Abstract
IntroductionProgrammed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. Lower positivity rates but a larger relative benefit from atezolizumab has been implied when PD-L1 status is assessed at metastatic sites. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility. MethodsCochrane Library, Embase, Medline and Web of science were searched for studies reporting on PD-L1 expression in primary and metastatic breast cancer, followed by data extraction. Outcomes included pooled PD-L1 positivity rates in tumor cells, immune cells or both in primary tumor and metastasis, PD-L1 discordance between matched primary tumors and metastasis and direction of discordance. ResultsOf 2552 identified entries following de-duplication, 20 studies fulfilled the predefined inclusion criteria. Pooled PD-L1 positivity rate was higher in primary tumors compared to metastasis when assessed in immune cells (51.2% vs 37.1% p < 0.001) and tumor/immune cells (30.1% vs 14.6% p < 0.001), but not in tumor cells (18.7% vs 17.8% p = 0.65). PD-L1 positivity was lowest when assessed in bone metastases (12%) and highest in lymph nodes (60%). Discordance between primary tumors and metastasis was bidirectional, with higher pooled discordance rates when PD-L1 expression was assessed in immune compared to tumor cells (39.5% vs 13.6%, p < 0.001). ConclusionThe observed considerable discordance between PD-L1 status in primary and metastatic breast cancer emphasizes the importance of appropriate tissue sampling when selecting patients for immunotherapy.
Highlights
Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer
Patients who were PD-L1 positive at a metastatic site seemed to have a greater relative benefit from atezo lizumab (HR = 0.55, 95% CI 0.32–0.93) than patients who were PD-L1 positive at the primary tumor (HR = 0.79, 95% CI 0.57–1.09) [13,14]
Data regarding tissue origin in the positive KEYNOTE355 trial of first-line pembrolizumab for metastatic TNBC, where PD-L1 was assessed according to 22C3 clone and Combined Positive Score (CPS), are not yet published [12]
Summary
Programmed cell death ligand 1 (PD-L1) expression is predictive for benefit from immunotherapy in several human malignancies including triple negative breast cancer. We aimed to study the discordance of PD-L1 expression between primary tumor and metastasis in breast cancer due to its potential clinical utility. Combined chemoimmunotherapy has been shown in randomized trials to be effective both at the neoadjuvant and the metastatic settings [9,10,11,12] In the latter, updated results from the IMPassion130 study demonstrate that the addition of atezolizumab to first line nab-paclitaxel does not improve overall survival (OS) in the intention-to-treat population (Hazard Ratio [HR] = 0.86, 95% Confi dence Interval [CI] 0.72–1.02; p = 0.078). Only 37.4% of patients had undergone a metastatic biopsy These were less often PD-L1 positive than patients for whom only primary BC tissue was assessed (36% vs 44%; p = 0.014). Data regarding tissue origin in the positive KEYNOTE355 trial of first-line pembrolizumab for metastatic TNBC, where PD-L1 was assessed according to 22C3 clone and Combined Positive Score (CPS), are not yet published [12]
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