Chicago, Illinois—Pembrolizumab demonstrated anti-tumor activity in heavily pretreated patients with metastatic breast cancer and a high tumor mutational burden (TMB) in a recent phase 2 study being presented at the 2019 ASCO Annual Meeting.

“[Pembrolizumab] is an immune checkpoint inhibitor and H[high]TMB is an emerging predictive biomarker for checkpoint inhibitor therapy,” explained Ajjai Shivaram Alva, MBBS, University of Michigan, Ann Arbor, and colleagues.

The phase 2 TAPUR trial aimed to evaluate the anti-tumor activity of commercially available targeted agents in patients with advanced cancers with specific genomic alterations. Disease control (ie, objective response or stable disease at 16 weeks) was achieved in ≥2 of 10 patients in phase 1 of the study, leading to an additional 18 patients being enrolled.

These 28 patients with metastatic breast cancer, no standard treatment options, an Eastern Cooperative Oncology Group performance score 0 or 1, measurable disease, and acceptable organ function were enrolled in the trial between October 2016 and July 2018.

Commercially available tests were used for genomic testing, and patients matched to pembrolizumab had high TMB defined as ≥9 mutations/megabase (Muts/Mb) by a FoundationOne test (n = 20) or approved by the TAPUR Molecular Tumor Board for other tests (n = 8).

According to Dr Alva et al, if ≥7 patients have disease control, then the drug is considered worthy of further study. Other end points of the study include progression-free survival (PFS), overall survival (OS), and safety. 

Patients received pembrolizumab 2 mg/kg (n = 8) or 200 mg (n = 20) intravenously over 30 minutes every 3 weeks. High TMB ranged from 9 to 37 Muts/Mb.

Notably, Dr Alva and colleagues observed no relationship between Muts/Mb and PFS or OS.

Grade 3 adverse events included weight loss and hypoalbuminemia, and urinary tract infection was a grade 2 adverse event deemed possibly related to pembrolizumab.

Pembrolizumab demonstrated anti-tumor activity in heavily pre-treated patients with metastatic breast cancer and high TMB, warranting further study of pembrolizumab in this setting, Dr Alva and colleagues concluded.—Janelle Bradley

Alva AS, Mangat PK, Garret-Mayer E, et al. Pembrolizumab (P) in patients (pts) with metastatic breast cancer (MBC) with high tumor mutational burden (HTMB): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. Presented at: the 2019 ASCO Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 1014.