Nivolumab in patients with previously treated advanced NSCLC in clinical practice and correlation with immunological characteristics

Abstract

Background: Non small cell lung cancer (NSCLC) patients with advanced disease who have progressed to a first palliative treatment with platinum-based chemotherapy, have a very poor prognosis; the advent of immunotherapy has begun to change the landscape of the management of this disease, offering a potential for prolonged responses and survival. Nivolumab (Opdivo) was the first programmed death PD-1 immune checkpoint inhibitor to be approved for use in advanced, squamous NSCLC following prior chemotherapy. Material and methods: This is a retrospective review of patients with NSCLC treated with Nivolumab monotherapy (3 mg/Kg/2week) in our centre in compassionate use and in clinical practice. Thirty-six patients were treated between October 2015 to May 2016.We retrospectively evaluated radiological response and clinical benefit; in addition we analyzed the immune status and correlation with lymphocyte subpopulations of each individual patient at baseline and in the course of treatment. Results: All patients were pretreated, 24 (68%) received Nivolumab in 2th line and 12 (34%) in 3th and 4th line; 54% were adenocarcinoma and 48% were squamous histology. Although they have been subjected to chemotherapy and radiotherapy treatment no immune deficiency in the context of lymphocyte subpopulations (CD4-CD8-CD19-CD56) was shown. Imaging response of disease after 4-6 months of treatment could be assesed in 6 patient (35% of squamous histology): 4 patients achieved RP and 2 patients had initial pseudoprogression and later tumor burden reduction or stabilization. The remaining patients still showed a clinical response. The toxicity proved to be in line with the literature data. It was interesting to note that the CD8 value was greater than 500 cell/Ul in all patients in clinical and radiological response. Furthermore, one patient in whom the CD8 was lower than 500 cell/Ul showed a rising trend in the course of the treatment, concomitantly with pseudoprogression and then with RP. Conclusions: Nivolumab has clinically significant activity and manageable safety profile in previously treated patients with advanced refractory NSCLC. Although follow up time was too short to evaluate progression free survival (PFS) and overall survival (OS), the CD8 value may be predictive of response.