Evidence Accumulates For Ceritinib Activity In Heavily Pretreated ALK-Rearranged NSCLC

Patients with ALK-rearranged non-small-cell lung cancer refractory to crizotinib may benefit from ceritinib

medwireNews: ASCEND-2 trial results add support to the use of the ceritinib in patients with ALK-rearranged non-small-cell lung cancer (NSCLC) who have previously been treated with crizotinib .

The phase II trial results are “generally consistent” with the initial ASCEND-1 findings indicating that the ALK inhibitor has efficacy in heavily pretreated patients, even those with brain metastases, say Lucio Crinò, from University Medical School of Perugia in Italy, and co-workers.

The current study, which is published in the Journal of Clinical Oncology, included 140 patients who had received at least one line of platinum-based chemotherapy and progressed while using the ALK inhibitor crizotinib.

After a median 8.8 months of ceritinib therapy and 11.3 months of follow-up, the RECIST-defined whole-body overall response rate in the 140 patients was 38.6%, with 2.9% achieving a complete response, 35.7% a partial response and 38.6% stable disease. Progressive disease occurred in 13.6% and response was unknown in 9.3%.

One hundred of the patients had brain metastases at baseline; the overall whole-body response rate for this subgroup was 33.0%, with 33.0% achieving partial response, 41.0% stable disease and 16.0% experiencing progression. Response was unknown in 10.0%.

Intracranial response was determined in 20 patients, showing a complete response in 10.0%, a partial response in 35.0% and stable disease in 35.0%, with just 15.0% experiencing intracranial disease progression. This gave an overall intracranial response rate of 45.0% and an intracranial disease control rate of 80.0%.

Overall survival was assessed in 81 patients, giving a median of 14.9 months, with 12-month survival achieved by 63.8% of the group; 51.4% of the patients were alive at time of data cutoff.

Grade 3 and 4 adverse events occurred in 71.4%, with 45.7% of events suspected of being drug-related, most commonly elevated alanine aminotransferase and γ-glutamyltransferase affecting 17.1% and 12.1% of patients, respectively.

Any-grade pneumonitis and QTc prolongation were reported in 1.4% and 7.9% of patients, respectively, with 0.7% experiencing grade 4 of these side effects. There were no grade 3 or 4 reports of hyperglycaemia or bradycardia.

Over 90% of patients completed patient-reported outcome (PRO) assessments over the course of the study and these showed no worsening of cancer symptoms during treatment and a trend towards improvements in cough, pain and dyspnoea.

Health-related quality of life during treatment was “generally maintained” despite patients experiencing more nausea, vomiting and diarrhoea than at baseline, although the researchers admit their single-arm data for PROs without a comparator treatment should be “considered with caution”.

The authors conclude: “These results support the positive benefit-risk profile of ceritinib compared with currently available therapies in patients with ALK-rearranged NSCLC who have experienced progression during crizotinib treatment.”


Crinò L, Ahn M-J, De Marinis F, et al. Multicenter phase II study of whole-body and intracranial activity with ceritinib in patients with ALK-rearranged non-small-cell lung cancer previously treated with chemotherapy and crizotinib: Results from ASCEND-2. J Clin Oncol 2016; Advance online publication 18 July. doi: 10.1200/JCO.2015.65.5936

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