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PD-L1 mRNA Baseline Expression May Indicate Response to Atezolizumab Plus Nab-paclitaxel in TNBC

The patterns of PD-L1 mRNA expression in plasma-derived exosomes at baseline corresponded to response to atezolizumab plus nab-paclitaxel and survival in patients with triple negative breast cancer
01 Mar 2021
Breast cancer;  Cancer Immunology and Immunotherapy

Patients with unresectable locally advanced triple negative breast cancer (TNBC) and higher levels of PD-L1 mRNA expression in plasma-derived exosomes at baseline demonstrated greater response to atezolizumab plus nab-paclitaxel, according to findings presented at the ESMO Targeted Anticancer Therapies (TAT) Virtual Congress 2021 held on 1-2 March. Furthermore, the levels of mRNA decreased with successful treatment while the copy number increased in patients experiencing disease progression following atezolizumab plus nab-paclitaxel.

Citing the paucity of reliable indicators of response in TNBC, Lucrezia Raimondi of the UOC Territorial Oncology of Aprilia, Sapienza University of Rome in Aprilia, Italy and co-investigators conducted this study to evaluate whether PD-L1 mRNA copies per ml in plasma-derived exosomes may predict the response to anti-PD-L1 antibodies early in the course of therapy.

This analysis included data from 77 consecutive patients with unresectable locally advanced TNBC who were treated with atezolizumab plus nab-paclitaxel. Blood draws were obtained from the patients at baseline, and at 28 and 56 days after initiation of treatment. The levels of exosomal PD-L1 mRNA in plasma was determined using the Bio-Rad QX100 digital droplet PCR system and exoRNeasy kit and the objective response was defined according to RECIST v1.1 criteria.

PD-L+ mRNA copies at baseline corresponded to response

The 28 patients achieving complete response (CR) and partial response (PR) had a significantly higher number of PD-L1 mRNA copies per ml compared to 49 patients showing stable disease (SD) or progressive disease (PD); the mean value (standard error of mean [s.e.m.] was 785.6 (±121.1) copies/ml compared to 114.7 (±31.4), respectively (p < 0.001).

The mRNA copy level decreased with treatment. Patients showing CR and PR demonstrated mean PD-L1 copies/ml of 747.6±121.1 at baseline that was reduced to 175.4 copies/ml at 2 months post treatment (p = 0.001). Patients with SD had mRNA levels that remained relatively constant from baseline to 2 months post treatment; mean (± s.e.m.) values were 270 (±71.1) and 217.5 (±17.3) copies per ml, respectively (p = 0.614). Levels of PD-L1 mRNA copies increased with treatment in patients showing PD from 124.1 (±31.2) at baseline to 494.3 (±46.2) copies per ml at 2 months post treatment (p < 0.001).

PD-L1-mRNA-Baseline-Expression-May-Indicate-Response-to-Atezolizumab-Plus-Nab-paclitaxel-in-TNBC

Changes of PD-L1 expression in plasma-derived exosomes may provide useful information on response to treatment with atezolizumab plus nab-paclitaxel in triple negative breast cancer. At baseline, patients with complete and partial response showed a significantly higher number of PD-L1 mRNA copies per mL compared to ones with stable or progressive disease. Two months after the start of treatment, PD-L1 levels in plasma-derived exosomes significantly decreased in patients responding to treatment and increased in subjects with disease progression. CR complete response; PR partial response; SD stable disease; PD progressive disease.

© Lucrezia Raimondi.

Increased PD-L1 mRNA with treatment was associated with shorter survival

Patients having an increase of PD-L1 mRNA copies per ml following treatment with atezolizumab plus nab-paclitaxel demonstrated significantly shorter progression-free survival (p = 0.007). Overall survival (OS) was 5 months in these patients (range, 2 to 7 months, 95% confidence interval 1.1-6.1) as compared to OS that was more than doubled (range, 8-15 months) in patients not showing an increase in mRNA with treatment (p = 0.001).

Conclusion

The investigators concluded that these data suggest that exosomal PD-L1 mRNA levels are significantly associated with outcome and response to atezolizumab plus nab-paclitaxel.

This study did not receive external funding. 

Reference

23P – Raimondi L, Raimondi FM, Lazzeroni R, et al. Prediction of response to atezolizumab plus nab-paclitaxel in unresectable locally advanced triple negative breast cancer (TNBC): The clinical usefulness of PD-L1 mRNA expression in plasma-derived exosomes. ESMO Targeted Anticancer Therapies (TAT) Virtual Congress (1-2 March 2021).

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