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Alectinib superior to chemotherapy in advanced ALK+ NSCLC
The Lancet Oncology 19 (6), e285, 2018
Alectinib is more effective than standard chemotherapy in patients with advanced or metastatic anaplastic lymphoma kinase (ALK)- positive nonsmall-cell lung cancer (NSCLC) who have progressed on —or are intolerant to—crizotinib, according to a recent study. In the phase 3 ALUR trial, Silvia Novello (University of Turin, Turin, Italy) and colleagues enrolled 120 patients across 13 countries in Europe and Asia with histologically or cytologically confirmed advanced, recurrent, or metastatic ALK-positive NSCLC, who had received previous treatment with platinum-based doublet chemotherapy and crizotinib. 107 patients were randomised (2: 1) to receive alectinib (600 mg twice daily; n= 72) or chemotherapy (pemetrexed 500 mg/m² or docetaxel 75 mg/m², every 3 weeks; n= 35) until disease progression, withdrawal, or death. The primary endpoint was progression-free survival in the intention-to-treat population; a key secondary endpoint was CNS objective responses in patients with measurable baseline CNS disease. Investigator-assessed median progression-free survival was significantly longer with alectinib than with chemotherapy (9· 6 months [95% CI 6· 9–12· 2] vs 1· 4 months [1· 3–1· 6], hazard ratio [HR] 0· 15; 95% CI 0· 08–0· 29, p< 0· 001). Independent review committee-assessed progression- free survival was consistent with these findings. In patients with measurable baseline CNS disease, a significantly larger proportion achieved an objective CNS response with alectinib (13 [54%] of 24) than with chemotherapy (0 of 16; p< 0· 001). Alectinib also had a favourable safety profile: grade 3 or worse adverse events occurred in 19 (27%) of 70 patients in the alectinib group versus 14 (41%) of 34 in the chemotherapy group.
“Although for first-line treatment of advanced ALK-positive lung cancer alectinib was recently shown to be superior to the old standard crizotinib... a direct comparison with chemotherapy was missing so far,” explained coauthor Jürgen Wolf (University Hospital Cologne, Cologne, Germany).“The ALUR trial now shows a significantly better progression-free survival, CNS efficacy, and tolerability compared to chemotherapy in chemotherapy and crizotinib-pretreated patients.”“We will always need chemotherapy,” commented David Ross Camidge (University of Colorado Denver, Denver, CO, USA),“but the more we understand about a cancer and can target its biology directly, the more we can put off the less personalised, scatter-gun approaches to treatment until later and as later lines of defence.”
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