Abstract 5840
Background
ROS1 fusions are found in 1% of lung cancer patients. EUCROSS is the first prospective European trial to evaluate crizotinib in this patient subset. Here we present an updated analysis of the progression-free survival (PFS), overall survival (OS) and molecular characteristics of progression.
Methods
Multi-centre, single arm phase II trial. Key eligibility criteria: ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearrangement. Treatment: 250 mg crizotinib BID. Key endpoints of this report: updated PFS (according to RECIST 1.1) and OS and molecular tumour characterization.
Results
Thirty patients were eligible for response evaluation (N = 30; intention-to-treat population, N = 34). Median follow-up was 44.9 months (95% CI, 39.6-47.4). At data-cut off 19 patients (63.3%) discontinued treatment due to progression or death. Investigator-assessed efficacy: ORR, 70% (95% CI, 51–85; 21/30); disease control rate, 90.0% (95% CI, 73.5-97.9; 27/30); median PFS, 19.4 months (95% CI, 10.1-31.2); 24-months-OS probability, 65.5% (95% CI, 48.3-82.9). Prevalence of co-occurring genetic aberrations by hybrid-capture sequencing was 61%. TP53 mutations were most frequent (28%; 5/18). PFS (p = 0.0219) and OS at 24 months (p = 0.015) were significantly shorter in TP53-mutant patients. Tissue or blood samples were collected in six patients at progression. In three (50%) samples, secondary mutations in ROS1 (i.e. p.G2032R (N = 2), p.L2026M (N = 1)) were detected. In one (17%), a PIK3CA mutation (p.E545K) was identified. In the other two patients (33%) aberrations of unknown significance were detected.
Conclusions
Updated PFS and OS results confirm the efficacy of crizotinib in ROS1-rearranged lung cancer patients. Patients with co-mutations in TP53 had significantly worse outcomes compared to TP53 wild-type patients. The most common mechanisms of resistance were mutations in ROS1. Next-generation ROS1 inhibitors or the multi-kinase inhibitor cabozantinib may be promising treatment options for these patients.
Clinical trial identification
NCT02183870.
Editorial acknowledgement
Legal entity responsible for the study
University Hospital of Cologne.
Funding
Pfizer.
Disclosure
S. Michels: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Boehringer Ingelheim; Research grant / Funding (institution): Janssen; Honoraria (self): Roche. B. Massuti Sureda: Honoraria (self): Merck Sharp Dome; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): Pfizer. H. Schildhaus: Honoraria (self): ZytoVision; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Novartis. M. Sebastian: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp Dome; Honoraria (self): Takeda; Honoraria (self): Mediolanum; Honoraria (self): AbbVie; Honoraria (self): Celgene. E. Felip: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Guardiant; Honoraria (self): Merck Sharp Dome; Honoraria (self): Merck KGa; Honoraria (self): Novartis. M. Reck: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca; Honoraria (self): Abbot; Honoraria (self): Celgene; Honoraria (self): Merck Sharp Dome; Honoraria (self): Merck KGa; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche. S. Merkelbach-Bruse: Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Roche; Honoraria (self), Research grant / Funding (institution): Novartis. L. Nogova: Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Janssen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): Celgene. J. Wolf: Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Janssen; Honoraria (self): Boehringer Ingelheim; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Chugay; Honoraria (self): Ignyta; Honoraria (self): Eli Lilly; Honoraria (self): Merck Sharp Dome; Honoraria (self): Roche. All other authors have declared no conflicts of interest.
Resources from the same session
4925 - Prognostic role of CD73 in metastatic Non Small Cell Lung Cancer according to the presence of driver alterations
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract
785 - JAK-STAT inhibitor overcomes interferon γ-reduced, NK cell-mediated cytotoxicity in non-small-cell lung cancer cells
Presenter: Riki Okita
Session: Poster Display session 1
Resources:
Abstract
2326 - Low LATS2 expression is associated with poor prognosis in non small cell lung cancer
Presenter: Si-hyong Jang
Session: Poster Display session 1
Resources:
Abstract
5960 - Application of ESCAT and OncoKB scales in Liquid biopsy (LB) in Advanced NSCLC patients (pts): Is it feasible and reliable?
Presenter: Michael McCusker
Session: Poster Display session 1
Resources:
Abstract
4855 - IDH1R132H mutation induces a less aggressive phenotype of glioma cells and affects the radiosensitivity by interacting with Wnt/β-catenin signaling
Presenter: Xuetao Han
Session: Poster Display session 1
Resources:
Abstract
2641 - Impact of Angiopoietin-2 on glioblastoma response to combined chemo-radiotherapy
Presenter: Charly Helaine
Session: Poster Display session 1
Resources:
Abstract
5743 - The Discovery of RNA-aptamers That Selectively Bind and Inhibit Glioblastoma Stem Cells by targeting EphA2
Presenter: Alessandra Affinito
Session: Poster Display session 1
Resources:
Abstract
4160 - Impact of tumor reoxygenation by nanoparticles on Tumor Associated Macrophages (TAMs)
Presenter: Aurélie Ferré
Session: Poster Display session 1
Resources:
Abstract
2474 - Prognostic significance of c-Rel/p50 heterodimer in the tumor microenvironment of uveal melanoma
Presenter: Seema Kashyap
Session: Poster Display session 1
Resources:
Abstract
1769 - Synergistic role of BAP1 and DNA damage response pathway in uveal melanoma and its prognostic significance.
Presenter: JAYANTI JHA
Session: Poster Display session 1
Resources:
Abstract