PD-L1 expression in muscle invasive urothelial carcinoma: Comparison of SP142 and SP263 assay

Introduction: High-grade urothelial carcinoma has a different molecular pathway than superficial low grade urothelial carcinoma, and is characterized by genomic instability. The high tumor mutation burden leads to neoantigen formation, evoking an immune response. The immune response has been keenly studied in last two decades and programmed death ligand-1 (PDL-1) has emerged as acceptable immunohistochemical marker for assessment of response to therapy, prognostication and patient selection for immunotherapy. The targeting of PD-1 and PDL-1 by checkpoint inhibitors (CPIs) is an attractive strategy to unblock the inhibitor and induce cytotoxic cell death. However, the presence of complementary and companion diagnostic testing with multiple PDL-1 assays and platforms for various CPIs make a diagnostic quagmire. Thus, it is the need of hour to harmonize these assays. In this undertaken study we evaluated the concordance in PD-L1 expression between the two PD-L1 clones: SP263 and SP142, in treatment naïve muscle invasive bladder cancer (MIBC). Methods: We evaluated Ventana PD-L1 “SP263 and SP142” qualitative immunohistochemical assay using rabbit monoclonal anti-PD-L1 clones in evaluation of PDL-1 immunoexpression on Ventana autostainer platform. The study includes 30 muscle invasive urothelial carcinomas, with 10 of 30 having nodal metastasis. Results: SP263 assay was statistically more sensitive than SP142 for tumor cell (TC) scoring (P = 0.0009), whereas SP142 was more sensitive for immune cell (IC) scoring (P = 0.0067). There was no statistical significant discordance for TC or IC scoring between primary tumor and metastatic lymph node. Conclusion: PD-L1 testing status can be done on both primary tumor and metastatic site, however in metachronous metastatic setting, testing on recent metastatic site should be preferred. The harmonization of immunoexpression between 2 PD-L1 clones could not be achieved.

Expression comparison and clinical significance of PD-L1 (22C3) and PD-L1 (SP142) in triple negative breast cancer / 中华肿瘤杂志

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).

Economic evaluation of the SP142 versus 22C3 PD-L1 assays in the treatment of atezolizumab plus nab-paclitaxel for patients with advanced triple negative breast cancer in the Brazilian private healthcare systemp / Avaliação econômica dos testes de PD-L1 SP142 versus 22C3 no tratamento com atezolizumabe mais nab-paclitaxel em pacientes com câncer de mama triplo-negativo avançado no sistema de saúde suplementar no Brasil

Objective: The aim of the study was to demonstrate the economic impact of two PD-L1 immunohistochemistry (IHC) assays, SP142 versus 22C3, in the treatment with atezolizumab plus nab-paclitaxel in patients with advanced triple negative breast cancer (aTNBC) in the Brazilian private healthcare system (BPHS). Methods: The study performed two analyses: one per patient and other of the potential population projected for the BPHS (budget impact analysis). Data of progressionfree survival and overall survival were extracted from a post hoc analysis of the IMpassion130 trial to develop a partitioned-survival model to simulate the economic impact of the treatment with atezolizumab plus nab-paclitaxel guided by the SP142 and 22C3 assays on patients with aTNBC. The analyses included only direct costs that were based on CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) and CMED (Câmara de Regulação do Mercado de Medicamentos) PF18% tables. A univariate sensitivity analysis was performed with the parameters varying ± 20%. Results: The study has demonstrated that the SP142 assay has the potential to save ­BRL 179,730 with the treatment of atezolizumab plus nab-paclitaxel per patient with aTNBC in five years. Conclusion: The SP142 assay can optimize the use of atezolizumab plus nab-paclitaxel avoiding its prescription in patients who will not have a significant clinical improvement.

Objetivo: O objetivo do estudo foi demonstrar o impacto econômico de dois testes de imuno-histoquímica, SP142 versus 22C3, no tratamento com atezolizumabe + nab-paclitaxel em pacientes com câncer de mama triplo-negativo avançado (CMTNa) no sistema de saúde suplementar (SSS) no Brasil. Métodos: O estudo realizou duas análises: uma por paciente e outra na população potencial projetada para o SSS (análise de impacto no orçamento). Dados de sobrevida livre de progressão e de sobrevida global foram extraídos da análise post hoc do estudo IMpassion130 para o desenvolvimento de um modelo de sobrevida particionado que simulasse o impacto econômico do tratamento com atezolizumabe + nab-paclitaxel direcionado pelos testes SP142 e 22C3 em pacientes com CMTNa. A análise considerou somente os custos diretos baseados nas tabelas CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) e CMED (Câmara de Regulação do Mercado de Medicamentos) PF18%. Uma análise de sensibilidade univariada foi realizada variando os parâmetros em ± 20%. Resultados: O estudo demonstrou que o teste SP142 apresenta um potencial de economia de -179.730 reais (BRL) no tratamento de atezolizumabe + nab-paclitaxel por paciente com CMTNa em cinco anos. Conclusão: O uso do teste SP142 possibilita otimizar o uso de atezolizumabe + nab-paclitaxel evitando a sua prescrição em pacientes que não irão se beneficiar de forma significativa.

Comparison of laboratory-developed test & validated assay of programmed death ligand-1 immunohistochemistry in non-small-cell lung carcinoma

Background & objectives: Inhibitors of immune checkpoint regulators, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), improve outcome in advanced non-small-cell lung carcinoma (NSCLC). Tumours expressing PD-L1 protein are more likely to benefit from this targeted therapy. Multiple concurrent clinical trials evaluating different anti-PD-1/PD-L1 therapies have validated five different immunohistochemistry (IHC) assays using varied antibody clones and staining conditions. This study was aimed at identification of a single harmonized PD-L1 assay for tumour tissue conservation and cost-effectiveness in patients with NSCLC. Methods: The performance of low-cost, manual, laboratory-developed technique (LDT) PD-L1 IHC assay using the easily available SP142 clone was compared with trial validated Ventana SP263 IHC performed on automated Ventana staining platform on tumour sections of NSCLCs. Results: Eighty cases of NSCLC were included. SP263 and SP142 stained both tumour cells and immune cells. The concordance rate of tumour cell staining was about 76 per cent, with SP263 detecting more tumour cells in 16 per cent of cases. The concordance rate of immune cell staining was only 61 per cent, with SP142 detecting more immune cells in 24 per cent of cases. The sensitivity, specificity, positive and negative predictive values of manual SP142 LDT assay against gold standard SP263 Ventana assay were 70, 94, 86 and 86 per cent, respectively, at positivity thresholds of ?1 per cent tumour cell staining. Interpretation & conclusions: The study findings suggested that LDT using SP142 clone showed only moderate concordance with SP263 Ventana assay, and the two assays were not interchangeable. More such validation studies need to be done to generate information that can complement patient therapy in cases of NSCLC.