The effect of tumor size and metastatic extent on the efficacy of first line pembrolizumab monotherapy in patients with high PD-L1 expressing advanced NSCLC tumors

Abstract

Background: Tumor size and metastatic extent may influence tumor response to immunotherapy in non-small cell lung cancer (NSCLC). The aim of this study was to examine the relationship between both baseline sum of longest diameters (bSLD) and number of metastatic organs (NMO) and the tumor response to pembrolizumab. Secondly, we aimed to analyze the association of baseline SLD and NMO with progression-free survival (PFS) and overall survival (OS). Methods: This retrospective study included patients with high PD-L1 expressing tumors (≥50%) and a good performance score (ECOG ≤ 2) that received first-line pembrolizumab monotherapy. Tumor response was calculated as the 'SLD-change score' and 'early treatment discontinuation' within 3 months on therapy (ETD). The relationship of both bSLD (based on RECIST v1.1) and NMO with tumor response and survival outcome (PFS, OS) was evaluated. Results: No significant differences in SLD-change score could be found using bSLD (OR = 1.010, 95%CI = 0.999-1.021), or using NMO at baseline (OR = 1.608, 95%CI = 0.943-2.743). A bSLD cut-off value of 90 mm was found to be most distinctive for ETD. This cut-off value showed a significant difference for PFS (HR = 2.28, 95%CI = 1.12-4.64, p = 0.023) and OS (HR = 2.99, 95%CI = 1.41-6.34, p = 0.004). NMO also showed a difference for PFS and OS, however, not statistically significant. Conclusions: Tumor size and metastatic extent could not discriminate for tumor response, however, a bSLD of 90 mm could differentiate for PFS and OS.

Organ‐specific responses to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma: A multicentre, retrospective study

“…Notably, patients with large intrahepatic tumours (longest diameter ≥5 cm) had a shorter OS than did those with small intrahepatic tumours, and the OSRR of the liver was lower in patients with large intrahepatic tumours than in those with small tumours. A large baseline tumour size was associated with worse PFS and OS in patients with non‐small cell lung cancer or HCC undergoing treatment with an ICI‐based regimen 15,30–32 . This finding may be partly attributed to baseline tumour size reflecting the fact that higher tumour burden is linked to an inferior prognosis and reduced effectiveness of systemic therapy.…”

“…A large baseline tumour size was associated with worse PFS and OS in patients with non-small cell lung cancer or HCC undergoing treatment with an ICI-based regimen. 15,[30][31][32] This finding may be partly attributed to baseline tumour size reflecting the fact that higher tumour burden is linked to an inferior prognosis and reduced effectiveness of systemic therapy.…”

Two Cases of SMARCA4-Deficient Non-small Cell Lung Cancer (NSCLC) with Improved Performance Status (PS) after Treatment with Immune Checkpoint Inhibitors (ICIs)

“…Predictors of ICI benefit other than PD-L1 expression are pre-treatment tumor size and number of metastases [ 13 ]. In Case 1, there were a total of four distant metastases before treatment with pembrolizumab.…”

Pemetrexed and Platinum Plus Pembrolizumab in Patients With Metastatic Nonsquamous NSCLC by Tumor Burden at Baseline: A Post Hoc Efficacy Analysis of KEYNOTE-189

“…In a recent retrospective real-world analysis of patients with metastatic NSCLC and high PD-L1 expression, baseline tumor burden did not predict response to pembrolizumab. 37 Similarly, Nagasaka et al. 31 reported a lack of association between baseline tumor volume and efficacy outcomes in patients with NSCLC treated with nivolumab or pembrolizumab.…”