Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK-Positive Non-Small-Cell Lung Cancer: AF-001JP

J Clin Oncol. 2017 May 10;35(14):1515-1521. doi: 10.1200/JCO.2016.70.5749. Epub 2017 Mar 15.


Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carbazoles / adverse effects
  • Carbazoles / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / chemistry
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Hyperbilirubinemia / chemically induced
  • Lung Neoplasms / chemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / analysis
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Retreatment
  • Survival Rate
  • Symptom Assessment
  • Time Factors


  • Antineoplastic Agents
  • Carbazoles
  • Piperidines
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases
  • alectinib