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Standard of care for Extensive-Stage Disease (ED) Small
Cell Lung Cancer (SCLC) as first-line treatment is 4 to 6
cycles of platinum based chemotherapy (carboplatin or
cisplatin) in combination with etoposide. However, the
outcome of the disease remains poor with a median overall
survival of approximately 10 months, mainly caused
by rapid development of drug resistance. The risk of intrathoracic
recurrences can be reduced and an improved
2-year survival can be achieved with the addition of thoracic
radiotherapy (tRT).
tRT is thought to exert direct cytotoxic effects on tumor
cells, but also reprograms the tumor microenvironment to
exert a potent antitumor immune response and enhances
antitumor immunity. tRT initiates immunogenic cell death,
causing production and release of the cytokines and
chemokines into the tumor microenvironment. This
causes chemoattraction and infiltration of dendritic cells to
the site of the tumor. Activation of dendritic cells, which
are essential antigen presenting cells and up-regulation of
cytotoxic T-regulatory cells (Tcells) are responsible for the
abscopal effect mechanism, i.e. (systemic) anti-tumor immune
response within the body.
The aim of the SAKK 15/19 trial is to counteract this effect,
by combining the high-affinity, engineered human immunoglobulin
G1 kappa (IgGlic) monoclonal antibody,
durvalumab, with tRT. Durvalumab is thought to induce
antibody-dependent cell-mediated cytotoxicity and complement-
dependent cytotoxicity, thereby activating the immune
system to attack the tumor cells and increase the
abscopal effect.