Lung Cancer

Ceritinib Is Effective in Patients with ALK-Positive NSCLC and Brain Metastases

November 2019 Volume 6 – Lung Cancer
Meg Barbor, MPH

Patients with ALK-positive (ALK+) non–small-cell lung cancer (NSCLC) whose cancer had spread to the brain responded well to the ALK inhibitor ceritinib, regardless of what prior cancer treatment they had received. This research was recently presented at the 2019 European Society for Medical Oncology Congress in Barcelona by Laura Chow, MD, from Dell Medical School at The University of Texas at Austin.

“This is very exciting, and one of the first studies out there to evaluate the efficacy and safety of oral ceritinib in patients with ALK+ NSCLC with active brain metastases,” said Dr. Chow. “Intracranial responses were rapid, high, and durable across all study arms.”

ALK+ lung cancer occurs in about 1 of 25 patients with NSCLC and is more commonly found in younger patients (55 years and under) who have never smoked.

An ALK mutation causes the cells in the lungs to grow abnormally and behave as cancer cells. As these cells continue to grow, they can spread to other parts of the body, including the brain. Drugs called ALK inhibitors work by targeting the ALK+ mutation and stopping the cancer from growing and spreading.

Brain metastases (cancer that originated somewhere else in the body but ultimately spread to the brain) are common in people with ALK+ NSCLC, occurring in up to half of patients.

Treatment of ALK+ NSCLC

Patients with NSCLC and an ALK mutation are commonly treated with crizotinib, but unfortunately, most people develop a resistance to this medication after months or years, and the cancer cells start growing again. When that resistance develops (usually within 1 to 2 years), cancer progression to the brain is frequently reported.

Historically, brain metastases in ALK+ lung cancer are associated with poor outcomes. However, ceritinib, a newer-generation ALK inhibitor, works to overcome that acquired resistance and target the cancer that has spread to the brain.

The ASCEND-7 Trial

The ASCEND-7 study was a phase 2 clinical trial conducted at multiple cancer centers. A phase 2 trial tells doctors more about how safe a cancer treatment is and how well it works.

Unlike other trials in ALK+ NSCLC, this trial was designed specifically to evaluate the effectiveness of ceritinib in patients with ALK+ NSCLC who had newly diagnosed or progressive brain metastases.

Patients were assigned to 1 of 4 study groups: 42 patients previously treated with brain radiotherapy and an ALK inhibitor were assigned to arm 1; 40 patients who had previously received an ALK inhibitor only were assigned to arm 2; 12 patients who received prior brain radiotherapy only were placed in arm 3; and 44 patients who were not previously treated with brain radiotherapy or an ALK inhibitor were assigned to arm 4. The characteristics of patients in each arm were similar in regard to factors like sex, age, smoking status, and performance status.

Ceritinib was given daily, and treatment was continued until patients’ cancer progressed or their side effects were too severe to continue on the trial. Patients received treatment between July 7, 2015, and February 6, 2019.

High Disease Control in All Study Arms

The investigators were pleased to discover that ceritinib was active in all 4 study groups. The drug led to fast, high, and durable intracranial responses across all study arms regardless of prior treatment, with intracranial responses in up to 51.5% of patients who were not previously treated with brain radiotherapy or an ALK inhibitor.

Intracranial response rates were slightly higher in patients who had not been previously treated with an ALK inhibitor like crizotinib, and lower in those who had received an ALK inhibitor, but regardless, the intracranial disease control rate was “exceptionally high” across all the arms, said Dr. Chow.

“Following ceritinib treatment you could see responses in most patients within 2 months,” she added. “The overall response rate was highest in arm 4 with no prior brain radiation or ALK inhibitor, and seemed to be consistent across arms 1, 2, and 3.”

The investigators looked at common study end points like overall response, response duration, and progression-free survival (the length of time during and after treatment that a patient’s cancer does not get worse), and found that ceritinib had a consistent and positive effect.

The side effects of ceritinib were mild, and those severe enough to require patients to quit the study were rare. Most side effects were low-grade diarrhea, nausea, vomiting, elevated liver enzymes, and decreased appetite. According to the researchers, no new or unexpected safety concerns or “surprises” were observed with the use of this drug.

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Last modified: December 6, 2019

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