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PD-L1 Expression as a Biomarker of PD-1 Blockade in Advanced NSCLC

PD-L1 expression on tumour cells with or without immune cells is the most reported association with anti-tumour activity of PD-1 blockade. Despite multiple publications, the use of different assays and cutpoints make it difficult to know if PD-L1 is a reliable biomarker for predicting outcomes to anti PD-1/PD-L1 treatment.
Within the limitations of current data, there is a positive correlation between increasing cutpoints of PD-L1 expression and ORR and 1yr PFS, but little correlation with 1yr OS in treatment naive and pretreated patients (Gebski V et al., P1.07-018).

Method

Man J et al. performed a systematic search of MEDLINE, EMBASE, PubMed and conference proceedings up to 20 June 2017 and identified all clinical trials of anti PD-1 or PD-L1 monotherapy in advanced non-small cell lung cancer. We retrieved data regarding outcomes of 1 year overall survival (1yr OS), 1 year progression free survival (1yr PFS) and overall response rate (ORR), including 95 % confidence intervals, in subgroups of varying PD-L1 tumour expression with cutpoints of 1 %, 5 %, 10 %, 25 %, 50 % and 90 %. Results were pooled and analysed based on different cutpoints. As PD-L1 expression is a continuum, we also tested for a correlation between outcomes and increasing cut-points of PD-L1 expression.

Result

Of sixteen included studies with a total of 4452 patients who received PD-1/PD-L1 inhibitor monotherapy, eight trials (n = 821) reported on PD-1 blockade as first-line (1L) therapy and thirteen trials (n= 3631) reported on treatment as second-line or beyond (> 2L). Using 1 % cutpoint, PD-L1 positivity was associated with higher ORR in 1L and > 2L and 1yr PFS in > 2L. Using a high cutpoint of 50 %, PD-L1 positivity was associated with higher ORR in 1L and > 2L, and higher PFS in 1L. Comparison of increasing cutpoints of PD-L1 expression and outcomes showed a positive correlation with 1yr PFS in 1L, a modest correlation with 1yr PFS in > 2L and ORR in 1L and > 2L, and little correlation with 1yr OS in 1L and > 2L. Sensitivity analysis revealed no difference when excluding studies using the SP142 assay with weaker tumour staining.

References:
Man J et al., abstract P1.07-018: A Meta-Analysis of PD-L1 Expression as a Biomarker of PD-1 Blockade in Advanced Non Small Cell Lung Cancer

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