ESMO 2016: Ceritinib Provides Longer Progression-Free Survival Than Chemotherapy in Phase III Trial of ALK-Rearranged Lung Cancer Treatment
Ceritinib (Zykadia) provides longer progression-free survival than chemotherapy in crizotinib–pretreated patients with non–small cell lung cancer harboring an ALK rearrangement, according to results of the phase III ASCEND-5 study presented by Scagliotti et al at the European Society for Medical Oncology (ESMO) 2016 Congress in Copenhagen (Abstract LBA42_PR).
“Patients with non–small cell lung cancer (NSCLC) should receive front-line therapy with the anaplastic lymphoma kinase (ALK) inhibitor crizotinib [Xalkori],” said lead author Giorgio Scagliotti, MD, PhD, Head of the Department of Oncology at the University of Turin, Italy. “Most patients develop resistance to crizotinib, and currently, second-line treatment is represented by chemotherapy alone.”
He continued, “This was the first phase III study to assess whether the second-generation ALK inhibitor ceritinib was superior to chemotherapy upon progression on crizotinib therapy in NSCLC.”
ASCEND-5
The open-label ASCEND-5 study included 231 patients with NSCLC who had received crizotinib. Patients were randomized 1:1 to receive therapy with ceritinib or chemotherapy (pemetrexed [Alimta] or docetaxel). Patients who discontinued chemotherapy due to disease progression could cross over to treatment with ceritinib. The primary endpoint was progression-free survival, assessed by a blinded independent review committee.
Median progression-free survival was significantly improved with ceritinib compared to chemotherapy (5.4 vs 1.6 months, hazard ratio [HR] = 0.49, P < .001). Ceritinib increased overall response rate compared to chemotherapy (39.1% vs 6.9%). There was no improvement in overall survival with ceritinib compared to chemotherapy.
Of the patients who discontinued chemotherapy due to disease progression, 75 crossed over to ceritinib.
Dr. Scagliotti said, “Progression-free survival was significantly lengthened with ceritinib compared to chemotherapy. We did not observe an improvement in overall survival with ceritinib, probably because the patients who crossed over diluted the potential benefit.”
Patients taking ceritinib had similar toxicities to those observed in phase I and II studies. The most frequent grade 3/4 adverse events with ceritinib were nausea (7.8%), vomiting (7.8%), and diarrhea (4.3%). With chemotherapy, the most common adverse events were neutropenia (15.5%), fatigue (4.4%), and nausea (1.8%). Ceritinib significantly improved patient-reported outcomes, including lung cancer-specific symptoms and overall health status, compared to placebo (P < .05).
“This study opens up a new treatment paradigm after crizotinib failure,” said Dr. Scagliotti. “It would be logical now to give a sequence of active drugs, starting with crizotinib in the first-line setting and moving to ceritinib in the second line.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
