Ceritinib Demonstrates Antitumor Activity for ALK-Positive NSCLC With Active Brain Metastases

Patients treated with ceritinib who had ALK-positive non–small cell lung cancer with active brain metastases and/or leptomeningeal disease experienced encouraging responses in the phase 2 ASCEND-7 trial.

Encouraging antitumor activity was observed when patients with ALK-positive non–small cell lung cancer (NSCLC) and active brain metastases and/or leptomeningeal disease were treated with ceritinib (Zykadia), according to results from the phase 2 ASCEND-7 trial (NCT02336451).

Patients with brain metastases were assigned to 1 of 4 arms: those with previous radiation treatment to brain and prior exposure to an ALK inhibitor (arm 1), no previous radiation treatment but prior exposure to an ALK inhibitor (arm 2), previous radiation treatment but no prior ALK inhibitor exposure (arm 3), and no previous radiation treatment nor exposure to an ALK inhibitor (arm 4). A fifth arm was included which encompassed patients leptomeningeal carcinomatosis. Whole-body overall response rates (ORRs) were 35.7% (95% CI, 21.6%-52.0%) in arm 1, 30.0% (16.6%-46.5%) in arm 2, 50.0% (95% CI, 21.1%-78.9%) in arm 3, and 59.1% (43.2%-73.7%) in arm 4.

“Ceritinib treatment achieved clinically meaningfully high and durable response within and outside the brain in patients with ALK-positive NSCLC metastatic to the brain and/or leptomeninges, with higher responses in patients who were ALK inhibitor–naïve,” the investigators wrote. “The intracranial disease control rate was high irrespective of prior ALK inhibitor exposure.”

Eligible patients were aged 18 years or older with ALK-positive NSCLC with active metastases in the brain and/or leptomeninges. Further eligibility criteria included having 1 or more measurable extracranial lesion per RECIST 1.1 and a World Health Organization performance status of 0 to 2.

Patients received 750 mg of oral ceritinib daily, with treatment continuing until disease progression, consent withdrawal, or discontinuation at investigator discretion.

The primary end point was investigator-assessed ORR. Secondary end points included disease control rate (DCR), time to response, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

A total of 156 patients met eligibility criteria when screened between April 2015 and February 2019 and were assigned to arm 1 (n = 42), arm 2 (n = 40), arm 3 (n = 12), arm 4 (n = 44), and arm 5 (n = 18). Median ages across the study arms ranged from 46.0 years to 53.5 years.

Whole-body DCR was highest in arm 2, although DCR was notably high across all study arms. Median investigator-assessed PFS was 7.2 months (95% CI, 3.3-10.9) in arm 1, 5.6 months (95% CI, 3.6-9.2) in arm 2, and 7.9 months (95% CI, 5.5-9.4) in arm 4. Median PFS was not reached in arm 3.

Intracranial ORRs were 39.3% (95% CI, 21.5%-59.4%) in arm 1, 27.6% (95% CI, 12.7%-47.2%) in arm 2, 28.6% (95% CI, 3.7%-71.0%) in arm 3, and 51.5% (95% CI, 33.5%-69.2%) in arm 4.

In arm 5, whole-body ORR was 16.7% (95% CI, 3.6%-41.4%) and DCR was 66.7% (95% CI, 41.0%-86.7%). Further, median PFS was 5.2 months (95% CI, 1.6-7.2) and median OS was 7.2 months (95% CI, 1.6-16.9). Intracranial ORR was 12.5% (95% CI, 0.3%-52.7%).

The most common any grade adverse effects (AEs), defined as occurring in 20% of patients or more, included diarrhea (68.6%), nausea (55.8%), increased alanine aminotransferase (47.4%), vomiting (46.8%), increased aspartate aminotransferase (35.9%), and decreased appetite (32.1%). Grade 3 or 4 AEs were observed in 78.8% of patients, with AEs occurring in more than 10% of patients including increased alanine aminotransferase (28.2%) and increased gamma-glutamyltransferase (16.7%).

Thirty-one (19.1%) on-treatment deaths were reported in this study.

“This study confirmed ceritinib has antitumor activity against treated and un-treated brain metastases in patients with ALK-positive NSCLC with active brain metastases and/or leptomeningeal disease and could be considered in the management of intracranial disease,” the investigators concluded.


Chow LQM, Barlesi F, Bertino EM, et al. ASCEND-7: Efficacy and safety of ceritinib treatment in patients with ALK-positive non-small cell lung cancer metastatic to the brain and/or leptomeninges. Clin Cancer Res. Published online January 28, 2022. doi:10.1158/1078-0432.CCR-21-1838

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