Lack of Association Between Radiographic Tumor Burden and Efficacy of Immune Checkpoint Inhibitors in Advanced Lung Cancer. (31st March 2020)

• Record Type: Journal Article
• Authors: Popat, Vinita; Lu, Rong; Ahmed, Murtaza; Park, Jason Y.; Xie, Yang; Gerber, David E.
• Is Part Of: Oncologist. Volume 25:Number 6(2020)
• Page Start: 515
• Page End: 522
• Publication Date: 2020-03-31
• Subjects: Lung cancer -- Imaging -- Immunotherapy -- Outcomes -- RECIST -- Burden; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2019-0814
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: Historically, tumor burden has been considered an impediment to efficacy of immunotherapeutic agents, including vaccines, stem cell transplant, cytokine therapy, and intravesical bacillus Calmette‐Guérin. This effect has been attributed to hypoxic zones in the tumor core contributing to poor T‐cell infiltration, formation of immunosuppressive stromal cells, and development of therapy‐resistant cell populations. However, the association between tumor burden and efficacy of immune checkpoint inhibitors is unknown. We sought to determine the association between radiographic tumor burden parameters and efficacy of immune checkpoint inhibitors in advanced lung cancer. Materials and Methods: We performed a retrospective analysis of patients with advanced lung cancer treated with immune checkpoint inhibitors. Demographic, disease, and treatment data were collected. Serial tumor dimensions were recorded according to RECIST version 1.1. Associations between radiographic tumor burden (baseline sum of longest diameters, longest single diameter) and clinical outcomes (radiographic response, progression‐free survival, and overall survival) were determined using log‐rank tests, Cox proportional‐hazard regression, and logistic regression. Results: Among 105 patients, the median baseline sum of longest diameters (BSLD) was 6.4 cm; median longest single diameter was 3.6 cm. BSLD was not associated with best radiographic, progression‐free survival, or overall survival. In univariate and multivariate analyses, no significant associations were observed for the other radiographic parameters and outcomes when considered as categorical or continuous variables. Conclusion: Although tumor burden has been considered a mediator of efficacy of earlier immunotherapies, in advanced lung cancer it does not appear to affect outcomes from immune checkpoint inhibitors. Implications for Practice: Historically, tumor burden has been considered an impediment to the efficacy of various immunotherapies, including vaccines, cytokines, allogeneic stem cell transplant, and intravesical bacillus Calmette‐Guérin. However, in the present study, no association was found between tumor burden and efficacy (response rate, progression‐free survival, overall survival) of immune checkpoint inhibitors in advanced lung cancer. These findings suggest that immune checkpoint inhibitors may provide benefit across a range of disease burden, including bulky tumors considered resistant to other categories of immunotherapy. Abstract : In the era of immune checkpoint inhibitor therapy, little is known about the effect of tumor burden on clinical outcomes. This article examines the association between multiple radiographic parameters of tumor burden and efficacy of immune checkpoint inhibitor therapy in lung cancer.