Alectinib

ALUR was a randomized, open-label, phase III trial. Patients were randomized 2 : 1 to receive alectinib 600 mg twice daily, or chemotherapy (pemetrexed 500 mg/m² or docetaxel 75 mg/m², every 3 weeks, at the investigators’ discretion) until disease progression, death, or withdrawal. Randomization was carried out using the following stratification factors: ECOG PS (0/1 versus 2); baseline CNS metastases (yes/no); and, for patients with baseline CNS metastases, brain radiotherapy history (yes/no). Crossover from chemotherapy to alectinib was permitted following progression. At the investigators’ discretion, alectinib could be continued beyond radiologic progression until loss of clinical benefit. The primary analysis cutoff was 26 January 2017, when the sponsor became aware of 50 PFS events. Additional information regarding the study design is in the supplementary material, available at Annals of Oncology online.
Primary end point was investigator-assessed PFS with alectinib versus chemotherapy in the intent-to-treat (ITT) population. A key secondary end point was CNS objective response rate (ORR) in patients with measurable baseline CNS disease. Other secondary end points included: Independent Review Committee (IRC)-assessed PFS; ORR, disease control rate (DCR), and duration of response (DOR; investigator- and IRC-assessed); time to CNS progression by baseline CNS disease; CNS DCR and CNS DOR in patients with baseline CNS metastases; overall survival (OS); safety. CNS end points were IRC-assessed. The supplementary material, available at Annals of Oncology online provides end point definitions.
ALUR was undertaken in accordance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. The protocol was approved by institutional review boards/ethics committees at each participating site. Written informed consent was obtained from all patients.

Patients received continuing alectinib treatment from the time of disease progression on prior alectinib until repeated disease progression, an unacceptable adverse event (AE), or death occurred. If necessary, additional systemic or local therapies were administered concurrently with alectinib treatment.

PFS was considered to be the time to progression or death following initial progression with alectinib. OS was calculated from the initiation of alectinib treatment to the time of death. ORR was considered to be the ORR during the continuation of alectinib. Kaplan-Meier survival curves were generated for PFS and OS. The “swimplot” package and “ggplot” package in R software were used for creating swim plots. All statistical analyses were conducted using R software version 4.2.3 and Jamovi software version 2.3.18 for Microsoft Windows 64.