Programmed Death-ligand 1 Combined Positive Score Research Articles

Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study

AimThe KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab). MethodsThis was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status. ResultsFifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4–83.5) and 96.3% (95% CI 87.3–99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%). ConclusionsSOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer. Trial registrationNCT03382600/JapicCTI-183829.

PD-L1 expression as a prognostic marker in patients with advanced biliary tract cancer.

e16679 Background: Biliary tract cancer (BTC) is associated with poor prognosis because of its aggressive and heterogeneous nature. Programmed death ligand 1 (PD-L1) has been considered as a novel biomarker for prognosis and response of immune checkpoint inhibitors in various tumors. However, there are limited data reporting on the role of PD-L1 in advanced BTC patients. Methods: We analyzed 186 patients with advanced BTC who received palliative gemcitabine and platinum between May 2010 and December 2019. All patients were evaluated for PD-L1 expression by combined positive score (CPS) positivity. Results: In all 186 patients, the median age was 62 years (range 38-82), and the primary tumor location was intrahepatic cholangiocarcinoma (IH-CCC) in 72 patients (38.7%), extrahepatic (EH)-CCC in 90 (48.4%), and gallbladder (GB) cancer in 24 (12.9%). There were 158 (84.9%) patients with recurrent disease and 28 (15.1%) with metastatic disease. Among the 186 patients, 53 (28.5%) had PD-L1 CPS positivity, and 133 were CPS negative. The median overall survival (OS) of patients with PD-L1 CPS positivity or negativity was 12.1 and 15.4 months, respectively. The median progression-free survival (PFS) in patients with PD-L1 positivity or negativity was 5.7 and 7.1 months, respectively. The OS and PFS were not statistically different between groups. In sub-group analysis, EH-CCC patients with PD-L1 negativity had more favorable OS (17.2 vs. 11.6 months, p= 0.002) and PFS (7.8 vs. 5.4 months, p= 0.005) than those that were PD-L1 negative. However, this finding was not reproduced in patients with IH-CCC or GB cancer. Univariate analysis of the association between PD-L1 expression and OS in patients with advanced BTC indicated that PD-L1 CPS positivity has a prognostic role in sub-populations older than 60 years (HR 1.743, CI 1.001-3.034, p = 0.050), those with EH-CCC (HR 2.449, CI 1.355-4.426, p = 0.003), and those with liver metastasis (HR 2.511, CI 1.362-4.626, p = 0.003). Conclusions: This study demonstrated that PD-L1 expression might be a novel prognostic biomarker in patients with EH-CCC but not for patients with IH-CCC or GB cancer.

929P - Biomarker analyses of ramucirumab in patients with platinum refractory urothelial cancer from RANGE, a global, randomized, double-blind, phase III study

BackgroundRANGE previously reported positive progression-free survival1 and a trend towards improved overall survival (OS)2 in ramucirumab (RAM) treated patients. Exploratory biomarker analysis of efficacy by programmed death-ligand 1 (PD-L1) expression revealed a hazard ratio (HR) for OS of 0.519, p=0.0048 in patients with a PD-L1 combined positive score (CPS)≥10 compared to HR of 0.999, p=0.9955 in patients with a PD-L1 CPS<10. We aim to understand prognostic and predictive factors related to survival outcomes in RANGE, and to identify patients who may benefit from RAM therapy using PD-L1 immunohistochemistry and gene expression analysis, defining molecular subtypes, and tumour microenvironment signatures. MethodsArchival tumour specimens that met assay stability requirements (238/530 ITT patients in RANGE) were analyzed with the 22C3 PD-L1 antibody with CPS based on tumour cell (TC) and immune cell (IC) staining. RNA expression analysis on archival tumour tissue (394/530 ITT patients) was done by GenomeDx (RNA microarray)3. PD-L1 groups, urothelial carcinoma molecular subtypes, and immune4 and stromal phenotypes5 were determined and analyzed for association with OS outcome. ResultsOverall, RAM had the greatest improvement in OS in patients with TC≥1, IC≥4 or CPS≥10 PD-L1 status. OS was also more improved in patients with basal subtypes, with considerable overlap noted between basal subtypes and TC≥1, IC≥4, or CPS ≥10 PD-L1 status. In the subgroup with both basal/basal claudin-low subtype and CPS≥10 PD-L1 status, median OS was 9.2 months with RAM and 6.0 months with placebo (stratified hazard ratio 0.47; 95% confidence interval: 0.27-0.84, p=0.01, n=79). ConclusionsOur analysis suggested significant improvement in OS in RAM treated patients with platinum refractory urothelial carcinoma, and with both basal subtype and positive PD-L1 status.

990TiP - Phase III LEAP-011 trial: First-line pembrolizumab with lenvatinib in patients with advanced urothelial carcinoma ineligible to receive platinum-based chemotherapy

990TiP - Phase III LEAP-011 trial: First-line pembrolizumab with lenvatinib in patients with advanced urothelial carcinoma ineligible to receive platinum-based chemotherapy