A phase II double-blind study to investigate efficacy and safety of two doses of the triple angiokinase inhibitor BIBF 1120 in patients with relapsed advanced non-small-cell lung cancer

Abstract

Background: To assess the efficacy, safety, tolerability and pharmacokinetics of BIBF 1120 in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC).Methods: Patients with locally advanced or metastatic relapsed NSCLC in whom first-or second-line platinumbased chemotherapy failed were randomly allocated to daily 250 mg BIBF 1120 b.i.d. or 150 mg BIBF 1120 b.i.d. Primary end points were progression-free survival (PFS) and objective tumour response (RECIST). Incidence and severity of adverse events (AEs) were reported.Results: Seventy-three patients received BIBF 1120. Median PFS was 6.9 weeks, with no significant difference between treatment arms. Median overall survival (OS) was 21.9 weeks. Eastern Cooperative Oncology Group (ECOG) 0-1 patients (n = 56) had a median PFS of 11.6 weeks and a median OS of 37.7 weeks. Tumour stabilisation was achieved in 46% of patients (ECOG 0-1 patients: 59%), with one confirmed partial response (250 mg b.i.d.). Most commonly reported drug-related AEs were nausea (57.5%), diarrhoea (47.9%), vomiting (42.5%), anorexia (28.8%), abdominal pain (13.7%) and reversible alanine transaminase (13.7%) and aspartate aminotransferase elevations (9.6%). BIBF 1120 displayed dose-linear pharmacokinetic characteristics. Conclusion:Continuous treatment with BIBF 1120 was well tolerated, with no difference in efficacy between treatment arms. PFS and objective response with single-agent treatment in advanced disease warrants further exploration.

Phase I Open-Label Study of Continuous Treatment with BIBF 1120, a Triple Angiokinase Inhibitor, and Pemetrexed in Pretreated Non–Small Cell Lung Cancer Patients

“…Due to the small sample size of 26 patients treated with BIBF 1120, it is difficult to conclude whether this low frequency is a result by chance. However, this observation is in line with the safety data from other phase I and phase II trials of BIBF 1120 (16,17,21,22).…”

Carboplatin plus paclitaxel in combination with bevacizumab for the treatment of adenocarcinoma with interstitial lung diseases

“…Compared with placebo in IPF patients, high-dose BIBF1120 was found to inhibit the decrease in lung function and was associated with fewer acute exacerbations (10). A clinical trial comparing 250 and 150 mg BIBF1120 twice daily in NSCLC patients unresponsive to platinum drugs did not show a difference in PFS (11). However, a study assessing the combination of docetaxel (12) or pemetrexed (13) and BIBF1120 is currently being conducted.…”

Перспективы Терапевтического Воздействия На Сигнальный Путь FGFR

“…Отмечены длительные периоды стабилизации при различных опу-холях -до 4-11 мес [43][44][45][46][47]. Интересные результаты были достигнуты и во II фазе исследования в комби-нации с химиотерапевтическими режимами при не-мелкоклеточном раке легкого и раке яичников [48,49]. В работах I / II фазы отмечена приемлемая переноси-мость и эффективность комбинации BIBF1120 с бева-цизумабом при раке толстой кишки.…”