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Use of Immune Checkpoint Inhibitors (ICIs) in Patients with Refractory Non-Small Cell Lung Cancer (NSCLC) and Poor Performance Status (PS) World Conference on Lung Cancer 2018





Patients with poor PS generally do not tolerate chemotherapy well, and best supportive care is advocated for patients with Eastern Cooperative Oncology Group (ECOG) PS of 3 or greater. However, immune checkpoint inhibitors (ICIs) are generally better tolerated than conventional chemotherapy, making these drugs attractive options for poor PS patients. Scant literature exists on the safety and efficacy of ICIs in patients with poor PS.


We retrospectively identified patients who received single-agent programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors for refractory NSCLC between January 2015 and December 2017 at our institution. Descriptive tables of patient-, disease-, and treatment-related variables were generated. Overall survival (OS) was stratified by performance status and compared utilizing the Kaplan-Meier method. Multivariable survival analysis was performed using a Cox regression model.


In total, 111 patients received PD-1/PD-L1 inhibitors for refractory NSCLC. PS was 0 in 6 (5%) patients, 1 in 53 (48%) patients, 2 in 37 (33%) patients and 3 in 10 (9%) patients, and 5 patients did not have a recorded PS. Median OS was significantly longer in the PS 0-1 group than the PS 2-3 group (11.3 months vs 4.1 months, p=0.02). Poorer PS (ECOG 2-3) was significantly associated with increased risk for death when controlling for confounding variables (HR 2.1, p=0.004).

Specifically, within the PS 3 group, 2 of 10 patients developed objective responses (1 partial response, 1 complete response). Two patients (20%) had progressive disease. Six patients were non-evaluable for response due to death. The median overall survival was 2.6 months, with the two responding patients both alive over 540 days from initial ICI dose. However, 5 of the 10 patients died within 50 days of initial ICI dose. One of the responding patients developed nivolumab-induced pancreatitis requiring hospitalization, and the other responding patient developed significant, permanent cognitive decline without clear etiology.


This study confirms PS as a strong predictor of OS in refractory NSCLC patients receiving ICIs. Overall, patients with PS 3 suffered poor outcomes with ICIs. However, 2 patients with PS 3 responded to ICI, and both were still alive over 1.5 years from the initial ICI dose. Still, ICI toxicity was common in this population. More experience with PS 2-3 patients should be reported to further evaluate the safety and efficacy of ICIs in this setting. Biomarker-driven selection with high tumor PD-L1 or tumor mutation burden may help improve appropriate utilization of ICIs in this challenging population.

Author List

Jonathan R Thompson, Carlos Arce-Lara, Smitha Menon


Jonathan R. Thompson MD Assistant Professor in the Medicine department at Medical College of Wisconsin
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