Background: Nivolumab and pembrolizumab, two programmed death (PD)-1 immune-checkpointeinhibitor antibodies, demonstrated superiority versus standard chemotherapy in second- third line in both squamous and non-squamous lung cancer. Large cell neuroendocrine lung cancer (LCNEC) is a rare tumour often treated as a small cell lung cancer, but there is not a standard of care after a first line progression. Aim of the study was to assess clinical efficacy of PD-1 inhibitors in these patients. Methods: We retrospectively reviewed all consecutive LCNEC stage IIIB- IV patients treated with nivolumab or pembrolizumab after platinum-based first line therapy between July 2014 and November 2015 in six French centers. Patients were followed until June 2016. The drugs were given in an early access program or a clinical trial. Results: The analysis included 10 patients with advanced stage disease. Eight patients (80%) had a stage IV disease with a median age of 59 [interquartile range (IQR) 55-62] years. The majority were males (n=9; 90%), with good performance status (0-1; 9/90%) and 50% were treated in third line or further. Three patients presented brain metastases. In 5 cases a molecular test was done, finding in one case (20%) a KRAS mutation. Patients received a first line treatment with platinum and etoposide in 8 cases (80%) with a disease control rate of 50%. Nine patients received nivolumab and the PD-L1 status was never performed, while the patient treated with pembrolizumab expressed PD-L1. Patients received a median number of 16 [IQR, 13-18] cycles, 6 showed a partial response (60%), 1 a stable disease (10%). Median PFS was 57 [24-57] weeks. Most of the patients stopped treatment due to disease progression (n=4; 80%), only one for a pulmonary interstitial pneumonia. Conclusion: Our findings suggest that the use of immune- checkpointeinhibitors in LCNEC could be explored in a larger cohort of patients. This treatment could be considered in the scenario of a disease with limited therapeutic strategy.
Levra, M. G., Mazieres, J., Valette, C. A., Molinier, O., Planchard, D., Frappat, V., … Moro-Sibilot, D. (2017). P1.07-012 Efficacy of Immune Checkpoint Inhibitors in Large Cell Neuroendocrine Lung Cancer: Results from a French Retrospective Cohort. Journal of Thoracic Oncology, 12(1), S702–S703. https://doi.org/10.1016/j.jtho.2016.11.923