title: Association between time to progression and subsequent survival inceritinib-treated patients with advanced ALK-positive non-small-cell lung cancer.
abstract: Time to progression (TTP) is a surrogate marker of overall survival (OS). However, OS is also dependent on post-progression survival (PPS). This study evaluated the association between TTP and the duration of PPS among adult patients who received ceritinib (Zykadia1) for the treatment of advanced anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC).
  
  
  
  A pooled analysis was performed on 181 ASCEND-1 (phase I) and ASCEND-2 (phase II) patients who experienced disease progression while on ceritinib. TTP was assessed on its association with PPS in a Kaplan-Meier analysis and in Cox proportional hazard models, adjusted for clinical covariates.
  
  
  
  Main outcomes measured include TTP, PPS, and OS.
  
  
  
  Patients with TTP ≥6 months experienced significantly longer PPS compared to those with TTP <6 months (median: 9.8 vs. 6.5 months, log-rank p-value < .01). When TTP was assessed as a continuous variable, every 3 months of longer TTP was associated with a 21% lower hazard of death following progression (hazard ratio [HR]: 0.79, 95% confidence interval [CI]: 0.63-1.00; adjusted HR: 0.79, 95% CI: 0.64-0.99). This positive association translated into an OS benefit: each 3 months of longer TTP was associated with a lower hazard of death (adjusted HR: 0.46, 95% CI: 0.37-0.58). Median OS was 20.0 months for patients with TTP ≥6 months and was 10.9 months for patients with TTP <6 months.
  
  
  
  A longer duration of TTP after treatment with ceritinib was significantly associated with a longer duration of both PPS and OS.
authors.affiliation: a Princess Margaret Cancer Centre , Toronto , ON , Canada.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.affiliation: b Novartis Pharmaceuticals Corporation , East Hanover , NJ , USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: c Analysis Group Inc. , New York , NY , USA.
authors.forename: Zheng-Yi
authors.initials: ZY
authors.lastname: Zhou
authors.affiliation: d Analysis Group Inc. , Boston , MA , USA.
authors.forename: Junlong
authors.initials: J
authors.lastname: Li
authors.affiliation: c Analysis Group Inc. , New York , NY , USA.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Cai
authors.affiliation: d Analysis Group Inc. , Boston , MA , USA.
authors.forename: James
authors.initials: J
authors.lastname: Signorovitch
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013450:Sulfones; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib
keywords: ALK + NSCLC; Ceritinib; Post-progression survival; Time to progression