Dataset Information
Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer.
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ABSTRACT: Purpose
Few patients with metastatic triple-negative breast cancer (mTNBC) benefit from immune checkpoint inhibitors (ICI). On the basis of immunotherapy response correlates in other cancers, we evaluated whether high tumor mutational burden (TMB) ≥10 nonsynonymous mutations/megabase and PTEN alterations, defined as nonsynonymous mutations or 1 or 2 copy deletions, were associated with clinical benefit to anti-PD-1/L1 therapy in mTNBC.Experimental design
We identified patients with mTNBC, who consented to targeted DNA sequencing and were treated with ICIs on clinical trials between April 2014 and January 2019 at Dana-Farber Cancer Institute (Boston, MA). Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were correlated with tumor genomic features.Results
Sixty-two women received anti-PD-1/L1 inhibitors alone (23%) or combined with targeted therapy (19%) or chemotherapy (58%). High TMB (18%) was associated with significantly longer PFS (12.5 vs. 3.7 months; P = 0.04), while PTEN alterations (29%) were associated with significantly lower ORR (6% vs. 48%; P = 0.01), shorter PFS (2.3 vs. 6.1 months; P = 0.01), and shorter OS (9.7 vs. 20.5 months; P = 0.02). Multivariate analyses confirmed that these associations were independent of performance status, prior lines of therapy, therapy regimen, and visceral metastases. The survival associations were additionally independent of PD-L1 in patients with known PD-L1 and were not found in mTNBC cohorts treated with chemotherapy (n = 90) and non-ICI regimens (n = 169).Conclusions
Among patients with mTNBC treated with anti-PD-1/L1 therapies, high TMB and PTEN alterations were associated with longer and shorter survival, respectively. These observations warrant validation in larger datasets.
SUBMITTER: Barroso-Sousa R
PROVIDER: S-EPMC7269810 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
Tumor Mutational Burden and <i>PTEN</i> Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research 20200204 11
<h4>Purpose</h4>Few patients with metastatic triple-negative breast cancer (mTNBC) benefit from immune checkpoint inhibitors (ICI). On the basis of immunotherapy response correlates in other cancers, we evaluated whether high tumor mutational burden (TMB) ≥10 nonsynonymous mutations/megabase and <i>PTEN</i> alterations, defined as nonsynonymous mutations or 1 or 2 copy deletions, were associated with clinical benefit to anti-PD-1/L1 therapy in mTNBC.<h4>Experimental design</h4>We identified pati ...[more]