There has been a great deal of excitement surrounding the role of immune checkpoint therapy in NSCLC, particularly with anti-PD-1 and anti-PD-L1 agents. In this regard, recent data indicate that PD-L1 tumor status may be predictive for responses to PD-1- and PD-L1–directed therapies. In a presentation at ASCO 2014, PD-L1 expression was evaluated in a series of adenocarcinomas (AD) and squamous cell carcinomas (SQ) of the lung (Ansen S, et al. ASCO 2014. Abstract 7517). A total of 259 genomically annotated PD-L1+ AD and 180 PD-L1+ SQ tumors were evaluated. For both AD and SQ, no association between PD-L1 positivity and clinical features (gender, smoking history, stage) could be found. PD-L1 expression was not significantly associated with ALK translocation, BRAF mutation, EGFR mutation, TP53 mutation, or RB1 deletion. However, PD-L1 expression in AD was significantly more frequent in KRAS-mutated than in KRAS–wild-type tumors, and less frequent in tumors with STK11 mutations. In SQ, PD-L1 expression was significantly more frequent in tumors with a mutation in exon 2 of NFE2L2. This study showed that PD-L1 expression in the 2 most common NSCLC histologic subtypes is associated with distinct genotypes that may help facilitate identification of patients who are suitable for anti-PD-1 and anti-PD-L1 therapy. However, further refinement and general availability of these genotypic tests are required before they can be used on a regular basis in the clinical setting.
“In order to make the vision of personalized medicine in NSCLC a reality, physicians, pathologists, industry, and regulatory agencies will need to work together.”
