Ceritinib in ALK+ NSCLC brain metastases

Oral ceritinib showed efficacy in patients with ALK-positive non-small cell lung cancer (NSCLC) that has metastasised to the brain, according to results from the phase 2 ASCEND-7 study presented by Dr Laura Quan Man Chow (University of Texas at Austin, USA) [1].

As the prognosis of patients with ALK-positive NSCLC improves, so does the likelihood of developing leptomeningeal disease; brain metastases occur in approximately 30% to 50% of patients with ALK-positive NSCLC and are associated with poor outcomes, according to Dr Chow. The phase 2 ASCEND-7 trial results demonstrated that ceritinib was effective in controlling leptomeningeal metastasis in patients with ALK-positive NSCLC.

The study treatment arms were divided based on prior treatment with radiotherapy and ALK inhibitors, with a primary endpoint of investigator-assessed whole body overall response rate (ORR) according to RECIST 1:1. Treatment arms included prior brain radiotherapy and prior ALK inhibitor (Arm 1), no prior brain radiotherapy and prior ALK inhibitor (Arm 2), prior brain radiotherapy and no prior ALK inhibitor (Arm 3), and no prior brain radiotherapy and no prior ALK inhibitor (Arm 4). Across all 4 arms, median follow-up was 5.49 months for a total of 138 patients. The main results are shown in the Table.

The safety profile in this population was consistent with the reported profile of ceritinib, with no new or unexpected safety signals observed in the study. Regardless of prior ALK inhibitor treatment, ceritinib activity was consistent with its known efficacy established in patients with ALK-positive NSCLC with or without brain metastases. Across all study arms, ceritinib achieved fast, high, and durable intracranial responses. Dr Chow also noted that patients who were naïve to a previous ALK inhibitor had higher intracranial response and intracranial disease control rate was high across all arms.

Table. Results of the ASCEND-7 trial

‡L is the number of patients included in the duration of response analysis. M, number of patients with measurable brain metastases at baseline DCR, disease control rate; DOR, duration of response; NE, not estimable; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.

1. Chow LQ et al. ESMO Congress 2019. Abstract 14780.

Posted on 26 November 201925 March 2024