ABSTRACT J‐TAIL‐2 evaluated the efficacy and safety of atezolizumab, an anti–programmed death‐ligand 1 (PD‐L1), plus chemotherapy in patients with non‐small cell lung cancer (NSCLC) and extensive‐stage small cell lung cancer (ES‐SCLC) in Japanese clinical practice, demonstrating comparable outcomes to those in the corresponding Phase 3 trials. Although PD‐L1 expression is predictive of atezolizumab efficacy in some settings, additional minimally invasive, blood‐based biomarkers are needed. This exploratory biomarker study included 359 J‐TAIL‐2 patients. The NSCLC cohort received atezolizumab combined with carboplatin and nab‐paclitaxel (CnP, n = 42), cisplatin/carboplatin and pemetrexed ( n = 72), or bevacizumab plus carboplatin and paclitaxel (bev + CP, n = 135). The ES‐SCLC cohort received atezolizumab plus carboplatin and etoposide ( n = 100). Approximately 560 cancer‐ or immune‐related proteins were evaluated using the Proximity Extension Assay from blood plasma collected at three timepoints: baseline, before the second atezolizumab dose, and at the onset of immune‐related adverse events (irAEs). Protein‐wise comparisons were made to evaluate significant changes ( P 0.5 log2 fold change) and linked to clinical outcomes reported in J‐TAIL‐2. IL‐6, MUC‐16, and KRT‐19 were associated with shorter progression‐free survival across multiple regimens. Granzyme A and B, immune activation markers, were elevated in responders who received atezolizumab + CnP and atezolizumab + bev + CP. High levels of baseline immune stimulation proteins were associated with irAEs across regimens. Protein expression changes were varied and regimen‐dependent in subgroup analyses including older patients and those with EGFR ‐mutant tumors. These data warrant further investigation across different cancer types and atezolizumab‐containing regimens to determine their relevance to efficacy and irAE occurrence of atezolizumab combination therapy. Trial Registration: ClinicalTrials.gov ID, NCT04501497 (J‐TAIL‐2) and NCT04818983 (biomarker study)
Goto et al. (Tue,) studied this question.