Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer

Solange Peters, D Ross Camidge, Alice T Shaw, Shirish Gadgeel, Jin S Ahn, Dong-Wan Kim, Sai-Hong I Ou, Maurice Pérol, Rafal Dziadziuszko, Rafael Rosell, Ali Zeaiter, Emmanuel Mitry, Sophie Golding, Bogdana Balas, Johannes Noe, Peter N Morcos, Tony Mok, ALEX Trial Investigators, Marco Platania

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease.

METHODS: In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily). The primary end point was investigator-assessed progression-free survival. Secondary end points were independent review committee-assessed progression-free survival, time to CNS progression, objective response rate, and overall survival.

RESULTS: During a median follow-up of 17.6 months (crizotinib) and 18.6 months (alectinib), an event of disease progression or death occurred in 62 of 152 patients (41%) in the alectinib group and 102 of 151 patients (68%) in the crizotinib group. The rate of investigator-assessed progression-free survival was significantly higher with alectinib than with crizotinib (12-month event-free survival rate, 68.4% [95% confidence interval (CI), 61.0 to 75.9] with alectinib vs. 48.7% [95% CI, 40.4 to 56.9] with crizotinib; hazard ratio for disease progression or death, 0.47 [95% CI, 0.34 to 0.65]; P<0.001); the median progression-free survival with alectinib was not reached. The results for independent review committee-assessed progression-free survival were consistent with those for the primary end point. A total of 18 patients (12%) in the alectinib group had an event of CNS progression, as compared with 68 patients (45%) in the crizotinib group (cause-specific hazard ratio, 0.16; 95% CI, 0.10 to 0.28; P<0.001). A response occurred in 126 patients in the alectinib group (response rate, 82.9%; 95% CI, 76.0 to 88.5) and in 114 patients in the crizotinib group (response rate, 75.5%; 95% CI, 67.8 to 82.1) (P=0.09). Grade 3 to 5 adverse events were less frequent with alectinib (41% vs. 50% with crizotinib).

CONCLUSIONS: As compared with crizotinib, alectinib showed superior efficacy and lower toxicity in primary treatment of ALK-positive NSCLC. (Funded by F. Hoffmann-La Roche; ALEX ClinicalTrials.gov number, NCT02075840 .).

Original languageEnglish
Pages (from-to)829-838
Number of pages10
JournalNew England Journal of Medicine
Volume377
Issue number9
DOIs
Publication statusPublished - Aug 31 2017

Keywords

  • Adult
  • Aged, 80 and over
  • Animals
  • Antineoplastic Agents
  • Carbazoles
  • Carcinoma, Non-Small-Cell Lung
  • Central Nervous System Neoplasms
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Lung Neoplasms
  • Male
  • Middle Aged
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Receptor Protein-Tyrosine Kinases
  • Young Adult
  • Clinical Trial, Phase III
  • Comparative Study
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

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