Virtual Library
Start Your Search
Johnathan Man
Author of
-
+
P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.07-018 - A Meta-Analysis of PD-L1 Expression as a Biomarker of PD-1 Blockade in Advanced Non Small Cell Lung Cancer (ID 9225)
09:30 - 09:30 | Presenting Author(s): Johnathan Man
- Abstract
Background:
The recognition of programmed cell death 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) as key therapeutic targets has led to the clinical development of several PD-1 and PD-L1 inhibitors as breakthrough treatments in advanced non small cell lung cancer. Although some patients experience durable tumour response, many do not derive any clinical benefit, therefore highlighting the importance of identifying methods to improve patient selection. 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.
Method:
We 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 4,452 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= 3,631) 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.
Conclusion:
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.
