Response Rate and Survival at Key Timepoints With PD-1 Blockade vs Chemotherapy in PD-L1 Subgroups: Meta-Analysis of Metastatic NSCLC Trials

Abstract

Background PD-L1 expression (PD-L1) on tumor cells with or without immune cells is widely reported in clinical trials of PD-1 blockade in metastatic non-small cell lung cancer (NSCLC). Various cutpoints have been studied. Methods We performed a systematic search of MEDLINE, EMBASE and conference proceedings up to December 2019 for randomized and non-randomized clinical trials of anti-PD-1 or anti-PD-L1 monotherapy in metastatic NSCLC. We retrieved data on objective response rate (ORR), 1 year (1yr PFS) and 2 year progression-free survival (2yr PFS), and 2 year (2yr OS) and 3 year overall survival (3yr OS) in various PD-L1 subgroups. Results were pooled and analysed based on different cutpoints, with non-randomized comparisons made to pooled chemotherapy outcomes. Results 9,810 patients in twenty-seven studies were included. In treatment-naïve patients, benefits with PD-1 blockade over chemotherapy were seen in ORR in patients having PD-L1 ≥50%, in 2yr OS for PDL1 ≥1%, and in 1yr PFS, 2yr PFS and 3yr OS for unselected patients. First-line PD-1 blockade compared to chemotherapy demonstrated higher ORR, 2yr PFS and 3yr OS if PD-L1 ≥50%; lower ORR, higher 2yr PFS and similar 3yr OS if PD-L1 1-49%; and lower ORR, similar 1yr PFS and lower 2yr OS if PD-L1 <1%. In previously treated patients, PD-1 blockade demonstrated similar or superior outcomes to chemotherapy in all PD-L1 subgroups. Conclusions PD-L1 should guide the choice of PD-1 blockade versus chemotherapy in treatment-naïve patients. In previously treated patients, PD-1 blockade provides a favourable outcome profile to chemotherapy in all PD-L1 subgroups.

Multiparametric Phenotyping of Circulating Tumor Cells for Analysis of Therapeutic Targets, Oncogenic Signaling Pathways and DNA Repair Markers

“…This negative prognostic value of the presence of PD–L1 expressing CTCs after treatment was also shown by Tan et al in a mixed cohort of patients with advanced cancers [ 37 ]. In addition to the accumulating evidence of a positive correlation between baseline PD–L1 positive CTCs and the response to ICI treatment, a negative association with survival after treatment with other non–ICI regimes has been demonstrated in HNSCC [ 36 ] and NSCLC [ 38 ].…”

Brief Report: A Blood-Based MicroRNA Complementary Diagnostic Predicts Immunotherapy Efficacy in Advanced-Stage NSCLC With High Programmed Death-Ligand 1 Expression

“…Currently, both IO and ICT are recommended as treatment options for patients with stage IV NSCLC and PD-L1 TPS greater than or equal to 50%. Nevertheless, the response rate to IO monotherapy is only 40%, 12 and many apparent nonresponders may benefit from ICT, as the chemotherapy component can sensitize the tumor to concurrent immunotherapy. 13 This additional therapeutic burden comes at the cost of increased frequency and severity of toxicity, with grade 3 to 4 adverse events noted in approximately 70% of patients.…”

Development and validation of blood-based predictive biomarkers for response to PD-(L)-1 checkpoint inhibitors: evidence of a universal systemic core of 3D immunogenetic profiling across multiple oncological indications

“…For example, ORR for metastatic NSCLC is 24% and 16%, for treatment-naïve and previously treated patients, respectively [67]. A positive PD-L1 expression result from an immunohistochemistry (IHC) test, which increases ORR to 39.7% (PD-L1 50% or greater) [67] .…”

“…For example, ORR for metastatic NSCLC is 24% and 16%, for treatment-naïve and previously treated patients, respectively [67]. A positive PD-L1 expression result from an immunohistochemistry (IHC) test, which increases ORR to 39.7% (PD-L1 50% or greater) [67] . Many of the remaining patients derive no clinical benefit, suffering significant drug-related adverse events (~14%) or even death from pulmonary toxicity (>1%) [68].…”