Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer—final results of the EUCROSS trial

In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the...

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Published in:	ESMO open Vol. 9; no. 2; p. 102237
Main Authors:	Michels, S., Massutí, B., Vasyliv, I., Stratmann, J., Frank, J., Adams, A., Felip, E., Grohé, C., Rodriguez-Abreu, D., Bischoff, H., Carcereny i Costa, E., Corral, J., Pereira, E., Fassunke, J., Fischer, R.N., Insa, A., Koleczko, S., Nogova, L., Reck, M., Reutter, T., Riedel, R., Schaufler, D., Scheffler, M., Weisthoff, M., Provencio, M., Merkelbach-Bruse, S., Hellmich, M., Sebastian, M., Büttner, R., Persigehl, T., Rosell, R., Wolf, J.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-02-2024 Elsevier
Subjects:	crizotinib EUCROSS lung cancer Original Research overall survival ROS1 lung cancer EUCROSS overall survival crizotinib ROS1
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Summary:	In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low. •Median overall survival with crizotinib in ROS1-positive lung cancer was 54.8 months.•Co-occurring TP53 aberrations constitute a subgroup with impaired prognosis.•Central nervous system disease control is durable.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Prior affiliation during the trial: Hospital Universitario Virgen del Rocío, Sevilla, Spain.
ISSN:	2059-7029 2059-7029
DOI:	10.1016/j.esmoop.2024.102237