Evaluation of Ceritinib-Treated Patients (Pts) with Anaplastic Lymphoma Kinase Rearranged (Alk+) Non-Small Cell Lung Cancer (Nsclc) and Brain Metastases in the Ascend-1 Study

Shaw, Alice T.; Mehra, Ranee; Tan, D.S.W.; Felip, Enriqueta; Chow, Laura Q.M.; Camidge, D. Ross; Vansteenkiste, Johan; Sharma, Sunil; Pas, Tommaso De; Riely, Greg J.; Solomon, B.; Wolf, J.; Thomas, Markus; Schüler, Martin; Liu, G.; Santoro, Armando; Geraldes, Margarida; Boral, Anthony; Yovine, Alejandro; Kim, D.

doi:10.1093/annonc/mdu349.72

Cited by 28 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Clinical data support these findings, with ceritinib achieving intracranial activity (11). The efficacy of ceritinib in ALKi-naïve patients and in patients pretreated with crizotinib was first demonstrated in the global pivotal phase I, dose-escalation/dose-expansion ASCEND-1 study (12). Additionally, a phase I study in Japanese patients with ALK+ malignancies (including NSCLC; NCT01634763) showed a tolerable safety profile and clinical activity similar to that reported for ASCEND-1 following treatment with ceritinib (4).…”

Section: Introductionmentioning

confidence: 85%

Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset

Hida

Satouchi

Nakagawa

et al. 2017

Japanese Journal of Clinical Oncology

View full text Add to dashboard Cite

Introduction: Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer is sensitive to tyrosine kinase inhibitors; however, resistance can develop. Data are presented from the phase II trial (ASCEND-2) evaluating efficacy and safety in a subset of Japanese patients with ALKrearranged non-small cell lung cancer previously treated with platinum-based chemotherapy, who experienced disease progression on crizotinib. Methods: Patients with advanced ALK-rearranged non-small cell lung cancer, including those with asymptomatic or neurologically stable baseline brain metastases, received oral ceritinib 750 mg/day. Whole-body and intracranial responses were assessed by investigator and Blinded Independent Review Committee (RECIST v1.1). Safety and tolerability were also investigated. Results: All 24 Japanese patients had received ≥2 previous treatment regimens, with crizotinib the last therapy received prior to ceritinib. Median duration of ceritinib exposure was 8.1 (range: 0.2-12.5) months. Overall response rate was 45.8% (95% confidence interval: 25.6-67.2). Other efficacy endpoints included disease control rate (79.2% [95% confidence interval: 57.8-92.9]), time to response (median 1.9 months [range: 1.7-3.5]), duration of response (median 9.2 months [95% confidence interval: 4.0-not estimable]) and progression-free survival (median 6.6 months [95% confidence interval: 3.7-9.3]). Of the four patients with active baseline target brain lesions, two achieved an intracranial partial response (50%). The most commonly reported adverse events (majority grade 1/2) were nausea (91.7%), diarrhea (83.3%) and vomiting (83.3%). Conclusions: This study demonstrates the clinical activity and manageable tolerability of ceritinib in a Japanese subset of chemotherapy-and crizotinib-pretreated patients with ALK-rearranged non-small cell lung cancer who progressed on crizotinib, as was shown in the whole ASCEND-2 study population. ClinicalTrials.gov identifier: NCT01685060

show abstract

Section: Introductionmentioning

confidence: 85%

Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset

Hida

Satouchi

Nakagawa

et al. 2017

Japanese Journal of Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…In patients treated with ceritinib, the CNS was the first site of progression in 42% of patients who had prior crizotinib therapy, and in 22% of crizotinib-naïve patients [66]. In a small number of patients with measurable brain metastases (n = 24), ceritinib achieved a CNS objective response rate of 29% in the phase I ASCEND-1 study [67]. In the alectinib phase II NP28673 study, 61% of patients had baseline CNS metastases, and in patients with measurable CNS disease at baseline, disease control rate was 85.7% [68].…”

Section: Discussionmentioning

confidence: 99%

The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer

Peters¹,

Bexelius

Munk

et al. 2016

Cancer Treatment Reviews

195

145

View full text Add to dashboard Cite

“…By contrast, in a recent retrospective analysis of ALK-positive patients with measurable brain metastases who were treated with ceritinib on the phase I ASCEND-1 study, the intracranial ORR was 29.2% (20). Beyond CNS activity, next-generation ALK inhibitors have also demonstrated slightly different spectrums of activity against ALK resistance mutations in preclinical models (21)(22)(23).…”

mentioning

confidence: 93%

Alectinib—a new chapter in the management of ALK-positive lung cancer

Gainor

2016

Transl. Lung Cancer Res.

View full text Add to dashboard Cite

Evaluation of Ceritinib-Treated Patients (Pts) with Anaplastic Lymphoma Kinase Rearranged (Alk+) Non-Small Cell Lung Cancer (Nsclc) and Brain Metastases in the Ascend-1 Study

Cited by 28 publications

References 0 publications

Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset

Ceritinib in patients with advanced, crizotinib-treated, anaplastic lymphoma kinase-rearranged NSCLC: Japanese subset

The impact of brain metastasis on quality of life, resource utilization and survival in patients with non-small-cell lung cancer

Alectinib—a new chapter in the management of ALK-positive lung cancer

Contact Info

Product

Resources

About