Single-arm, open label prospective trial to assess prediction of the role of ERCC1/XPF complex in the response of advanced NSCLC patients to platinum-based chemotherapy

• Published in: ESMO open 2021-02, Vol.6 (1), p.100034-100034, Article 100034
• Main Authors: Ganzinelli, M., Linardou, H., Alvisi, M.F., Caiola, E., Lo Russo, G., Cecere, F.L., Bettini, A.C., Psyrri, A., Milella, M., Rulli, E., Fabbri, A., De Maglie, M., Romanelli, P., Murray, S., Broggini, M., Marabese, M., Garassino, M.C.
• Format: Article
• Language: English
• Subjects: ERCC1; NSCLC; Original Research; platinum-based chemotherapy; proximity ligation assay; XPF
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2020.100034

Platinum-based therapy, combined or not with immune checkpoint inhibitors, represents a front-line choice for patients with non-small-cell lung cancer (NSCLC). Despite the improved outcomes in the last years for this malignancy, only a sub-group of patients have long-term benefit. Excision repair cross-complementation group 1 (ERCC1) has been considered a potential biomarker to predict the outcome of platinum-based chemotherapy in NSCLC. However, the ERCC1 gene is transcribed in four splice variants where the isoform 202 was described as the only one active and able to complex Xeroderma pigmentosum group F-complementing protein (XPF). Here, we prospectively investigated if the active form of ERCC1, as assessed by the ERCC1/XPF complex (ERCC1/XPF), could predict the sensitivity to platinum compounds. Prospectively enrolled, patients with advanced NSCLC treated with a first-line regimen containing platinum were centrally evaluated for ERCC1/XPF by a proximity ligation assay. Overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) were analyzed. The absence of the ERCC1/XPF in the tumor suggested a trend of worst outcomes in terms of both OS [hazard ratio (HR) 1.41, 95% confidence interval (CI) 0.67-2.94, P = 0.373] and PFS (HR 1.61, 95% CI 0.88-3.03, P = 0.123). ORR was marginally influenced in ERCC1/XPF-negative and -positive groups [odds ratio (stable disease + progressive disease versus complete response + partial response) 0.87, 95% CI 0.25-3.07, P = 0.832]. The lack of ERCC1/XPF complex in NSCLC tumor cells might delineate a group of patients with poor outcomes when treated with platinum compounds. ERCC1/XPF absence might well identify patients for whom a different therapeutic approach could be necessary. •This is the first study investigating the ERCC1/XPF complex as a platinum-based therapy response biomarker in NSCLC.•The lack of ERCC1/XPF complex might delineate a group of patients with poor outcomes when treated with platinum compounds.•ERCC1/XPF absence might identify tumors for whom a different therapeutic approach than platinum compounds could be necessary.