SITC 2020: Tumor Mutation Burden and Response to Immunotherapy in Advanced Urothelial Cancer
Posted: Monday, November 30, 2020
In urothelial carcinoma, the measure of tumor mutation burden (TMB) in tumor or blood has been linked to increased efficacy with PD-1/PD-L1 inhibitors. Michiel van der Heijden, MD, PhD, of Netherlands Cancer Institute, and American colleagues, compared the use of standard-of-care chemotherapy versus the PD-L1 inhibitor durvalumab, either alone or paired with the CTLA-4 inhibitor tremelimumab, in unresectable, metastatic, or locally advanced urothelial carcinoma. This study was presented at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 266) and published in the Journal for ImmunoTherapy of Cancer.
“Both blood TMB and tumor TMB are potentially useful biomarkers for enriching responses to durvalumab plus tremelimumab in previously untreated, advanced urothelial carcinoma,” concluded the study authors.
Baseline plasma samples of 1,032 patients from the phase III DANUBE trial were examined for tumor TMB and blood TMB. Of these patients, 536 and 623 were evaluated for TMB in blood and TMB in tumor, respectively. Correlations between progression-free survival, median overall survival, and landmark overall survival with these biomarkers were analyzed.
TMB in blood and TMB in tumor were not associated with progression-free survival or any overall survival in durvalumab versus standard-of-care chemotherapy. As blood TMB cutoffs increased, there were stronger associations between blood TMB, overall survival, and progression-free survival with durvalumab plus tremelimumab. Overall survival rates at the 24 mut/Mb or greater blood TMB cutoff for standard-of-care chemotherapy and durvalumab plus tremelimumab were 54.3% and 76.7% at 12 months, respectively. However, at the less than 24 mut/Mb cutoff rates were 51.2% and 53.4% for standard-of-care chemotherapy and durvalumab plus tremelimumab, respectively. These trends were similarly observed for both progression-free survival and overall survival in the tumor TMB groups.
Disclosure: For full disclosures of the study authors, visit jitc.bmj.com.