Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study
Mené sur 107 patients atteints d'un cancer du poumon non à petites cellules ALK+ de stade avancé ou métastatique, cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'alectinib et d'une chimiothérapie (pémétrexed ou docétaxel) après l'échec d'une chimiothérapie à base de sels de platine et d'un traitement par crizotinib
Background : This is the first trial to directly compare efficacy and safety of alectinib versus standard chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) patients who have progressed on, or were intolerant to, crizotinib. Patients and methods : ALUR (MO29750; NCT02604342) was a randomized, multicenter, open-label, phase III trial of alectinib versus chemotherapy in advanced/metastatic anaplastic lymphoma kinase (ALK)-positive NSCLC patients previously treated with platinum-based doublet chemotherapy and crizotinib. Patients were randomized 2:1 to receive alectinib 600 mg twice daily or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, both every 3 weeks) until disease progression, death, or withdrawal. Primary endpoint was investigator-assessed progression-free survival (PFS). Results : Altogether, 107 patients were randomized (alectinib, n=72; chemotherapy, n=35) in 13 countries across Europe and Asia. Median investigator-assessed PFS was 9.6 months (95% confidence interval [CI]: 6.9–12.2) with alectinib and 1.4 months (95% CI: 1.3–1.6) with chemotherapy (hazard ratio 0.15 [95% CI: 0.08–0.29]; P<0.001). Independent Review Committee-assessed PFS was also significantly longer with alectinib (HR 0.32 [95% CI: 0.17–0.59]; median PFS was 7.1 months [95% CI: 6.3–10.8] with alectinib and 1.6 months [95% CI: 1.3–4.1] with chemotherapy). In patients with measurable baseline central nervous system (CNS) disease (alectinib, n=24; chemotherapy, n=16), CNS objective response rate was significantly higher with alectinib (54.2%) versus chemotherapy (0%; P<0.001). Grade ≥3 adverse events (AEs) were more common with chemotherapy (41.2%) than alectinib (27.1%). Incidence of AEs leading to study-drug discontinuation was lower with alectinib (5.7%) than chemotherapy (8.8%), despite alectinib treatment duration being longer (20.1 versus 6.0 weeks). Conclusion : Alectinib significantly improved systemic and CNS efficacy versus chemotherapy for crizotinib-pretreated ALK-positive NSCLC patients, with a favorable safety profile.Trial registrationClinicalTrials.gov NCT02604342; Roche study MO29750
Annals of Oncology 2018