Atezolizumab plus nanoparticle albumin-bound (nab)-paclitaxel prolonged progression-free survival (PFS) and overall survival (OS) among patients with unresectable locally advanced TNBC but its use is hampered by the lack of reliable predictors of tumor response. The study evaluates whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict response to anti-PD-L1 antibodies early in the course of therapy.
Seventy-seven consecutive patients with unresectable locally advanced TNBC treated with atezolizumab plus nab-paclitaxel were studied by blood draws at baseline, 28 days and 56 days after initiation of treatment. Exosomal PD-L1 mRNA in plasma was determined using Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit. Objective responses were defined following the RECIST criteria v.1.1.
At baseline, patients with complete and partial response (CR+PR, n=28) displayed a significantly higher number of PD-L1 mRNA copies per ml compared to ones with stable or progressive disease (SD+PD, n=49) (mean value: 785.6±121.1 vs 114.7±31.4, p<0.001). In patients with CR and PR mean PD-L1 copies/ml were 747.6±121.1 and 125.4 at baseline vs 2 months, respectively (p=0.001). In patients with stable disease the mean ± s.e.m. values were 270±71.1 vs 217.5±17.3 copies per ml (p=0.614) while in progressive disease PD-L1 mRNA levels were 122.1±31.2 vs 494.3±46.2 copies per ml at baseline vs 2 months, respectively (p<0.001). Patients with an increase of PD-L1 mRNA copies per ml were also characterized by significantly shorter PFS (p=0.007) and shorter OS (p=0.001) (OS: 5 months (range 2-7 months, 95%CI 1.1-6.1) vs more than double (range 8-15 months).
Despite the study’s limitations, our data suggest exosomal PD-L1 is significantly associated with outcome and response to atezolizumab plus nab-paclitaxel.
The authors.
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All authors have declared no conflicts of interest.