Ceritinib shows therapeutic potential in ALK-positive nonsmall cell lung cancer

The anaplastic lymphoma kinase (ALK) inhibitor ceritinib delivers favourable antitumour activity in ALK-mutated nonsmall cell lung cancer (NSCLC) patients with active brain metastases and/or leptomeningeal disease, according to the phase II ASCEND-7 trial.

ASCEND-7 randomly assigned patients with active brain metastases to the following treatment groups: prior radiotherapy/ALKi-pretreated (arm 1, n=42), no radiotherapy/ALKi-pretreated (arm 2, n=40), prior radiotherapy/ALKi-naïve (arm 3, n=12), or no radiotherapy/ALKi-naïve (arm 4, n=44). Arm 5 (n=18) included patients with leptomeningeal carcinomatosis.

All patients were given ceritinib 750 mg once daily (fasted condition). The primary endpoint was investigator-assessed whole-body overall response rate (ORR), while secondary endpoints included disease control rate (DCR) and intracranial/extracranial responses.

The whole-body ORRs were 35.7 percent (95 percent confidence interval (CI), 21.6–52.0) in arm 1, 30.0 percent (95 percent CI, 16.6–46.5) in arm 2, 50.0 percent (95 percent CI, 21.1–78.9) in arm 3, and 59.1 percent (95 percent CI, 43.2–73.7) in arm 4.

The DCRs were 66.7 percent (95 percent CI, 50.5–80.4) in arm 1, 82.5 percent (95 percent CI, 67.2–92.7) in arm 2, 66.7 percent (95 percent CI, 34.9–90.1) in arm 3, and 70.5 percent (95 percent CI, 54.8–83.2) in arm 4. The corresponding intracranial ORRs were 39.3 percent (95 percent CI, 21.5–59.4), 27.6 percent (95 percent CI, 12.7–47.2), 28.6 percent (95 percent CI, 3.7–71.0), and 51.5 percent (95 percent CI, 33.5–69.2), respectively.

In arm 5, the whole-body ORR was 16.7 percent (95 percent CI, 3.6–41.4) and DCR was 66.7 percent (95 percent CI, 41.0–86.7).

Paired cerebrospinal fluid and plasma sampling revealed that ceritinib penetrated the human blood–brain barrier.