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

Abstract

The success of immune checkpoint inhibitor therapy in lung cancer, both in squamous and nonsquamous non–small cell carcinoma, has led to US Food and Drug Administration approval for 2 medications that have as part of their prescribing information an associated immunohistochemistry-based companion or complementary diagnostic test for programmed death ligand-1 (PD-L1). The intense interest in drug development in this area has resulted in additional agents with associated diagnostics looming on the horizon in 2016. In the era of precision medicine, the paradigm of paired molecular target and molecular test, which serves as a model of oncogenic mutation-driven cancer therapy, is challenged by the proliferation of immunohistochemistry-based tests with different antibodies, instruments, and scoring. The difficulty inherent to targeted therapy aimed at a moving target is discussed, as well as the emerging challenges to pathologists and oncologists who seek to optimize care in this complex therapeutic arena.

Comparison of continuous measures across diagnostic PD-L1 assays in non-small cell lung cancer using automated image analysis

“…Response rates to anti-PD-1 and anti-PD-L1 agents have been shown to be greater in patients whose tumors express high levels of PD-L1 compared with those expressing low or no tumor PD-L1 [1][2][3][4]. Broad access to high-quality PD-L1 testing will help clinicians to identify the most appropriate treatment option for individual patients.…”

“…Tumors can evade the immune system via exploitation of inhibitory checkpoint pathways that suppress antitumor T-cell responses [1]. In the programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) pathway, the PD-L1 expressed by tumor or tumor-infiltrating immune cells binds to PD-1, inhibiting T-cell receptor signaling and blocking antitumor immune response [2][3][4]. Antibodies targeting PD-1 or PD-L1 can block this interaction, thus resuming antitumor response [2].…”

Agreement between Programmed Cell Death Ligand-1 Diagnostic Assays across Multiple Protein Expression Cutoffs in Non–Small Cell Lung Cancer

“…Among the most important of these checkpoints is the programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) pathway, in which PD-L1 expressed by tumor or tumor-infiltrating immune cells binds to PD-1, inhibiting T-cell receptor signaling and blocking the antitumor immune response (2)(3)(4). Blocking antibodies that target PD-1 or PD-L1 have been developed to interrupt this interaction (2), and a number of effective therapeutics are emerging in multiple tumor types, including non-small cell lung cancer (NSCLC; refs. 3,4).…”

Genomics: the clinical encounter and parallels across complementary and personalized medicine

“…We argue that each cannot be seen as distinct, nor should the translation of genetic research into PPM be simply considered a “top‐down” process. We have illustrated that the process of converting genetic research (laboratory) into PPM (clinic) is “precision‐ish” (Borczuk & Allen, , p. 354): a messy, back and forth process of financially, disciplinary, and temporally constrained negotiation and culturally informed knowledge transfer that embeds individuals (patients) and their genetically related family. The involvement of individuals and their families in PPM, including their narratives and life circumstances, has the potential to change what counts as “evidence,” and highlights the contributions of stakeholders beyond the research‐healthcare nexus (Prainsack, ).…”