ASCO: Ceritinib shrank tumors in most patients with ALK+ NSCLC regardless of prior ALK treatment

Ceritinib (Zykadia) previously known as LDK378, shrank tumors in patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC), including those who had received previous treatment with an ALK inhibitor as well as patients receiving one for the first time, according to data presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago. Results were also observed in patients with ALK+ NSCLC who entered the study with brain metastases.

The phase 1 single-arm study evaluated 246 patients with ALK+ NSCLC who received ceritinib 750 mg daily and had a 7-month median duration of follow-up.  Of these 246 patients, 166 (67%) had received at least 2 prior regimens and 163 (66%) had been previously treated with an ALK inhibitor.

The data showed that among 163 patients receiving 750 mg of ceritinib daily and who were previously treated with crizotinib, ORR was 54.6% [95% CI, 46.6-62.4%] and PFS was 6.9 months [95% CI, 5.4-8.4 months]. The most common adverse events, occurring in more than half of patients, were diarrhea, nausea, vomiting, abdominal pain and fatigue.

“Disease progression is often inevitable for NSCLC patients whose tumor is driven by a rearrangement in the ALK gene,” said Margaret Dugan, senior VP global program head at Novartis Oncology.  “Most patients with ALK+ NSCLC are relatively young on average, with a rare smoking history. These patients may relapse less than a year after beginning initial therapy with crizotinib and in the United States.”

“Based on this analysis in additional ALK+ NSCLC patients with longer follow-up, ceritinib continues to demonstrate consistent activity in this patient population,” Dugan said. “Specifically, this study showed that ceritinib had a high level of activity in patients with ALK+ NSCLC regardless of whether or not they were previously treated with an ALK inhibitor.”

Another noteworthy finding in this study population is that ceritinib exhibited activity among patients whose cancer had metastasized to the brain, which is currently one of the biggest challenges in treating ALK+ NSCLC, according to Dugan.

NSCLC is the most common type of lung cancer, accounting for 85% to 90% of all cases, and approximately 2% to 7% of patients with NSCLC have the ALK gene rearrangement.

“These patients may relapse less than a year after beginning initial therapy with crizotinib and [ceritinib] addresses an unmet medical need for these patients,” Dugan said.

Ceritinib is the first FDA-approved therapy for patients with ALK+ NSCLC who have progressed following treatment with crizotinib, addressing an unmet medical need for patients with this type of lung cancer. This data presented at ASCO was sponsored by Novartis.