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RAD51B me as predictive biomarker for PD-1 blockade response in non-small cell lung cancer.

2020; Lippincott Williams & Wilkins; Volume: 38; Issue: 15_suppl Linguagem: Inglês

10.1200/jco.2020.38.15_suppl.e15235

1527-7755

I. Guerreiro, Daniela Barros‐Silva, Paula Lopes, Ana Luísa Cunha, João Lobo, Luís Antunes, Ana Rodrigues, Marta Soares, Rui Henrique, Cármen Jerónimo,

Epigenetics and DNA Methylation

e15235 Background: Lung cancer (LC) cells frequently express high levels of programmed death-ligand 1 (PD-L1). Although these levels grossly correlate with likelihood of response to specific checkpoint inhibitors, prediction of response is rather imperfect and, thus, more accurate predictive biomarkers are mandatory. We examined the methylation profile of RAD51B, a DNA-repair gene, as candidate predictive biomarker for efficacy of anti-PD-1 therapy in patients with non-small cell lung cancer (NSCLC), correlating with patients’ outcome. Methods: PD-L1 immunoexpression and RAD51B me levels were analysed in samples of NSCLC obtained from patients not treated with anti-PD-1 blockade (testing cohort) and patients treated with anti-PD-1 (validation cohort). Results: Of a total of 127 patients assessed, 58.3% depicted positivity for PD-L1 (PD-L1 + ). RAD51B me levels significantly associated with PD-L1 immunoexpression. Patients with clinical benefit from immunotherapy disclosed higher RAD51B me levels (p = 0.04) and significantly higher median progression free survival (PFS) (p = 0.02). PD-L1 + was also associated with longer overall survival (p = 0.03). Conclusions: We demonstrated that RAD51B me levels might be combined with validated predictive biomarker PD-L1 immunostaining to select patients who will most likely experience clinical benefit from PD-1 blockade. The predictive value of RAD51B me should be confirmed in prospective studies.