A phase II study of afatinib (BIBW 2992), an irreversible ErbB family blocker, in patients with HER2-positive metastatic breast cancer progressing after trastuzumab

Afatinib is an oral, ErbB family blocker, which covalently binds and irreversibly blocks all kinase-competent ErbB family members. This phase II, open-label, single-arm study explored afatinib activity in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients progressing after trastuzumab treatment. Patients had stage IIIB/IV HER2-positive metastatic breast cancer, with progression following trastuzumab or trastuzumab intolerance and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. Patients received 50mg afatinib once-daily until disease progression. Primary endpoint was objective response rate (Response Evaluation Criteria in Solid Tumors 1.0), with tumor assessments every 8weeks. Forty-one patients were treated. Patients had received a median of three prior chemotherapy lines (range, 0–15) and 68.3% had received trastuzumab for >1year. Four patients (10% of 41 treated; 11% of evaluable patients) had partial response. Fifteen patients (37% of 41) had stable disease as best response and 19 (46% of 41) achieved clinical benefit. Median progression-free survival was 15.1weeks (95% confidence interval [CI]: 8.1–16.7); median overall survival was 61.0weeks (95% CI: 56.7–not evaluable). Most frequent common terminology criteria for adverse events grade 3 treatment-related adverse events were diarrhea (24.4%) and rash (9.8%). Afatinib monotherapy was associated with promising clinical activity in extensively pretreated HER2-positive breast cancer patients who had progressed following trastuzumab treatment.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-012-2003-y) contains supplementary material, which is available to authorized users

Plant mobility in the Mesozoic: Disseminule dispersal strategies of Chineseand Australian Middle Jurassic to Early Cretaceous plants

Four upper Middle Jurassic to Lower Cretaceous lacustrine Lagerstätten in China and Australia (the Daohugou, Talbragar, Jehol, and Koonwarra biotas) offer glimpses into the representation of plant disseminule strategies during that phase of Earth history in which flowering plants, birds, mammals, and modern insect faunas began to diversify. No seed or foliage species is shared between the Northern and Southern Hemisphere fossil sites and only a few species are shared between the Jurassic and Cretaceous assemblages in the respective regions. Freesporing plants, including a broad range of bryophytes, are major components of the studied assemblages and attest to similar moist growth habitats adjacent to all four preservational sites. Both simple unadorned seeds and winged seeds constitute significant proportions of the disseminule diversity in each assemblage. Anemochory, evidenced by the development of seed wings or a pappus, remained a key seed dispersal strategy through the studied interval. Despite the rise of feathered birds and fur-covered mammals, evidence for epizoochory is minimal in the studied assemblages. Those Early Cretaceous seeds or detached reproductive structures bearing spines were probably adapted for anchoring to aquatic debris or to soft lacustrine substrates. Several relatively featureless seeds in all assemblages were potentially adapted to barochory or to endozoochory—the latter evidenced especially by the presence of smooth seeds in vertebrate gut contents and regurgitant or coprolitic masses. Hydrochory is inferred for several aquatic plants that notably bear small featureless seeds, particularly aggregated into detachable pods.Funding also from the National Science Foundation project #1636625</p