PD-L1 expression in tumors is a candidate molecular marker warranting further investigation as a means to select patients for immunotherapy with an anti PD-1 antibody
John Powderly, MD
PD-L1 expression in tumors is a candidate molecular marker warranting further investigation as a means to select patients for immunotherapy with an anti PD-1 antibody, according to the authors of a 2012 article by Topalian et al1published inThe New England Journal of Medicine, that validated the safety, activity, and immune correlates of the anti-PD-1 antibody nivolumab in several forms of cancer.
In the study, patients with non-small cell lung cancer (NSCLC), melanoma, or kidney cancer whose tumors were PD-L1-positive and who were treated with nivolumab had a 36% objective response rate (ORR). No PD-L1negative tumors responded to the treatment, a finding suggesting that PD-L1 expression on the surface of tumor cells in pretreatment tumor specimens may be associated with ORR, and may be driven by constitutive oncogenic pathways.
Dr. Rizvi on PD-1 and PD-L1 Inhibitors in Lung Cancer
Rizvi is an associate attending physician at Memorial Sloan-Kettering Cancer Center.
However, another explanation for tumor cell expression of PD-L1, the authors suggested, relates to an “adaptive immune resistance in response to an endogenous antitumor immune response,” which may remain in check unless it is unleashed through blockade of the PD-1/PD-L1 pathway.1
Basic questions such as this remain to be answered. But the search for biomarkers of clinical response proceeds in parallel with safety and efficacy investigations of PD-1 pathway inhibitor therapy in advanced solid tumors, specifically melanoma, NSCLC, and renal cell cancer.
N Event/N Subject (%)
Median, months (95% CI)
21.1 (9.4, -)
ORR = objective response rate; OS = overall response; PFS = progression-free survival.
A few of the biomarker investigations that were presented at the 2013 ASCO annual meeting point to more precise matching of patient to therapy: