Dissociated response and clinical benefit in patients treated with nivolumab monotherapy

Abstract

Immune checkpoint inhibitors (ICIs) are effective for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, an unconventional response pattern is sometimes encountered. A dissociated response (DR), characterized by some lesions shrinking and others growing, has been recognized with ICI treatment. In this study, we examined the characteristics and treatment outcomes of DR in previously treated NSCLC patients, receiving nivolumab monotherapy. We conducted a retrospective cohort study of previously treated patients with advanced NSCLC who received nivolumab. We assessed the tumor response of each organ using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at the first radiologic evaluation. We investigated treatment outcome and compared overall survival using the Kaplan-Meier Method and log-rank tests. Further, we conducted the same analysis in patients who had previously received chemotherapy or tyrosine kinase inhibitor therapy in our hospital. Between April 2016 and September 2018, 107 patients who received nivolumab fulfilled the inclusion criteria. Of them, 5 (5%) patients showed a DR. There were no specific differences in characteristics between DR and non-DR cases. Patients showing DR had significantly longer overall survival than those showing concordant progressive disease (46.9 vs. 8.2 months, p = 0.038). The frequencies of DR in the ICI, chemotherapy, and tyrosine kinase inhibitor-treated cohorts were 5%, 1%, and 4%, respectively. DR was uncommon, but this presented a distinctive pattern of nivolumab response. Some patients might benefit from continuing nivolumab therapy and may achieve a longer overall survival.

Keywords: Dissociated response; Immune checkpoint inhibitor; Immunotherapy; Mixed response; Nivolumab; Non-small cell lung cancer.