Efficacy of Crizotinib among Different Types of ROS1 Fusion Partners in Patients with ROS1-Rearranged Non-Small Cell Lung Cancer.

ROS1 rearrangement-positive NSCLC can be treated effectively with an anaplastic lymphoma kinase/ROS1/mesenchymal-epithelial transition factor inhibitor such as crizotinib; however, the rate of response remains variable. Although several ROS1 fusion partners have been identified, the efficacy of crizotinib in patients with different types of ROS1 fusion partners is poorly understood. We reviewed clinicopathological data of patients with ROS1 rearrangement who received crizotinib therapy at our institution between April 2014 and December 2016. ROS1 fusion partners were evaluated by using Sanger sequencing for available tumor tissue. During the study, 49 patients were found to have ROS1 rearrangement and were subsequently treated with crizotinib. Tumor specimens were available for 36 patients, of whom 19 were found to have CD 74 molecule gene (CD74)-ROS1 fusion partners. Before therapy, those in the CD74-ROS1 group were found to have a higher rate of brain metastases (six versus 0 [p = 0.020]). The objective response rate for crizotinib was 83.3% in all patients, whereas it was 94.11% and 73.68% in the non-CD74-ROS1 and CD74-ROS1 groups, respectively. As compared with the CD74-ROS1 group, the non-CD74-ROS1 group had both a significantly longer progression-free survival (17.63 months versus 12.63 months [p = 0.048]) and a significantly longer overall survival (44.50 months versus 24.33 months [p = 0.036]). On multivariable analysis, the only factor associated with overall survival was presence of brain metastases before therapy (p = 0.010). There were no significant factors associated with progression-free survival in the multivariable analysis. These findings suggests that patients with CD74-ROS1 fusion partners are more likely to present with brain metastases. Although not independently significant, a trend toward improved survival was observed in patients in the non-CD74-ROS1 group when they were treated with crizotinib.

Li Z ，Shen L ，Ding D ，Huang J ，Zhang J ，Chen Z ，Lu S ... -  《-》

Crizotinib vs platinum-based chemotherapy as first-line treatment for advanced non-small cell lung cancer with different ROS1 fusion variants.

ROS1 gene fusion represents a specific subtype of non-small cell lung cancer (NSCLC). Crizotinib is recommended for ROS1-positive NSCLC due to its favorable outcome in published clinical trials. However, due to the low incidence of ROS1-positive NSCLC, there is limited information on real-world clinical outcomes in patients treated with either crizotinib or platinum-based doublet chemotherapy. Outcomes were recorded in 102 patients with stage Ⅲb or Ⅳ NSCLC who were treated at four Chinese hospitals between April, 2010 and June, 2019. Of the 102 patients followed, 71.6% were females, 81.4% were non-smokers, and 98.0% had adenocarcinoma. First-line treatment with crizotinib achieved a significantly longer median progression-free survival (PFS) compared with platinum-based chemotherapy (14.9 months vs 8.5 months, respectively; P < .001). Next-generation sequencing (NGS) identified 61 patients who had ROS1 fusion variants, including CD74 (n = 33) and non-CD74 (n = 28) variants. In patients harboring CD74 fusion variants, the median PFS with first-line crizotinib treatment was significantly longer than in those harboring non-CD74 fusion variants (20.1 months vs 12.0 months, respectively; P = .046). However, in patients treated with platinum-based chemotherapy, there was no significant difference in PFS between the CD74 and non-CD74 variant groups (8.6 months vs 4.3 months, respectively; P = .115). Overall survival (OS) was not reached. First-line therapy with crizotinib is more beneficial than platinum-based chemotherapy in patients with advanced NSCLC with different ROS1 fusion variants. Patients harboring CD74 fusion variants appear to respond better to crizotinib.

Xu H ，Zhang Q ，Liang L ，Li J ，Liu Z ，Li W ，Yang L ，Yang G ，Xu F ，Ying J ，Zhang S ，Wang Y ... -  《Cancer Medicine》

Crizotinib in Chinese Patients with ROS1-Rearranged Advanced Non‒Small-Cell Lung Cancer in Routine Clinical Practice.

Liu C ，Yu H ，Chang J ，Chen H ，Li Y ，Zhao W ，Zhao K ，Zhu Z ，Sun S ，Fan M ，Wang J ... -  《-》

Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial.

ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients.

Michels S ，Massutí B ，Schildhaus HU ，Franklin J ，Sebastian M ，Felip E ，Grohé C ，Rodriguez-Abreu D ，Abdulla DSY ，Bischoff H ，Brandts C ，Carcereny E ，Corral J ，Dingemans AC ，Pereira E ，Fassunke J ，Fischer RN ，Gardizi M ，Heukamp L ，Insa A ，Kron A ，Menon R ，Persigehl T ，Reck M ，Riedel R ，Rothschild SI ，Scheel AH ，Scheffler M ，Schmalz P ，Smit EF ，Limburg M ，Provencio M ，Karachaliou N ，Merkelbach-Bruse S ，Hellmich M ，Nogova L ，Büttner R ，Rosell R ，Wolf J ... -  《-》

Treatment Patterns and Clinical Outcomes Among Patients With ROS1-rearranged Non-small-cell Lung Cancer Progressing on Crizotinib.

De Giglio A ，Lamberti G ，Facchinetti F ，Genova C ，Andrini E ，Dal Bello MG ，Tiseo M ，Metro G ，Chiari R ，Ricciuti B ... -  《-》