ROS1-Translokationen im nicht-kleinzelligen Lungenkarzinom

Zusammenfassung

Ziel: Zusammenfassung von Prävalenz, Testung und möglichen Behandlungsansätzen bei Patienten mit nicht-kleinzelligem Lungenkarzinom (NSCLC) und Aktivierung von ROS1.

Methodik: Internet-Recherche bezüglich klinischer und präklinischer Studien sowie Suche nach aktuellen Studien in amerikanischen Datenbanken.

Ergebnisse: Translokationen von ROS1 können zu einer Überexpression des Rezeptors führen und werden bei ungefähr 1 – 2 % aller NSCLC mit ganz überwiegender Prävalenz bei Adenokarzinomen gefunden. Standard des Nachweises sind derzeit Hybridisierungstechniken. Erste Ergebnisse aus Phase-I-Studien mit ROS1-Inhibitoren zeigen ein Ansprechen um 70 – 80 % und eine mediane progressionsfreie Überlebenszeit über 19 Monate bei insgesamt guter Verträglichkeit.

Schlussfolgerung: ROS1-Translokationen können gezielt und mit guten Ansprech- und Verlaufsdaten behandelt werden und sollten daher bei pulmonalen Adenokarzinomen im Stadium IV routinemäßig analysiert werden.

Abstract

Aim: Summary of prevalence, testing and treatment approaches in patients with non-small cell lung cancer (NSCLC) and ROS1 activation.

Methods: Internet-based search for clinical and preclinical studies as well as search for ongoing studies in web-based databases.

Results: ROS1 translocations lead to tyrosine kinase activation and can be detected in 1 – 2 % of all NSCLC and in 3 – 6 % of pulmonary adenocarcinoma patients, respectively, using in situ hybridization techniques. Results from phase I clinical studies using the ROS1 inhibitor crizotinib indicate response rates of 70 – 80 % and a median progression-free survival of about 19 months. The therapy was generally well tolerated.

Conclusions: NSCLC harbouring ROS1-translocations can be treated with targeted therapy leading to promising response and survival in patients. Hence, these alterations should be included into current molecular testing panels in stage IV pulmonary adenocarcinomas.

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