Ceritinib Benefits Patients with ALK-positive NSCLC and Brain Metastases

In patients previously treated with crizotinib for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) and brain metastases, ceritinib treatment elicited clinically meaningful whole-body and intracranial responses with an acceptable tolerability profile. These results were presented at the 2016 European Lung Cancer Conference.1

In this pooled analysis of the 2 ASCEND trials of ceritinib treatment, patients who had been previously treated with crizotinib for ALK-positive NSCLC and had clinically or neurologically stable brain metastases were enrolled. Each day, patients received 750 mg of ceritinib. In the phase 1 ASCEND-1 trial, computed tomography/magnetic resonance imaging (CT/MRI) was performed every 6 weeks, and in the phase 2 ASCEND-2 trial, CT/MRI was performed every 8 weeks.

In ASCEND-1 and ASCEND-2, 98 and 100 patients enrolled, respectively. In ASCEND-1 and ASCEND-2, 69.4% and 72% of patients, respectively, had received previous radiotherapy to the brain. The majority of patients had also received chemotherapy prior to enrolling in the trials.

The primary objectives were efficacy and safety. Pooled analysis of both trials revealed an overall intracranial response of 37.7% (95% CI: 25.6-51.0%) and an intracranial disease control rate (DCR) of 73.8% (95% CI: 60.9-84.2%). Median intracranial duration of response was 12.8 months (95% CI: 6.9 months to nonevaluable).

A blinded independent review committee (BIRC) assessed intracranial response. In total, 61 patients between both trials had measureable baseline lesions. In ASCEND-1, BIRC performed efficacy analyses. In ASCEND-2, Response Evaluation Criteria in Solid Tumors assessed whole-body response. In ASCEND-1 and ASCEND-2, retrospective pooled intracranial responses and prospective pooled cranial responses, respectively, were assessed by BIRC.

The median follow-up for ASCEND-1 was 9.8 months (range: 0.1 to 22.2 months). The overall response rate (ORR) was 41.8% (95% CI: 31.9-52.2%). The DCR was 69.4% (95% CI: 59.3-78.3%). The median duration of response was 8.2 months (95% CI: 5.6-13.1 months). Median progression-free survival (PFS) was 6.7 months (95% CI: 5.4-9.5 months).

The median follow-up for ASCEND-2 was 11.2 months (range: 0.2 to 18.9 months). ORR was 32% (95% CI: 23.0-42.1%); DCR was 64.0% (95% CI: 53.8-73.4%). The median duration of response was 9.3 months (95% CI: 5.5-12.9 months). Median PFS was 6.8 months (95% CI: 5.4-7.4 months).

“BM [brain metastases] are a common site of disease progression in [patients] with ALK+ NSCLC, including those who have received CRZ [crizotinib]. Ceritinib is a selective oral ALK inhibitor with a 20-fold greater potency than CRZ in vitro. Here we present efficacy outcomes in [patients] with CRZ pretreated ALK+ NSCLC and baseline BM, treated with ceritinib in the ASCEND-1 (phase 1) and ASCEND-2 (phase 2) trials,” reported the researchers.

Tolerability was acceptable. Common adverse events (AEs) of any grade in the ASCEND-1 and ASCEND-2 trials, respectively, were diarrhea (76.5% and 82.0%), nausea (83.7% and 82.0%), and vomiting (60.2% and 64.0%). In ASCEND-1, 10 patients discontinued due to an AE, and in ASCEND-2, 7 patients discontinued due to an AE.

Novartis Pharmaceuticals, based in Basel, Switzerland, funded this study.


1. Felip E, Crinò L, Kim D, et al. Whole body and intracranial efficacy of ceritinib in patients (pts) with crizotinib (CRZ) pretreated, ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) and baseline brain metastases (BM): Results from ASCEND-1 and ASCEND-2 trials. Presentation at: IASLC/ESMO European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland. Abstract 141PD.

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