Afatinib (A) is a selective, orally bioavailable, irreversible ErbB family blocker of EGFR (ErbB1), HER2 (ErbB2) and ErbB4. In a global study investigating the efficacy and safety of A versus cisplatin/pemetrexed (CP) in 345 patients with EGFR mutation-positive advanced lung adenocarcinoma, there was a significantly prolonged progression-free survival (PFS) versus CP (median 11.1 versus 6.9 months, HR 0.58; P = 0.0004) in the overall population and in patients with Ex19del/Ex21L858R mutations (median 13.6 versus 6.9 months, HR = 0.47; P < 0.0001). Here, we present the preplanned analysis of the Japanese subgroup.Methods
As part of a global trial, 83 patients from Japan (stage IIIB/IV, PS 0–1, chemo-naive) were randomized 2:1 (A: 54; CP: 29) to oral daily A 40 mg or IV CP (500 mg/m2 + 75 mg/m2 q21 days up to 6 cycles). Trial primary end point was PFS by central independent review.Results
Baseline characteristics were balanced in both arms: median age, 66 years; female, 69%; never-smoker, 61%; patients with Ex19del/Ex21L858R mutations, 93%. Significant improvement in PFS was observed in the overall Japanese subgroup (median 13.8 versus 6.9 months, HR = 0.38, P = 0.0014), as well as in those with Ex19del/Ex21L858R (HR = 0.28, P < 0.0001). The objective response rate was significantly higher with A (61% versus 21%, P = 0.0007), with a median duration of response of 12.6 versus 4.2 months, respectively. A significant delay in time to deterioration of dyspnea was seen with A versus CP (HR = 0.49, P = 0.0180). Most common drug-related adverse events (AEs) were diarrhea (100%), paronychia (87%) and stomatitis (82%) with A, and nausea (89%), decreased appetite (79%) and neutropenia (71%) with CP. Related AEs suggestive of interstitial lung disease were observed in two patients with A (grade 1 and grade 3). Drug-related AEs led to discontinuation in 15% (A, none for diarrhea) and 25% (CP) of patients.Conclusion
In Japanese patients, treatment with A led to unprecedented prolongation of PFS and improvement in secondary end points compared with CP. Frequency of common AEs in both groups was higher than reported for patients outside of Japan. AEs were manageable and consistent with known safety profiles of both treatments. With 6.9 months improvement in median PFS, afatinib is a clinically relevant first-line treatment option.