PD-L1 and Lung Cancer: The Era of Precision-ish Medicine?

Area of Science:

• Oncology
• Immunotherapy
• Pathology
• Diagnostic Testing

Background:

• Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in treating both squamous and nonsquamous non-small cell lung carcinoma.
• This success has resulted in FDA approval of medications accompanied by immunohistochemistry (IHC)-based companion or complementary diagnostic tests for programmed death ligand-1 (PD-L1).

Purpose of the Study:

• To discuss the challenges in precision medicine posed by the proliferation of diverse IHC-based PD-L1 tests.
• To highlight the difficulties faced by pathologists and oncologists in optimizing patient care within this complex therapeutic landscape.

Main Methods:

• Review of current landscape of ICI therapy in lung cancer.
• Analysis of the implications of various IHC antibodies, instruments, and scoring systems for PD-L1 testing.
• Discussion of the paradigm shift from paired molecular target/test to multiple diagnostic approaches.

Main Results:

• The success of ICIs in lung cancer is linked to PD-L1 diagnostic tests.
• A growing number of ICI agents with associated diagnostics are emerging.
• The proliferation of IHC tests with varying methodologies presents challenges to standardized interpretation and application.

Conclusions:

• The era of precision medicine in lung cancer is complicated by the heterogeneity of PD-L1 IHC assays.
• Pathologists and oncologists face significant challenges in selecting appropriate tests and interpreting results to guide ICI therapy.
• Further standardization and validation of diagnostic tests are crucial for optimizing patient outcomes in ICI treatment.