Correlation of Neutrophil to Lymphocyte Ratio and Absolute Neutrophil Count With Outcomes With PD-1 Axis Inhibitors in Patients With Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: Programmed death-1 (PD-1) axis inhibitors have become standard therapy in advanced non-small-cell lung cancer (NSCLC). Response might be delayed and pseudo-progression occasionally occurs in patients who eventually benefit from treatment. Additional markers beyond programmed death ligand 1 (PD-L1) expression are needed to assist in patient selection, response evaluation, and treatment decisions. MATERIALS AND METHODS: The relationship between prospectively collected clinical outcomes (response, disease control rate [DCR], treatment duration, overall survival) and hematologic parameters (neutrophil to lymphocyte ratio [NLR], absolute neutrophil count [ANC], and platelet to lymphocyte ratio [PLR]) was explored retrospectively in advanced NSCLC patients treated with PD-1 axis inhibitors at a major cancer center from May 2013 to August 2016. Hematologic parameters at baseline and during treatment (week 2 or 3 and week 8) were included. RESULTS: Of 88 patients treated with PD-1 axis inhibitors, 22 (25%) experienced partial response. Baseline NLR ≤4 was associated with superior DCR (74% vs. 50%; P = .025), treatment duration (P = .037), time to progression (P = .053), and overall survival (P = .019), with no differential association according to PD-L1 tumor expression. Lower NLR and ANC during treatment were also associated with response to treatment (P = .025 and P = .017, respectively), and treatment duration (P = .036 and P = .008). No association was found between baseline PLR and DCR, response, treatment duration, nor overall survival. CONCLUSION: Baseline NLR ≤4 and lower NLR and ANC during treatment might correlate with disease control and treatment response and should be explored further as potential predictors of treatment benefit in larger studies.

Patients with Advanced Non-Small Cell Lung Cancer: Are Research Biopsies a Barrier to Participation in Clinical Trials?

OBJECTIVES: Clinical trials of therapies for non-small cell lung cancer (NSCLC) are increasingly requiring mandatory tumor samples or research biopsies, both of which are potential barriers to trial participation. We assessed the impact of performance of research biopsies on the enrollment of patients with advanced NSCLC in clinical trials. METHODS: The cases of patients with advanced NSCLC who had been evaluated for clinical trials of systemic therapy at the Princess Margaret Cancer Centre from January 2007 to March 2015 were reviewed. RESULTS: Of the 55 clinical trials identified, 38 required tumor samples for enrollment. Six mandated repeat biopsies, whereas 32 permitted use of archival samples. Trial participation was offered to 636 patients at 940 unique study encounters, with some patients enrolling in multiple trials. Of the patients in 549 encounters during which participation in a therapeutic trial was offered, 60% received study treatment. More patients received study treatment (83% versus 55%, p < 0.0001) and study treatment was started earlier (after 9 days versus after 16, p = 0.002) when the trial did not have a mandatory tissue sample requirement. A similar trend was noted for trials permitting use of archival tissue versus mandatory repeat biopsies. The most common barriers to trial enrollment included absence of a required biomarker (34%), withdrawal of consent (20%), deterioration or death (17%), other exclusion criteria (15%), and insufficient biopsy tissue (10%). CONCLUSION: A growing number of NSCLC trials are requiring tumor tissue for treatment eligibility, which appears to be a significant barrier to trial enrollment. Potential solutions include use of available diagnostic samples (e.g., cytology samples), development of peripheral blood assays for molecular markers, faster central laboratory testing turnaround time, and more resources for rapid biopsy.