Treatment patterns and survival in patients with ALK- positive non-small-cell lung cancer: a Canadian retrospective study

Abstract

Background: Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase (ALK)-positive (+) non-small-cell lung cancer (nsclc), followed by ceritinib. However, patients eventually progress or develop resistance to crizotinib. With limited real-world data available, the objective of the present work was to evaluate treatment patterns and survival after crizotinib in patients with locally advanced or metastatic ALK+ nsclc in Canada.

Methods: In this retrospective study at 6 oncology centres across Canada, medical records of patients with locally advanced or metastatic ALK+ nsclc were reviewed. Demographic and clinical characteristics, treatments, and outcomes data were abstracted. Analyses focused on patients who discontinued crizotinib treatment.

Results: Of the 97 patients included, 9 were crizotinib-naïve, and 39 were still receiving crizotinib at study end. The 49 patients who discontinued crizotinib treatment were included in the analysis. Of those 49 patients, 43% received ceritinib at any time, 20% subsequently received systemic chemotherapy only (but never ceritinib), and 37% received no further treatment or died before receiving additional treatment. Median overall survival from crizotinib discontinuation was shorter in patients who did not receive ceritinib than in those who received ceritinib (1.7 months vs. 20.4 months, p < 0.001). In a multivariable analysis, factors associated with poorer survival included lack of additional therapies (particularly ceritinib), male sex, and younger age, but not smoking status; patients of Asian ethnicity showed a nonsignificant trend toward improved survival.

Conclusions: A substantial proportion of patients with ALK+ nsclc received no further treatment or died before receiving additional treatment after crizotinib. Treatment with systemic agents was associated with improved survival, with ceritinib use being associated with the longest survival.

Keywords: ALK-positive non-small-cell lung cancer; Crizotinib; ceritinib; lung cancer; survival; treatment patterns.

FIGURE 1

Summary of treatment patterns after crizotinib failure in 49 patients during the study period (2010–2015). In 1 patient, treatment with crizotinib appeared to have been re-instituted; that patient was therefore excluded from the figure. The same patient was also treated with ceritinib after crizotinib. HSP90 = heat shock protein 90.

FIGURE 2

Overall survival from diagnosis in 49 patients experiencing crizotinib failure. Patients were censored if no further data were collected (that is, the date of last data collection occurred before death). Median overall survival was 31.6 months in patients experiencing crizotinib failure.

FIGURE 3

Overall survival starting from diagnosis in 34 patients experiencing crizotinib failure who were initially diagnosed with stage IV non-small-cell lung cancer (NSCLC). Also included are overall survival curves for the same patients, depending on whether they did (n = 11) or did not (n = 23) receive ceritinib treatment (p = 0.003). Patients were censored if no further data were collected (that is, the date of last data collection occurred before death). Median overall survival was 23.6 months for all patients in the cohort; 51.0 months for the group that subsequently received ceritinib; and 18.1 months for the group that did not subsequently receive ceritinib.

FIGURE 4

Overall survival after crizotinib discontinuation for all patients experiencing crizotinib failure. Patients were censored if no further data were collected (that is, the date of last data collection occurred before death). Median overall survival was 1.7 months for patients who received no treatment or treatment without ceritinib, and 20.4 months for patients who received ceritinib (p < 0.0001).

FIGURE 5

Overall survival stratified by treatment received after discontinuation of crizotinib. Patients were censored if no further data were collected (that is, the date of last data collection occurred before death). Median overall survival was 0.9 months in patients who received no treatment after crizotinib, 7.6 months in those who received no ceritinib treatment after crizotinib, and 20.4 months in those who received ceritinib treatment after crizotinib (p < 0.0001).