Continuation of ceritinib therapy beyond disease progression was associated with prolonged survival, according to results from a retrospective study of the use of ceritinib to treat advanced ALK-positive non-small cell lung cancer (NSCLC). These results were presented at the 2016 European Lung Cancer Conference.1
Ceritinib has an acceptable tolerability profile and is efficacious in the treatment of advanced ALK-positive NSCLC previously treated with crizotinib. Patients who develop progressive disease after ceritinib treatment, however, have limited treatment options. This study examined whether continued ceritinib treatment beyond response evaluation criteria in solid tumors (RECIST)-defined progression of disease correlated with prolonged postprogression survival (PPS).
This retrospective study examined data from patients pretreated with crizotinib who experienced RECIST-defined disease progression. The data came from 2 single-arm clinical trials of ceritinib, ASCEND-1 and ASCEND-2. This study defined continuation of ceritinib as more than 21 days of ceritinib therapy after disease progression.
Among 181 patients who experienced disease progression, 99 (55%) continued ceritinib treatment. A higher percentage of patients who continued ceritinib had ECOG score 0/1 (97% vs 85%) and brain metastases (77% vs 63%) compared with patients who stopped ceritinib.
Patients who continued ceritinib treatment experienced significantly longer PPS than those who discontinued the drug at disease progression (median: 12.0 vs 4.2 months, log-rank P = 21 days; hazard ratio (HR): 0.47, and ≥6 months, HR: 0.35).
This study used Cox proportional hazard models to assess associations with PPS. Cox proportional hazard models were adjusted for patient characteristics such as age, sex, race, body mass index, number of prior regimens, tumor histology, presence of brain metastases at screening, last known ECOG performance score prior to/at progression, whether progression was due to a new lesion, best response prior to progression, and time to progression.
Further studies with larger sample sizes could be useful for validating these results. Novartis Pharmaceuticals, based in Basel, Switzerland, funded this study.
1. Tan D, Liu G, Kim D, et al. Continuation of ceritinib beyond disease progression is associated with prolonged post-progression survival (PPS) in ALK+ NSCLC. Presentation at: IASLC/ESMO European Lung Cancer Conference 2016; April 13-16, 2016; Geneva, Switzerland. Abstract 178P.