A narrative review of current and potential prognostic biomarkers for immunotherapy in small-cell lung cancer

Abstract

Small-cell lung cancer (SCLC) is a highly invasive and rapidly proliferating pathologic subtype that accounts for 13-15% of all lung cancer cases. Recently in extensive-stage SCLC, treatments that combine immunotherapy and chemotherapy showed increased efficacy compared to chemotherapy alone in several trials. However, the combination of immunotherapy and conventional chemotherapy regimens was introduced only recently for extensive-stage SCLC, with relatively little real-world data. The demand for reliable biomarkers that can predict the efficacy of immunotherapy in SCLC is high. Several studies evaluated various parameters including programmed cell death ligand-1 (PD-L1) expression, tumor mutation burden (TMB), gene expression profiling, autoantibody, and blood cytokines for predictive value for response to immunotherapy in SCLC. Despite some observed correlations, there is a lack of concrete support for the use of PD-L1 expression levels for readily available biomarker. High TMB in combination with smoking history is predictive of a better response to immunotherapy, but validation of cutoffs and testing methods is necessary before it can be widely applied in clinical settings. Other candidate biomarkers such as immune cell distribution among tumor microenvironment, and systemic inflammatory markers can also be evaluated, after an accumulation of real-life data from SCLC patients under immunotherapy.

Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide‐platinum‐atezolizumab treatment

“…Due to the relatively recent introduction of the combination regimen in ES‐SCLC, not many biomarkers were evaluated for use. Although use of immunotherapy is based on PD‐1/PD‐L1 axis, there is no concrete evidence for the use of PD‐L1 expression for immunotherapy in SCLC 16,17 . The combination of high tumor mutational burden (TMB) and smoking history showed a predictive value for better response to immunotherapy 18,19 .…”

“…Although use of immunotherapy is based on PD‐1/PD‐L1 axis, there is no concrete evidence for the use of PD‐L1 expression for immunotherapy in SCLC. 16 , 17 The combination of high tumor mutational burden (TMB) and smoking history showed a predictive value for better response to immunotherapy. 18 , 19 However, TMB requires a validated cutoff to define high versus low, and platform for testing TMB should be more available for practical use as a biomarker.…”

A 2022 Update on Extensive Stage Small-Cell Lung Cancer (SCLC)

“…Also, while the expression of PD-L1, which is generally low in SCLC and not associated with clinical efficacy, unlike in NSCLC, tumor mutation burden (TMB) appears to be more promising with benefit reported for both single-agent nivolumab and the combination of nivolumab and ipilimumab. [62] Currently extensive stage SCLC is treated according to a general, one-size-fits-all paradigm, which may hopefully soon, with new therapies and biomarkers on the horizon, switch to a more precision-based and personalized one.…”

Investigation of poor prognostic factors in extensive-stage small cell lung cancer under etoposide- platinum-atezolizumab treatment

“…Due to relatively recent introduction of the combination regimen in ES-SCLC, not many biomarkers were evaluated for use. Although use of immunotherapy is based on PD-1/PD-L1 axis, there is no concrete evidence for the use of PD-L1 expression for immunotherapy in SCLC 16,17 . Combination of high tumor mutational burden (TMB) and smoking history showed predictive value for better response to immunotherapy 18,19 .…”