Immunotherapy in extensive small cell lung cancer

Abstract

Small cell lung cancer which constitutes about 15% of lung cancers is pathobiologically and clinically distinct from non small cell cancer. Histologically it is characterized by small cells with scant cytoplasm, absent or inconspicuous nucleoli, extensive necrosis, and expresses neuroendocrine markers. It is on a spectrum of neuroendocrine cancer that extend from typical carcinoids to large cell to small cell cancer. Clinically it behaves in a more malignant fashion with a rapid doubling time, early metastasis. They respond rapidly to cytotoxic treatment however tend to develop resistance soon. Immunotherapy with checkpoint inhibitors take advantage of PD 1 ligand-receptor axis between the tumor and T cells or CTLA4 on T cells which when engaged lead to inhibition of T cells. This inhibition helps tumors to evade immune surveillance. Checkpoint inhibitors break this axis by either binding to PD 1 ligands or PD 1 to CTLA4, thereby preventing tumors to evade the immune systems. This has led to remarkable responses in tumors. The immune related adverse effects can be severe however are experienced at much lower rates as compared to cytotoxic chemotherapy. Recently, CheckMate 032 has shown impressive response rates with Nivolumab and Nivolumab/Ipilimumab in relapsed small cell cancer. IMpower 133, a phase 3 trial showed that addition of Atezolizumab to Carbo/Etoposide led to a significant survival benefit in treatment naive extensive small cell cancer. This review will summarize recent developments and ongoing studies of immune therapy in extensive small cell cancer in addition to a brief summary of immune therapy landscape of Non small cell lung cancer. Investigational approaches to immune therapy have also been delineated.