Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Feb;7(1):100333.
doi: 10.1016/j.esmoop.2021.100333. Epub 2022 Jan 15.

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer

Affiliations
Randomized Controlled Trial

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer

J Wolf et al. ESMO Open. 2022 Feb.

Abstract

Background: At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling.

Patients and methods: Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes.

Results: Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93).

Conclusions: Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.

Keywords: ALK-positive NSCLC; ALUR; TP53; alectinib; chemotherapy.

PubMed Disclaimer

Conflict of interest statement

Disclosure JW has received personal fees and/or grants from Amgen, AstraZeneca (AZ), Bayer, Blueprint, Boehringer Ingelheim (BI), Bristol-Myers Squibb (BMS), Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, Seattle Genetics and Takeda. ÅH has received personal fees and/or grants from AZ, BMS, MSD, Pfizer, Pierre-Fabre, Roche and Takeda. I-JO has received personal fees and/or grants from AZ, BI, BMS, Menarini, MSD, ONO, Pfizer, Roche and Takeda. MRM has received personal fees from AZ, BI, BMS, MSD and Roche. RD has received honoraria or consulting fees from AZ, BI, Clovis Oncology, Novartis, Pfizer, Roche, Foundation Medicine, MSD, Seattle Genetics and Takeda. AW has received travel, accommodation, or expenses from, and participated in speakers' bureaus for BMS, Pfizer, Takeda and Roche. J de C has received personal fees from Amgen, AZ, BI, BMS, Eli Lilly, MSD, Novartis, Pfizer, Roche and Takeda. JM has received personal fees from AZ, BMS, MSD, Novartis, Pfizer and Roche; and grants from AZ and Roche. FG has received personal fees and/or grants from AZ, BI, BMS, Celgene, Chugai, Lilly, MSD, Novartis, Pfizer, Roche and Takeda. MC, AC, TR, KT and VS are employees of F. Hoffmann-La Roche Ltd. TR and KT also own Roche stocks. SN has received personal fees from AMG, AZ, BMS, Eli Lilly, MSD and Roche, and participated in speakers' bureaus for BeiGene, Pfizer, Sanofi and Takeda. Data sharing Qualified researchers may request access to individual patient level data through the clinical study data request platform (https://vivli.org/). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Figures

Figure 1
Figure 1
Kaplan–Meier curves of (A) final investigator-assessed PFS and (B) OS in the ITT population. CI, confidence interval; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival; PFS, progression-free survival.
Figure 2
Figure 2
Maximum change in tumor size from baseline and confirmed response observed in alectinib-treated patients with (A) a non-EML4-ALK fusion detected and (B) a secondary ALK mutation detected in baseline plasma. Figures show best change in tumor size from baseline and tables show confirmed response category at last tumor assessment (as assessed by RECIST v1.1). The response of one patient with a non-EML4-ALK fusion was NE and was therefore excluded from the waterfall plot. ALK, anaplastic lymphoma kinase; CR, complete response; EML4, echinoderm microtubule-associated protein-like 4; NE, not evaluable; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease.
Figure 3
Figure 3
Kaplan–Meier curve of investigator-assessed PFS by baseline TP53 status (WT or mutant) in each treatment arm. PFS, progression-free survival; WT, wild-type.

References

    1. Barlesi F., Mazieres J., Merlio J.P., et al. Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT) Lancet. 2016;387(10026):1415–1426. - PubMed
    1. Tian H.-X., Zhang X.-C., Yang J.-J., et al. Clinical characteristics and sequence complexity of anaplastic lymphoma kinase gene fusions in Chinese lung cancer patients. Lung Cancer. 2017;114:90–95. - PubMed
    1. US Food & Drug Administration (FDA) Alectinib Prescribing Information (PI) 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/208434s004lbl.pdf Available at.
    1. European Medicines Agency (EMA) Alectinib Summary of Product Characteristics (SmPC) https://www.ema.europa.eu/en/documents/product-information/alecensa-epar... Available at.
    1. Hanna N.H., Robinson A.G., Temin S., et al. Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) Joint Guideline Update. J Clin Oncol. 2021;39(9):1040–1091. - PubMed

Publication types

MeSH terms