Crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC). Preliminary results of the ACSé phase II trial.

Moro‐Sibilot, D.; Faivre, Laurence; Zalcman, Gérard; Pérol, Maurice; Otto, Josiane; Monnet, I.; Cortot, A.; Wislez, Marie; Durando, Xavier; Lantuéjoul, Sylvie; Rouquette, Isabelle; Florin, Anne; Ferretti, Gilbert; Labouret, Natalie Hoog; Nowak, Frédérique; Jimenez, Marta; Vassal, Gilles

doi:10.1200/jco.2015.33.15_suppl.8065

Cited by 48 publications

(31 citation statements)

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“…In the phase I PROFILE 1001, enrolling 50 patients with ROS1-positive NSCLC, objective response rate (ORR) was 72% and median progressionfree survival (PFS) exceeded 19 months (10). These results mirror those observed in ALK-positive NSCLC and are comparable with what was reported in subsequent retrospective and prospective trials (11)(12)(13)(14)(15). At present, crizotinib has a well-established role in ROS1-positive NSCLC and is available worldwide.…”

Section: Introductionsupporting

confidence: 88%

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Landi

Chiari

Tiseo

et al. 2019

Clinical Cancer Research

152

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Purpose: MET-deregulated NSCLC represents an urgent clinical need because of unfavorable prognosis and lack of specific therapies. Although recent studies have suggested a potential role for crizotinib in patients harboring MET amplification or exon 14 mutations, no conclusive data are currently available. This study aimed at investigating activity of crizotinib in patients harboring MET or ROS1 alterations.Patients and Methods: Patients with pretreated advanced NSCLC and evidence of ROS1 rearrangements (cohort A) or MET deregulation (amplification, ratio MET/CEP7 >2.2 or MET exon 14 mutations, cohort B) were treated with crizotinib 250 mg twice daily orally. The coprimary endpoint was objective response rate in the two cohorts.Results: From December 2014 to March 2017, 505 patients were screened and a total of 52 patients (26 patients per cohort) were enrolled onto the study. At data cutoff of September 2017, in cohort A, objective response rate was 65%, and median progression-free survival and overall survival were 22.8 months [95% confidence interval (CI) 15.2-30.3] and not reached, respectively. In cohort B, objective response rate was 27%, median progression-free survival was 4.4 months (95% CI 3.0-5.8), and overall survival was 5.4 months (95% CI, 4.2-6.5). No difference in any clinical endpoint was observed between MET-amplified and exon 14-mutated patients. No response was observed among the 5 patients with cooccurrence of a second gene alteration. No unexpected toxicity was observed in both cohorts.Conclusions: Crizotinib induces response in a fraction of MET-deregulated NSCLC. Additional studies and innovative therapies are urgently needed.

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Section: Introductionsupporting

confidence: 88%

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Landi

Chiari

Tiseo

et al. 2019

Clinical Cancer Research

152

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“…Furthermore, ORR with crizotinib was 80 % and median PFS was 9.1 months in heavily pre-treated patients in a retrospective study [27]. Consistent with this, in patients with advanced ROS1 -positive NSCLC receiving crizotinib in a French phase 2 trial, ORR was 69 % and median PFS was 9.1 months [28]. Finally, ORR was 69 % and median PFS was 12.9 months with crizotinib in a phase 2 trial in East Asian patients with advanced ROS1 -positive NSCLC [29].…”

Section: Efficacy and Safety Of Ros1 Inhibitor Therapymentioning

confidence: 67%

Testing for ROS1 in non-small cell lung cancer: a review with recommendations

et al. 2016

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Rearrangements of the ROS1 gene occur in 1–2 % of non-small cell lung cancers (NSCLCs). Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC. Consequently, focus on ROS1 testing is growing. Most laboratories currently rely on fluorescence in situ hybridisation (FISH) assays using a dual-colour break-apart probe to detect ROS1 rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing. Non-in situ testing approaches also hold potential as stand-alone methods or complementary tests, including multiplex real-time PCR assays and next-generation sequencing (NGS) platforms which include commercial test kits covering a range of fusion genes. In order to ensure high-quality biomarker testing, appropriate tissue handling, adequate control materials and participation in external quality assessment programmes are essential, irrespective of the testing technique employed. ROS1 testing is often only considered after negative tests for EGFR mutation and ALK gene rearrangement, based on the assumption that these oncogenic driver events tend to be exclusive. However, as the use of ROS1 inhibitors becomes routine, accurate and timely detection of ROS1 gene rearrangements will be critical for the optimal treatment of patients with NSCLC. As NGS techniques are introduced into routine diagnostic practice, ROS1 fusion gene testing will be provided as part of the initial testing package.

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“…On the basis of these striking results, crizotinib was granted full approval in the spring of 2016 by the FDA for treatment of advanced ROS1 -rearranged lung cancer and remains to date the only approved treatment for this molecularly defined subset. Two subsequent studies from Europe have demonstrated PFS about half of that originally described for crizotinib in PROFILE 1001, in the 9-10-month range (9,10). However, it should be noted that for both of these studies, the number of patients evaluated was low (<30), and the EUROS1 study was retrospective (Table 1).…”

mentioning

confidence: 83%

Targeting ROS1 rearrangements in non-small cell lung cancer with crizotinib and other kinase inhibitors

Sehgal¹,

Patell²,

Rangachari³

et al. 2018

Transl. Cancer Res

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Crizotinib in patients with advanced ROS1-rearranged non-small cell lung cancer (NSCLC). Preliminary results of the ACSé phase II trial.

Cited by 48 publications

References 0 publications

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Crizotinib inMET-Deregulated orROS1-Rearranged Pretreated Non–Small Cell Lung Cancer (METROS): A Phase II, Prospective, Multicenter, Two-Arms Trial

Testing for ROS1 in non-small cell lung cancer: a review with recommendations

Targeting ROS1 rearrangements in non-small cell lung cancer with crizotinib and other kinase inhibitors

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