PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer
Menée à partir de l'analyse immunohistochimique d'échantillons tumoraux prélevés sur 982 patients atteints d'un cancer du poumon non à petites cellules traité par résection, cette étude met en évidence l'absence d'association entre l'expression de la protéine PD-L1 et le bénéfice, en termes de survie, d'une chimiothérapie adjuvante
Background : The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC.
Patients and methods : Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using a previously validated E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TC) and immune cells (IC) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy.
Results : Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%) and 204 (20.8%) tumor samples were positive for PD-L1 staining on tumor cells using cut-offs at ≥ 1% and ≥25%, respectively. For PD-L1 expressing immune cells, 380 (38.7%) and 148 (15.1%) were positive at ≥ 1% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy.
Conclusions : PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.
Annals of Oncology , résumé, 2016