105 ].…”

“…Prolactin (PRL) participates in maturation and activation of immunity while high PRL inhibits immune response by IL-10 [ 105 ]. Adaptive hyperprolactinemia associates with poor response during nivolumab treatment and patients with stable concentration of PRL exhibit significant higher response rate ( p = 0.004) [ 105 ]. Moreover, a phase 2 study revealed that pretreatment high level of IFN-γ, IL-6, and IL-10 in peripheral blood were relevant to increased objective response rate in melanoma patients receiving nivolumab [ 106 ].…”

Predicting response and toxicity to immune checkpoint inhibitors using routinely available blood and clinical markers

“…Future research will also continue to explore other biomarkers routinely collected in the clinic that may predict response to ICI therapy. Biological plausibility and pilot investigations indicate that performance status, age, concomitant therapy (particularly high-dose corticosteroids), diversity of gut microbiome, prolactin, autoimmune diseases status, human leucocyte antigen class, DNA mismatch repair complex (MMR complex), tumour characteristics (size, location of metastases) and the level of tumour infiltrating lymphocytes are potential markers that should be more thoroughly investigated in the future ( Friedman and Postow, 2016 ; Nishijima et al , 2016 ; Seliger, 2016 ; Topalian et al , 2016 ; Caponnetto et al , 2017 ; Wargo et al , 2017 ; Johnson et al , 2017 ).…”

The Evaluation of Serum Biomarkers for Non-small Cell Lung Cancer (NSCLC) Diagnosis

“…The associations of PRL and development of various cancer has been evaluated in breast, prostate, colorectal, gynecological, and hepatocellular cancer ( Goffin, 2017 ). Only a few studies have examined the relationship between the PRL levels and lung cancer ( Caponnetto et al, 2017 ; Seder et al, 2017 ). PRL was introduced in a seven-analyte panel of lung cancer biomarkers for the first time and the panel was suggested useful to risk stratify cancer patients for early recurrence after resection of node-negative NSCLC less than 4 cm ( Seder et al, 2017 ).…”