Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012.

Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma

“…The investigators showed the anti-PD-1 antibody pembrolizumab has significant efficacy in patients with advanced gastric cancer (NCT01848834). 44 Only patients with distinctive stromal or ≥1% tumour cell PD-L1 staining (22C3 antibody) were eligible. Of the 162 patients screened, 65 (40%) were considered PD-L1 + .…”

The development of immunotherapy in older adults: New treatments, new toxicities?

“…Indeed, ICBs have been approved for patients with melanoma, non-small cell lung cancer, and renal cell cancer. [3][4][5][6][7][8] Clinical indications of immunotherapeutic agents are expected to increase as clinical responses with ICB are observed in many different cancer subtypes: small cell lung cancer (15% ORR), 9 urothelial cancer (25% ORR), 10 head and neck squamous cell carcinoma (12-25% ORR), 11,12 gastric cancer (20% ORR), 13 hepatocellular carcinoma (20% ORR), 14 ovarian cancer (15% ORR), 15,16 triple negative breast cancer (20% ORR), 17 mismatch repair deficient colorectal cancer (60% ORR) 18 and Hodgkin lymphoma (65-85% ORR). 19,20 Moreover, ICB monotherapy studies have shown a good safety profile with~10% of severe toxicities.…”

Personalizing the Management of Gastroesophageal Cancer

“…As gastroesophageal cancer shares a high mutational load with melanoma and NSCLC, it is hoped that these patients may also benefit from activation of the immune system using immune checkpoint inhibitory therapies [39]. Recent data have demonstrated response rates of approximately 20% gastric cancer patients who were PDL1 positive (at a threshold of 1%) treated with pembrolizumab [24]. As the studies so far presented have selected only PDL1-positive patients (~40% of all patients screened), it is not known whether such therapies could benefit PDL1-negative patients, and more work is required to accurately define the use of this biomarker, and also to assess whether gene expression profiles predictive of benefit in melanoma are predictive across tumor types [40].…”

“…Trial design for low prevalence biomarker populations: thinking ahead As a roadmap for personalized therapy and clinical trial design, the TGCA shows promise: EBV-positive tumors display high rates (up to 80%) of PIK3CA mutations and are enriched for amplifications in PD-L1 and PD-L2 which may act as potential targets for novel immunotherapies, in particular those which have recently demonstrated encouraging early efficacy this disease [24,25]. Pathway analysis confirmed evidence of increased immune-related signaling in these tumors providing further support for this approach for EBVpositive patients.…”