Efficacy of crizotinib in ROS1-rearranged lung cancer: The European experience.

Tumor Biology
Session Type and Session Title: 
Poster Highlights Session, Tumor Biology
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 11035)
Julien Mazieres, Gerard Zalcman, Lucio Crino, Pamela Biondani, Benjamin Besse, Anne-Marie C. Dingemans, Hervé Lena, Isabelle Monnet, Sacha Rothschild, Federico Cappuzzo, Luc Thiberville, Damien Rouvière, Rafal Dziadziuszko, Egbert F. Smit, Juergen Wolf, Christian Spirig, Nicolas Pécuchet, Joachim Diebold, Julie Milia, Oliver Gautschi; Hôpital Larrey CHU Toulouse, Toulouse, France; Caen University Hospital, Caen, France; University of Perugia, Perugia, Italy; Gustave Roussy, Cancer Campus, Grand Paris, Villejuif, France; Gustave Roussy, Villejuif, France; University Hospital Maastricht, Maastricht, Netherlands; CHU de Rennes, Hôpital Pontchailloux, Rennes, France; CHI of Creteil, Creteil, France; University Hospital Basel, Basel, Switzerland; Istituto Toscano Tumori-Ospedale-Civile-Livorno, Livorno, Italy; CHU Pneumologie, Rouen, France; CHU Toulouse, Hôpital Larrey, Toulouse, France; Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland; VU University Medical Center, Amsterdam, Netherlands; University Hospital Cologne, Cologne, Germany; Hirslanden Klinik St. Anna, Luzern, Switzerland; Hôpital Européen Georges Pompidou (HEGP), Assistance Publique Hôpitaux de Paris (APHP), Paris, France; Pathologisches Institut, Luzern, Switzerland; Hôpital Larrey, CHU Toulouse, Toulouse, France; Department of Medical Oncology, Luzerner Kantonsspital, Luzern, Switzerland

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Abstract Disclosures


Background: ROS1 chromosomal rearrangement (ROS1+) was described as an oncogenic driver in approximately 1% of non-small cell lung cancers (NSCLC). Due to the structural analogy of ROS1 and ALK, crizotinib is a potent inhibitor of both targets. An expansion cohort of a phase I trial reported promising activity [Ou et al., ASCO 2013]. Here, we describe the characteristics and outcomes of ROS1+ NSCLC patients treated with crizotinib in a large European case series. Methods: We conducted a retrospective study among European clinicians screening ROS1+ NSCLC. Eligible patients had advanced NSCLC, known ROS1+ NSCLC diagnosed by FISH and received crizotinib for at least 1 week at the dose of 250 mg BID through national access program or an individual off-label use basis. Treatment response was performed according to RECIST criteria version 1.1. Informed consent and IRB approval were obtained according to local regulations. Data were analyzed centrally. Results: We identified 28 ROS1+ NSCLC patients treated with crizotinib. Our population was characterized by a median age of 58 yr (34 to 78 yr), a gender-ratio of 17 women and 11 men and a high proportion of never smokers (n = 19, 67.9%). All the patients had stage IV disease and were pretreated with none (n=2), one (n = 8), two (n = 5), three (n = 3) or more (n = 10) lines of chemotherapy before the administration of crizotinib. All tumors were adenocarcinomas including 4 with lepidic pattern. ROS1 rearrangement was the exclusive driver except for 2 tumors with concomitant KRAS mutation. Twenty-six patients were evaluable for response (the waterfall plot will be presented at the meeting). We observed 3 progressive diseases, 3 stable diseases and 20 objective responses including 4 complete responses (overall response rate 77%, disease control rate 88%). Crizotinib primary resistance was associated with concomitant KRAS mutation or progression in the brain. Crizotinib was generally well tolerated and no unexpected adverse effects were observed. Conclusions: These results confirm the high crizotinib activity in ROS1+ NSCLC. Further patients should be treated in ongoing clinical trials to test the long-term activity of ROS1 inhibitors.