Expression of PD-L1 as a Predictive Biomarker for Therapy Selection in mRCC
A newly published systematic review and meta-analysis of studies involving patients with metastatic renal cell carcinoma (mRCC) evaluates the predictive significance of PD-L1 expression in the treatment with immune checkpoint inhibitors.
Evaluated Parameters
The authors searched for works published up to April 2020 that evaluated objective response rates (ORR), complete response rates (CRR), disease progression (PDR), or progression-free survival (PFS) according to PD-L1 expression status in patients with mRCC. Six studies were included in the final analysis.
Findings
Positivity vs. Negativity of PD-L1
The results showed that compared to patients without PD-L1 positivity, treatment with immune checkpoint inhibitors in patients with PD-L1 expression was associated with significantly higher ORR (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.48−2.28) and CRR (OR 3.11; 95% CI 2.04−4.75) and significantly lower PDR (OR 0.43; 95% CI 0.31−0.60).
Checkpoint Inhibitors vs. Sunitinib
Therapy with immune checkpoint inhibitors was also associated with significantly longer PFS in patients with PD-L1 expression compared to treatment with sunitinib (hazard ratio [HR] 0.65; 95% CI 0.57−0.74), but this benefit of checkpoint inhibitors over sunitinib was not demonstrated in patients without PD-L1 expression.
In patients with PD-L1 expression, treatment with immune checkpoint inhibitors led to significantly higher ORR and longer PFS compared to sunitinib, regardless of the chosen immunotherapeutic. However, the highest probability of achieving the highest ORR and longest PFS was found with the combination of nivolumab + ipilimumab.
Conclusion
Immune checkpoint inhibitors are the cornerstone for the treatment of mRCC. However, they do not benefit all patients. Therefore, clinical decision-making based on the assessment of biomarkers is desirable. PD-L1 positivity in tumors should better identify mRCC patients who are likely to benefit from the use of checkpoint inhibitors, thus aiding in the personalization of treatment.
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Source:
Mori K., Abufaraj M., Mostafaei H. et al. The predictive value of programmed death ligand 1 in patients with metastatic renal cell carcinoma treated with immune-checkpoint inhibitors: a systematic review and meta-analysis. Eur Urol 2021 Jun; 79 (6): 783−792, doi: 10.1016/j.eururo.2020.10.006.
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