Predictive values of peripheral blood biomarkers for atezolizumab in combination with bevacizumab, carboplatin and pemetrexed therapy in EGFR-mutant metastatic non-small cell lung cancer patients

Abstract

Lung cancer is the leading cause of cancer death in 2020. Non-small cell lung cancer (NSCLC), accounts for the majority of lung cancer and is very prevalent around the world. Epidermal growth factor receptor (EGFR) mutation is an important hallmark in NSCLC. As of today, 3 generations of tyrosine kinase inhibitors (TKIs) targeting EGFR have been approved by the United States Food and Drug Administration (FDA) for NSCLC treatment. However, drug resistance due to acquire EGFR mutation will develop eventually and hinder treatment efficacy. Recently, novel immunotherapy drugs such as programmed death-1 (PD-1) blockades and programmed death-ligand 1 (PD-L1) blockades have been approved by the FDA for NSCLC treatment. Despite an improved objective response rate with better safety profile, only a subset of NSCLC patients could benefit from single-agent immunotherapy. A combination of PD-L1 blockade with anti-angiogenetic agent aims to improve treatment response while maintaining a similar adverse event rate. In present study, I have quantified 8 peripheral blood biomarkers from 40 NSCLC patients treated by atezolizumab, bevacizumab, carboplatin and pemetrexed (ABCP). Peripheral blood offers a much less invasive approach to predict treatment response towards immunotherapy. Multiple studies have demonstrated the predictive value of peripheral blood biomarkers towards anti-PD-1 blockades. A significant increase in serum chemokine (C-C motif) ligand 5 (CCL5) level was detected in all patients (p < 0.01). Higher delta change of serum CCL5 level from baseline to week 10’s of treatment was associated with shorter progression-free survival (PFS) (p = 0.001), overall survival (OS) (p = 0.046) and duration of best response (p < 0.001). Furthermore, researchers revealed multiple roles of tumour-derived exosome (TEX) in cancer. Specifically, TEX could modulate anti-tumour immunity and escape immunosurveillance. Therefore, serum exosomal biomarker levels might be useful in cancer diagnosis and treatment monitoring. In present study, serum exosomal PD-L1 level and serum exosomal vascular epidermal growth factor (VEGF) level were significantly elevated after ABCP treatment (p < 0.001). However, these biomarkers were not associated with objective response rate (ORR), PFS, OS or duration of best response. Altogether, quantification of serum and serum exosomal biomarkers from peripheral blood has prognostic value towards ABCP regimen. Early identification of treatment non-responder might allow clinicians and patients to seek alternative therapeutic options and improve survival.