In a study published in the scientific journal, Lancet Oncology
in March, 2016, senior author Alice Shaw, MD, PhD, of the MGH Thoracic Oncology Program reported results on the treatment of NSCLC patients with documented ALK-genetic alterations who had either never been treated with an ALK inhibitor, or, who had become resistant to the ALK inhibitor crizotinib during treatment, and showed promising results for these patients when treated with another ALK inhibitor- ceritinib. While initially in many NSCLC patients, ALK-rearranged NSCLC responds to crizotinib, eventually tumors become resistant to the drug. Disease progression often involves metastasis to the brain in these patients. In the now completed study, NCT0128516, a phase I trial that recruited 255 patients, aged 18 years and older, between 2011 and 2013 who had ALK-rearranged NSCLC, from 20 academic hospitals in 11 different countries. These were patients who had progressed on standard therapy, or for whom no standard therapy was available. They were treated with oral ceritinib, a more potent ALK inhibitor than crizotinib, and one that also crosses the blood brain barrier to potentially treat brain metastasis. An overall response was reported in 60 (72%) of 83 patients who had never been treated with an ALK inhibitor, and 92 (56%) of 163 patients previously treated with ALK inhibitor. The median duration of response (DOR) was 17 months (95%) in patients who had never been treated with an ALK inhibitor, and an average of 8.3 months in patients previously treated with an ALK inhibitor. Importantly, for 94 NSCLC patients with brain metastasis, intracranial disease control was reported in 15 (79%) of 19 patients who had never been treated with an ALK inhibitor, and in 49 (65%) of 75 patients who had previously been treated with an ALK inhibitor. This study reporting whole body responses as well as intracranial disease control support a clinical benefit for treatment of NSCLC patients with ALK-rearrangements with ceritinib. A phase 2 clinical trial is now underway to confirm these results in additional patients with ALK-rearranged NSCLC, and who may have brain or leptomeningeal metastases.
Source: The Lancet Oncology; 10 March, 2016; Dong-Wan, Kim et al; “Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the mulicentre, open-label, phase 1 trial”