Targeted therapies have potential for sarcomatoid lung carcinomas

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Sarcomatoid carcinomas may benefit from therapies targeting programmed death-1 (PD-1) protein and programmed death ligand-1 (PD-L1). PD-1 protein occurs in sarcomatoid carcinomas at higher levels than in other non-small cell lung cancers (NSCLC).

Sarcomatoid carcinomas of the lung include rare subtypes of poorly differentiated NSCLC of high grade and aggressive behavior. The biology of these neoplasms is poorly understood. These tumors are aggressive and resistant to chemotherapy. Identifying actionable molecular targets for such infrequent and aggressive diseases is critical to designing clinical trials that will yield the most valid and useful results.

PD-1 is a coinhibitory inducible receptor present on T cells and macrophages. Tumor cells with increased PD-L1 are believed to escape immunity by activating the PD-1/PD-L1 pathway and suppressing effector-immune responses.

Promising results have come from recent strategies that target the PD-1/PD-L1 axis in tumor types that include lung carcinomas. The expression of PD-L1 protein may predict response to such therapies.

The research team from Yale University in New Haven, Connecticut, measured the levels of the PD-L1 protein in sarcomatoid carcinomas. They found that sarcomatoid carcinomas have higher PD-L1 levels than NSCLC, which supports the potential use of anti-PD-1/PD-L1 targeted therapies. Their study was published in the Journal of Thoracic Oncology (2013; doi: 10.1097/JTO.0b013e318292be18).

This analysis from two large retrospective lung cancer cohorts found that 9 of 13 patients (69.2%) with sarcomatoid carcinomas were positive for PD-L1. Their levels of PD-L1 were higher than those in patients with conventional NSCLC. These higher levels provide a rationale for the potential of targeted immunotherapy in lung sarcomatoid carcinomas.

The study said, "despite the presence of rich inflammatory infiltrates patients with sarcomatoid carcinomas have worse outcomes compared with other histologic subtypes of NSCLC. Elevated expression of PD-L1 by sarcomatoid carcinoma cells might account for this apparent contradiction because local inactivation of effector-immune cells through PD-1 receptor signaling could ultimately enhance the disease progression." The researchers, "suggest the possibility of using novel immunotherapy approaches such as PD-1/PD-L1 blockers in this otherwise difficult to treat disease."

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