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In 62 women with metastatic triple-negative cancer treated with immunotherapy, high mutation burden (18%) went with a year of progression-free time versus under four months, while PTEN loss (29%) went with almost no responses.
62 patients with metastatic TNBC who consented to targeted DNA sequencing and were treated with anti-PD-1/L1 therapy on trials at Dana-Farber (2014 to 2019) alone (23%), with targeted therapy (19%) or chemotherapy (58%). High TMB (10 or more nonsynonymous mutations/Mb; 18%) was associated with longer progression-free survival (12.5 versus 3.7 months; P 0.04); PTEN alterations (nonsynonymous mutation or one- or two-copy deletion; 29%) with lower objective response (6% versus 48%), shorter PFS (2.3 versus 6.1 months) and shorter overall survival (9.7 versus 20.5 months), independent of performance status, prior lines, regimen, visceral disease and PD-L1, and not seen in chemotherapy-treated (90) or non-immunotherapy (169) cohorts.
PTEN loss, the most common PI3K-pathway lesion in TNBC, may mark primary immunotherapy resistance, and TMB may add to PD-L1 in choosing who gets checkpoint blockade.
Shares Nancy U. Lin, TMB-high (tumour mutational burden >= 10 mutations per megabase), Sara M. Tolaney, Tumour mutational burden (TMB).
Shares Dana-Farber Brigham Cancer Center, PD-L1, PD-1, Immune checkpoint inhibitors.
Shares Sara M. Tolaney, Clinical Cancer Research, Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC).
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC).
Shares PTEN alteration (sequencing) and PTEN loss (IHC), PTEN, Metastatic triple-negative breast cancer, Triple-negative breast cancer (TNBC).
Shares Nancy U. Lin, Dana-Farber Brigham Cancer Center, Triple-negative breast cancer (TNBC).
Shares Dana-Farber Brigham Cancer Center, PD-1, Immune checkpoint inhibitors.
Shares Metastatic triple-negative breast cancer, PD-1, Triple-negative breast cancer (TNBC).