Immunotherapy in Small Cell Lung Cancer

Abstract

Small-cell lung cancer (SCLC) is an aggressive tumor type with limited therapeutic options and poor prognosis. Chemotherapy regimens containing platinum represent the cornerstone of treatment for patients with extensive disease, but there has been no real progress for 30 years. The evidence that SCLC is characterized by a high mutational burden led to the development of immune-checkpoint inhibitors as single agents or in combination with chemotherapy. Randomized phase III trials demonstrated that the combination of atezolizumab (IMpower-133) or durvalumab (CASPIAN) with platinum-etoposide chemotherapy improved overall survival of patients with extensive disease. Instead, the KEYNOTE-604 study demonstrated that the addition of pembrolizumab to chemotherapy failed to significantly improve overall survival, but it prolonged progression-free survival. The safety profile of these combinations was similar with the known safety profiles of all single agents and no new adverse events were observed. Nivolumab and pembrolizumab single agents showed anti-tumor activity and acceptable safety profile in Checkmate 032 and KEYNOTE 028/158 trials, respectively, in patients with SCLC after platinum-based therapy and at least one prior line of therapy. Future challenges are the identification predictive biomarkers of response to immunotherapy in SCLC and the definition of the role of immunotherapy in patients with limited stage SCLC, in combination with radiotherapy or with other biological agents.

Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

“…On the other hand, first-line treatment in patients with ED-SCLC is undergoing great changes, especially in the field of immunotherapy. For example, blocking the programmed death 1 receptor (PD-1) or its ligand (PD-L1) pathway has been shown to improve the prognosis of patients with ED-SCLC [ 18 , 19 ]. The Impower 133 (NCT02763579) and CASPIAN phase III trials (NCT03043872) demonstrated that adding atezolizumab or durvalumab to platinum plus etoposide chemotherapy improves OS and progression-free survival (PFS) compared to chemotherapy alone [ 20 , 21 ].…”

Immune Check Point Inhibitors and Immune-Related Adverse Events in Small Cell Lung Cancer

“…The prognosis of patients with LS-SCLC is better than those with ES-SCLC, the survival time of patients with LS-SCLC ranges from 15 to 20 months and their 5-year survival rate is ~20–25%. In comparison, the survival time of patients with ES-SCLC ranges from 8 to 13 months, with a 5-year survival rate of only about 2% ( 3 , 4 ). Unfortunately, ~70% of SCLC patients are diagnosed with ES-SCLC ( 5 ).…”

Cancer Immunotherapy Update: FDA-Approved Checkpoint Inhibitors and Companion Diagnostics

“…An improved overall survival rate was seen in patients with high PD-L1 expression (16,17). Not all lung cancer indications require a PD-L1 protein measurement, including the first-line treatment of patients with squamous or non-squamous NSCLC as a single agent or in combination with carboplatin and either paclitaxel or nabpaclitaxel (18,19) or patients with SCLC with disease progression on or after platinum-based chemotherapy, and at least one other prior line of therapy (20,21). In these clinical studies, patients demonstrated benefit regardless of the level of PD-L1 expression.…”