PD-L1 Positivity Confers Worse Outcomes in Non–Clear Cell RCC

In patients with non–clear cell renal cell carcinoma (RCC), PD-L1 positivity is associated with worse clinical outcomes, including a shorter overall survival and time to recurrence, according to the results of a study recently published in Annals of Oncology.

“This is the first study to shed light on the role of the PD-1/PD-L1 axis and PD-L1 expression in a group of tumors of the kidney that are uncommon and have no particular standard in the metastatic setting,” said Toni K. Choueiri, MD, of Dana-Farber Cancer Institute in Boston. “Like in clear cell RCC, PD-L1 expression (by immunohistochemistry) seemed to confer a worse outcome.”

According to Choueiri, with all the novel immunotherapies and immune checkpoint inhibitors being tested in clinic and with PD-L1 being a potential promising biomarker for this class of agents, the researchers thought to investigate the role of this biomarker in non–clear cell RCC. This histologic subtype represents 10% to 15% of all RCCs, and patients with this histology usually have been excluded from clinical trials with agents that target the PD-1 and PD-L1 axis.

In the study, the researchers obtained formalin-fixed paraffin-embedded specimens from 101 patients with non–clear cell RCC. Using immunohistochemistry in both the tumor cell membrane and tumor-infiltrating mononuclear cells, they evaluated for PD-L1 expression.

“We found that patients with non–clear cell RCC could express PD-L1 and that different types of non–clear cell RCCs have different levels of expression,” Choueiri told Cancer Network. “Furthermore, expression depends also on the scoring system, which ranges between 11% to 56%, depending on tumor cell membrane vs tumor-infiltrating mononuclear cells.”

Of the 101 patient samples, 10.9% were considered to be positive for PD-L1 when evaluated by tumor cells, including 5.6% of chromophobe RCC, 10% of papillary RCC, 30% of Xp11.2 translocation RCC, and 20% of collecting duct carcinoma. The results showed a significant association between PD-L1 positivity and higher cancer stage (P = .01) and grade (P = .03), as well as a shorter overall survival (P < .001).

In contrast, when evaluating PD-L1 positivity by the tumor-infiltrating mononuclear cells, 56.4% of the patient samples were positive for PD-L1, including 36.1% of chromophobe RCC, 60% of papillary RCC, 90% of Xp11.2 translocation RCC, and 100% of collecting duct carcinoma. Using this evaluation, there was only a trend toward shorter overall survival found in patients who were PD-L1–positive.

Both methods showed an association between PD-L1 positivity and a shorter time to recurrence.

“We found that patients with non–clear cell RCC do express the biomarker of interest for the class of agents that target PD-1 and PD-L1, and also that it seems that the expression is overall associated with poor prognosis,” Choueiri said. “We also feel that excluding these patients from trials of PD-1 inhibitors may be not fully justified if the reason for it is that these tumors lack the marker expression.”