Tumor Response Dynamics of Advanced Non-small Cell Lung Cancer Patients Treated with PD-1 Inhibitors: Imaging Markers for Treatment Outcome

• Published in: Clinical cancer research Vol. 23; no. 19; pp. 5737 - 5744
• Main Authors: Nishino, Mizuki, Dahlberg, Suzanne E, Adeni, Anika E, Lydon, Christine A, Hatabu, Hiroto, Jänne, Pasi A, Hodi, F Stephen, Awad, Mark M
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 01-10-2017
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Biomarkers, Tumor - genetics; Cancer; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Disease control; Disease Progression; Disease-Free Survival; Erlotinib Hydrochloride - administration & dosage; Erlotinib Hydrochloride - adverse effects; Experimental design; Female; Hazards; Humans; Inhibitors; Kaplan-Meier Estimate; Lung cancer; Male; Markers; Middle Aged; Monoclonal antibodies; Non-small cell lung carcinoma; Patients; PD-1 protein; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - genetics; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - immunology; Smoking; Targeted cancer therapy; Therapy; Treatment Outcome; Tumor Burden - genetics
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-17-1434

We evaluated tumor burden dynamics in patients with advanced non-small cell lung cancer (NSCLC) treated with commercial PD-1 inhibitors to identify imaging markers associated with improved overall survival (OS).
The study included 160 patients with advanced NSCLC treated with commercial nivolumab or pembrolizumab monotherapy as a part of clinical care. Tumor burden dynamics were studied for the association with OS.
Tumor burden change at best overall response (BOR) ranged from -100% to +278% (median, +3.5%). Response rate (RR) was 18% (29/160). Current and former smokers had a higher RR than never smokers (
= 0.04). Durable disease control for at least 6 months was noted in 26 patients (16%), which included 10 patients with stable disease as BOR. Using a landmark analysis, patients with <20% tumor burden increase from baseline within 8 weeks of therapy had longer OS than patients with ≥20% increase (median OS, 12.4 vs. 4.6 months,
< 0.001). Patients with <20% tumor burden increase throughout therapy had significantly reduced hazards of death (HR, 0.24; Cox
< 0.0001) after adjusting for smoking (HR, 0.86;
= 0.61) and baseline tumor burden (HR, 1.55;
= 0.062), even though some patients met criteria for RECIST progression while on therapy. One patient (0.6%) had atypical response pattern consistent with pseudoprogression.
Objective response or durable disease control was noted in 24% of patients with advanced NSCLC treated with commercial PD-1 inhibitors. A tumor burden increase of <20% from baseline during therapy was associated with longer OS, proposing a practical marker of treatment benefit. Pseudoprogression is rare in NSCLCs treated with PD-1 inhibitors.
.