Outcomes in patients with lung cancer treated with crizotinib and erlotinib in routine clinical practice: A post‐authorization safety cohort study conducted in Europe and in the United States

Abstract

Purpose: We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice.Methods: This descriptive cohort study used routinely collected health data in Denmark, Finland, Sweden, the Netherlands, and the United States (US) during 2011-2017, following crizotinib commercial availability in each country. Among crizotinib or erlotinib initiators, we reported baseline characteristics and incidence rates and cumulative incidences of the SOIhepatotoxicity, pneumonitis/interstitial lung disease, QT interval prolongation-related events, bradycardia, vision disorders, renal cysts, edema, leukopenia, neuropathy, photosensitivity, malignant melanoma, gastrointestinal perforation, cardiac failure and OS. Results from the European Union (EU) countries were combined using meta-analysis; results from the US were reported separately.

Cardiovascular disease and lung cancer

“…However, there was a significant difference in baseline characteristics between the EU and USA populations. The prevalence of comorbidities was higher in the USA group ( 49 ). Waliany et al.…”

“…Roughly 5% of patients with NSCLC have anaplastic lymphoma kinase (ALK) gene mutations ( 48 , 49 ). ALK inhibitors (e.g., brigatinib, crizotinib, ceritinib, alectinib) have been in use since 2011 to target NSCLC with ALK mutations ( 48 ).…”

Validation of safety outcomes in routinely collected data: Lessons learned from a multinational postapproval safety study

“…From 2011 to 2017, a regulator‐mandated PASS was conducted to evaluate safety outcomes among patients with primary lung cancer initiating treatment with crizotinib using routinely collected health data in Denmark, Finland, the Netherlands, Sweden, and the USA 5 . In conjunction with this multinational PASS, an nonmandated validation study was conducted to assess the validity of the codes and algorithms used to capture the primary safety outcomes.…”

“…Researchers should also consider more than one validation approach to ensure cases are accurately captured; additionally, procedures for quantifying uncertainty should be explored. 5. Results from validations of case definitions in routinely collected data should be appropriately interpreted in light of how the case definitions were derived.…”

“…3,4 From 2011 to 2017, a regulator-mandated PASS was conducted to evaluate safety outcomes among patients with primary lung cancer initiating treatment with crizotinib using routinely collected health data in Denmark, Finland, the Netherlands, Sweden, and the USA. 5 In conjunction with this multinational PASS, an nonmandated validation study was conducted to assess the validity of the codes and algorithms used to capture the primary safety outcomes. The safety outcomes of interest were QT-prolongation, bradycardia, hepatotoxicity, pneumonitis, and vision disorder, and their identification was based on the routinely collected diagnoses or treatment proxies.…”