Network Meta-analysis Comparing Efficacy, Safety and Tolerability of Anti-PD-1/PD-L1 Antibodies in Solid Cancers

Abstract

Background: Multiple anti-PD-1/PD-L1 antibodies have been approved, and in some diseases, there is a choice of more than one. Comparative efficacy, safety and tolerability are unknown. Methods: Randomized trials (RCTs) supporting the registration of single agent anti-PD1 or anti-PDL1 inhibitors between 2015-2019 were identified. We extracted the hazard ratio (HR) for overall survival (OS) and calculated the odds ratio (OR) for commonly reported safety and tolerability outcomes. We then performed a network meta-analysis, reporting multiple pair-wise comparisons between different anti-PD-1/PD-L1 antibodies. Results: Sixteen RCTs comprising 10673 patients were included; 10 in non-small-cell lung cancer, 2 in melanoma, 2 in head and neck squamous cell carcinoma and 2 in urothelial cancer. Compared to pembrolizumab, efficacy was similar for nivolumab (HR: 1.02 95% CI: 0.91-1.14) and for atezolizumab (HR: 0.97 95% CI: 0.85-1.10), however, avelumab appeared inferior (HR: 1.30, 95% CI: 1.06-1.56). Pembrolizumab showed similar odds of serious adverse events (SAEs) as nivolumab (OR: 1.12, 95% CI: 0.56-2.27) and atezolizumab (OR: 1.05, 95%

Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types

“…Due to the retrospective nature of the study, we were unable to systematically control for heterogeneity in patient treatment regimens and other potential confounders. For instance, although previous reports have not clearly shown a significant difference in efficacy between different ICI agents, [45][46][47] we could not entirely exclude the possibility of confounding of ICI response rates by the specific ICI regimen used. In addition, the limited number of patients in the current data set for whom ancillary biomarker status was available (MSI, PD-L1 and TMB) precluded more sophisticated analyses of the relationship between these biomarkers and the AI-based immune phenotype.…”

Selection of a PD‐1 blocking antibody from a novel fully human phage display library

“…Immune checkpoint inhibitors are increasingly being used for the immunotherapy of cancer, providing an objective benefit to patients with different types of malignancies. 2,3,17,38,39 The use of monoclonal antibodies, capable of blocking the interaction of PD-1 with its cognate PD-L1 and PD-L2 ligands, has received marketing authorization for the treatment of melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma and various other indications. 14,[40][41][42][43][44][45] This work describes the isolation and in vitro characterization of a new anti-PD-1 antibody (D12), isolated from a synthetic phage display library termed AMG.…”

Factores pronósticos de la supervivencia en pacientes con melanoma de piel metastásico, que reciben primera línea de tratamiento con inmunoterapia anti PD-1 o régimen con anti PD-1 y anti CTLA-4, en el Instituto Nacional de Cancerología de Colombia

“…Por otro lado, fue sorprendente la diferencia de resultados entre las dos terapias anti-PD1, ya que si bien no hay ensayos clínicos aleatorizados que los comparen directamente, sí se han realizado comparaciones indirectas en estudios retrospectivos y en metaanálisis en red, sin encontrar diferencias en eficacia ni seguridad entre los dos medicamentos (41). Una hipótesis para esta diferencia podría ser que ante el intervalo de dosis mayor con pembrolizumab (dosis cada 3 o 6 semanas) vs. nivolumab (dosis cada 2 o 4 semanas) se formulase el primero en pacientes más enfermos, mayores o con problemas de acceso, lo que se reflejaría en un peor desenlace.…”