Oral ceritinib (Zykadia, Novartis) showed efficacy in patients with ALK-positive non-small cell lung cancer (NSCLC) with active brain metastases, according to results from the phase 2 ASCEND-7 study.

Ceritinib, a second-generation ALK inhibitor approved for the treatment of metastatic ALK-positive NSCLC has previously demonstrated promising intracranial antitumor activity. The study, which was presented at the ESMO Congress 2019, specifically evaluated the intracranial effects of ceritinib in patients with active brain metastases.

Brain metastases occur in approximately 30% to 50% of patients with ALK-positive NSCLC and are associated with poor outcomes, according to Laura Q. Chow, MD, who presented the data. Many patients can develop acquired resistance to treatment within 1 to 2 years and frequent progression in the brain has been reported.

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) per 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.

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, according to Chow. Across all study arms, ceritinib achieved fast, high, and durable intracranial responses.

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.

“Although responses have been reported with other second-generation ALK inhibitors, the eligibility criteria were not homogenous across studies,” Chow said in the presentation.

The safety profile in this population was consistent with the reported profile of ceritinib, with no new or unexpected safety concerns observed in the study.

During a discussion of the trial results, Lizza Hendriks, MD, PhD noted that ceritinib performed as expected based on previous ASCEND studies. However, approximately 40% of studies exclude brain metastases, whereas this study included brain metastases and PS2, and leptomeningeal metastases.

“This is really one of the first studies specifically evaluating TKI efficacy across prespecified active BM groups,” Hendriks added. She concluded that more central nervous system metastases-specific TKI trials are needed in order to further understand how to optimize brain metastasis treatment.

Reference
14780 – Results of the ASCEND-7 phase 2 study evaluating ALK inhibitor (ALKi) ceritinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) metastatic to the brain [abstract]. Presented by Laura Q. Chow at ESMO 2019 Congress. September 27, 2019. Barcelona, Spain.