Abstract
BackgroundThis prospective, post-marketing observational study in Japanese patients aimed to evaluate the safety and effectiveness of daily afatinib use in general practice.MethodsThis 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.Results1602 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%.ConclusionsReal-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.
Highlights
Mutations of the epidermal growth factor receptor (EGFR) gene are important drivers of non-small cell lung cancer (NSCLC)
Afatinib was previously assessed in two pivotal phase 3 trials: LUX-Lung 3 and LUX-Lung 6, which showed that afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with treatment-naïve EGFR mutation-positive NSCLC [3, 4]
In a pre-planned subgroup analysis of Japanese patients in LUX-Lung 3, PFS was found to be significantly longer with afatinib than with cisplatin/pemetrexed [median 13.8 versus 6.9 months; hazard ratio (HR), 0.38, 95% confidence interval (CI) 0.20–0.70; p = 0.0014], with more pronounced improvements among patients with common mutations (Del19/L858R: HR, 0.28, 95% CI 0.15–0.52; p < 0.0001) and Del19 mutations (HR, 0.16, 95% CI 0.06–0.39; p < 0.0001)
Summary
Mutations of the epidermal growth factor receptor (EGFR) gene are important drivers of non-small cell lung cancer (NSCLC). Afatinib was previously assessed in two pivotal phase 3 trials: LUX-Lung 3 (conducted globally) and LUX-Lung 6 (conducted in China, Thailand and South Korea), which showed that afatinib significantly improved progression-free survival (PFS) versus chemotherapy in patients with treatment-naïve EGFR mutation-positive NSCLC [3, 4]. The incidence of interstitial lung disease (ILD) is higher in Japan than in other countries, and in LUXLung 3, a higher frequency of adverse events was reported in the Japanese subgroup than in the overall trial population [3, 6, 9,10,11,12] We, initiated this prospective, post-marketing observational study to evaluate the safety and effectiveness of daily afatinib used in day-to-day clinical practice in Japan. In accordance with the Japanese Good Post-Marketing Study Practice (GPSP) regulations, all patients treated with afatinib were enrolled in the study, including both EGFR TKI-naïve and EGFR TKI-pre-treated patients, eliminating the selection bias seen in randomized clinical trials
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