Evaluation of concomitant medications
A concomitant medication was defined as any therapeutic drug used to
manage a comorbid condition in addition to NSCLC between the last visit
and day 1 of EGFR-TKI treatment. All medications administered to every
patient at EGFR-TKI treatment initiation were reviewed. Oral, injection
(e.g., intravenous, intramuscular, and subcutaneous), suppository, and
inhalant medications were included, while as-needed and topical
medications were excluded. PP was defined as five or more concomitant
medications. For compounding agents, we counted each ingredient
separately. PIM use was measured using STOPP ver. 2 criteria,[7] a
screening tool for detecting potentially inappropriate prescribing in
the elderly (age >= 65 years). In addition to PIM-STOPP v2,
we checked PIM use related to EGFR-TKI treatment (PIM-TKI). PIM-TKI was
defined as the use of one of the following: (1) concomitant use of
cytochrome P450 3A4 (CYP3A4) inhibitors/inducers with gefitinib,
erlotinib, or osimertinib[30-32]; (2) concomitant use of CYP1A2
inhibitors with erlotinib[32]; (3) concomitant use of medications
affecting the gastric potential of hydrogen (pH), such as antacids with
gefitinib or erlotinib[30, 32]; and (4) concomitant use of
P-glycoprotein (P-gp) inhibitors/inducers with afatinib[33].