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Efficacy of crizotinib in ROS1-rearranged lung cancer: The European experience.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
Abstracts by Julien Mazieres:
IFCT-1003 LADIE trial: Randomized phase II trial evaluating treatment with EGFR-TKI versus EGFR-TKI associated with anti-estrogen in women with non-squamous advanced stage NSCLC.Meeting: 2015 ASCO Annual Meeting | Abstract No: TPS8110
Lung cancer patients with HER2 mutations treated with chemotherapy and HER2 targeted drugs: Results form the EUHER2 cohort study.Meeting: 2015 ASCO Annual Meeting | Abstract No: 11076
- Meeting: 2014 ASCO Annual Meeting | Abstract No: 7526