Real-world treatment of over 1600 Japanese patients with EGFR mutation-positive non-small cell lung cancer with daily afatinib

BACKGROUND: This prospective, post-marketing observational study in Japanese patients aimed to evaluate the safety and effectiveness of daily afatinib use in general practice. METHODS: This non-interventional study (NCT02131259) enrolled treatment-naïve and pre-treated patients with inoperable/recurrent EGFR mutation-positive NSCLC, eligible for afatinib treatment as per the afatinib label in Japan. Patients received afatinib at the approved dose (20, 30, 40, or 50 mg/day; physician decision), and were observed following treatment initiation for 52 weeks or until premature discontinuation. Primary endpoint was the incidence of adverse drug reactions (ADRs). Secondary endpoints included ADRs of special interest, and objective response rate (ORR). Post hoc Cox multivariate analyses were used to assess prognostic factors associated with the incidence of ADRs. RESULTS: 1602 patients, at 374 sites (April 2014–March 2015), were included in the analysis; 307 (19%) were aged ≥ 75 years. The most frequently reported ADRs (all/grade 3–4) were diarrhea (78%/15%), rash/acne (59%/6%), stomatitis (31%/4%), and nail effects (38%/4%). Serious ADRs resulting in death occurred in 18 patients (1%). 762 patients (48%) had ≥ 1 afatinib dose reduction and 366 (23%) discontinued due to ADRs; the most common reason for both was diarrhea (8.2% and 6.7%, respectively). ORR was 40.1%. CONCLUSIONS: Real-world treatment of 1602 Japanese patients with afatinib was associated with a predictable ADR profile. Afatinib showed effectiveness in inoperable/recurrent EGFR mutation-positive NSCLC, especially as first-line treatment. As with other EGFR TKIs, prompt management of adverse events is needed in the Japanese population, to reduce serious events and outcomes, including interstitial lung disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10147-019-01439-5) contains supplementary material, which is available to authorized users.