ERCC1 as Predictor of Platinum Benefit in Non–Small-Cell Lung Cancer
Mené sur 648 patients atteints d'un cancer du poumon non à petites cellules de stade avancé, cet essai de phase III évalue, en fonction du type histologique de la tumeur (épidermoïde ou non) et du point de vue de la survie globale, la supériorité d'un traitement sans sels de platine par rapport à un traitement à base de cisplatine, puis évalue l'intérêt de déterminer le statut tumoral des protéines ERCC1 et XPF pour orienter le choix thérapeutique et améliorer la survie
In the era of precision medicine, it is somewhat striking that targeted therapies are frequently prescribed when predictive molecular alterations, such as EGFR or B-RAF mutation, ALK translocation, and HER2 amplification, are present in the patient’s tumor, whereas conventional cytotoxic chemotherapies (CCC) are still being used in a one-size-fits-all approach. Customizing the choice of chemotherapy to a specific tumor molecular profile—to maximize treatment efficacy and avoid deleterious toxicities—is a sound endeavor, but has proven difficult to achieve. Indeed, most efforts that have been spent on developing clinical-grade predictive biomarkers for CCC have not passed the prospective validation step, and there currently is no robust and validated companion biomarker routinely used in clinic. In non–small-cell lung cancer (NSCLC), where platinum salts are the cornerstone of treatment, excision repair cross complementation group 1 (ERCC1)—the rate-limiting enzyme of the nucleotide excision repair pathway—represents the most promising biomarker for customizing patient therapy. In the article that accompanies this editorial, Lee et al present results from the randomized phase III ERCC1 Trial, which prospectively evaluated ERCC1 testing as a predictive biomarker of platinum therapy efficacy in patients with advanced NSCLC. This trial, which was initially designed to include 1,272 patients, was stopped prematurely after a significantly poorer overall survival (OS) for nonplatinum therapy in the squamous NSCLC group (median OS, 8.7 months v 11.4 months). On the basis of a cohort of 648 patients, investigators did not find any predictive value for expression of ERCC1 or xeroderma pigmentosum F (XPF; the partner of ERCC1 that possesses the endonuclease activity) with regard to platinum sensitivity, nor did they find any prognostic value for these biomarkers for OS or progression-free survival (PFS).
Journal of Clinical Oncology , éditorial en libre accès, 2015