A Phase IIIb Open-Label, Single-Arm Study of Afatinib in EGFR TKI-Naïve Patients with EGFRm+ NSCLC: Final Analysis, with a Focus on Patients Enrolled at Sites in China

Abstract

Background Afatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutationpositive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in realworld clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies. Objective To report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, "near real-world" study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC. Patients and Methods NCT01953913 was conducted at 34 centers across Asia. Entry criteria were broad to reflect real-world settings. Patients received afatinib 40 mg/day until tumor progression, lack of clinical benefit, or poor tolerability. Assessments included safety, time to symptomatic progression (TTSP), and progression-free survival (PFS). Results 541 patients were treated, of whom 412 were enrolled in China. Dose reductions were implemented in 28.7% of patients overall, and 17.7% of patients from China. Safety findings were consistent with phase III studies of afatinib. Median TTSP in all patients was 14.0 months (95% CI 12.9-15.9), and median PFS was 12.1 months (95% CI 11.0-13.6). Median TTSP (13.8 months, 95% CI 12.7-16.1) and PFS (11.4 months, 95% CI 10.9-13.7) were similar in patients from China to the overall population. Among patients from China who had dose reductions, TTSP was numerically longer than in those who did not (16.4 vs. 13.8 months; P = 0.0703), while PFS was significantly longer (13.9 vs. 11.1 months; P = 0.0275). Among patients from China with brain metastases, TTSP was numerically shorter than in those without (11.0 vs. 14.4 months; P = 0.0869), whereas PFS was significantly shorter (9.2 vs. 12.9 months; P = 0.0075). Conclusions Safety data for afatinib when used in a "near real-world" setting in patients with EGFRm+ NSCLC was consistent with the known safety profile of afatinib. Supporting efficacy data of afatinib were provided in all patients, and in those enrolled in China. Tolerability-guided afatinib dose reduction allowed patients to remain on treatment and continue to experience clinical benefit. Trial Registration Number and Date of Registration NCT01953913 (1 October 2013).Hai-Yan Tu and Jifeng Feng contributed equally to the article.

Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study

“…In a randomized phase II study (LUX-Lung 7), Afatinib showed superior outcomes compared to Gefitinib in advanced NSCLCm+ patients (PFS: 11.0 months vs 10.9 months, HR: 0.73, 95% CI: 0.57-0.95, p = 0.017; ORR: 70% vs 56%, odds ratio (OR): 1.87, 95% CI: 1.18-2.99, p = 0.00083) 18 . A single-arm phase III study conducted in China further confirmed the feasibility of Afatinib as a therapy for Chinese patients with advanced NSCLCm+ (ORR: 59.1%, PFS: 11.4 months) and did not reveal any new safety concerns 19 . Consequently, Afatinib as a neoadjuvant treatment might offer advantages over first-generation EGFR-TKIs for locally advanced NSCLCm+.…”

Overview on Therapeutic Options in Uncommon EGFR Mutant Non-Small Cell Lung Cancer (NSCLC): New Lights for an Unmet Medical Need

“…The exon 20 point mutation pS768I showed a good response to afatinib (a median PFS of 14.7 months) in the trials LUX-lung 2, 3 and 6 [14], and a PFS of 12.3 months in patients treated with osimertinib in a recent trial [61]. One real-world study with afatinib focusing on Chinese patients showed a prevalence of 12% of uncommon mutations; the entire patient population harboring uncommon mutations had a PFS of 9.06 months [64]. A recent large study on a database of 693 EGFR mutant patients harboring 98 different uncommon mutations explored the efficacy of afatinib; the data have been collected from randomized clinical trials and phase IIIb trials, compassionate-use/expanded-access programs, noninterventional trials, case series or case studies [65,66].…”