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ESMO 2020: Link Between TMB and Pembrolizumab Response in Urothelial Cancer?

By: Lauren Harrison, MS
Posted: Friday, October 30, 2020

Among patients with advanced urothelial cancer, tumor mutational burden (TMB) seems to be associated with improved outcomes with pembrolizumab monotherapy, but not chemotherapy. These data, which were generated from the KEYNOTE-052 and KEYNOTE-045 trials, were presented by Joaquim Bellmunt, MD, of Beth Israel Deaconess Medical Center, Boston, at the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (Abstract 747P).

The phase II KEYNOTE-052 trial used pembrolizumab monotherapy as first-line treatment in 374 patients with urothelial cancer that could not be treated with cisplatin. The phase III KEYNOTE-045 trial compared pembrolizumab with chemotherapy (including paclitaxel, docetaxel, and vinflunine) in 542 patients with platinum-refractory urothelial cancer. Researchers then correlated the TMB among patients in each trial with objective response rate, progression-free survival, and overall survival. TMB was assessed via whole-exome sequencing of tumor samples and matched DNA, and a high TMB was defined as more than 175 mutations/exome.

A total of 231 patients (62%) in the KEYNOTE-052 trial had available TMB data, and 39% of them had more than 175 mutations/exome. This higher TMB was found to be associated with a significantly higher objective response rate (P < .001) as well as longer progression-free (P = .001) and overall survival (P = .026) with pembrolizumab treatment.

An additional 370 patients (68%) in the KEYNOTE-045 trial had TMB data available, and 31% of them had a TMB of more than 175 mutations/exome. This higher degree of mutation was again associated with a higher objective response rate (P = .008) as well as longer progression-free (P = .002) and overall survival (P = .014) with pembrolizumab. Patients with a high TMB who received pembrolizumab had an objective response rate of 34.5%, compared with 15.8% of those with a lower TMB. Patients treated with chemotherapy had an objective response rate of 13.1% if they had a high TMB and 14.0% if they had a low TMB.

Disclosure: For a full list of author disclosures, visit oncologypro.esmo.org



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