Arm 1, paclitaxel 100 mg/m2 weekly for 3 of 4 weeks with carboplatin (AUC = 6) administered on day 1, demonstrates the most favorable therapeutic index in patients with advanced NSCLC.

Background: Overexpression of HER2/neu is associated with upregulation of VEGF in human breast cancer cells in vitro. In xenograft models, superior efficacy is observed when anti-HER2 antibody trastuzumab (T) is given in combination with anti-VEGF antibody bevacizumab (B). Results from a phase I study of T + B (Breast Cancer Res Treat. 88:S124, 2004) were sufficiently positive to proceed with phase II testing. The objectives of this phase II study were to more fully determine clinical efficacy and safety of T + B.Methods: Women with normal cardiac function and bidimensionally measurable, HER2-amplified (FISH), metastatic or locally recurrent unresectable breast cancer were eligible. Patients (pts) were excluded if they had received chemotherapy in the metastatic setting, had CNS metastases, proteinuria, >3 different organ sites of metastasis, >50% parenchymal liver metastasis, or symptomatic lung metastases. Prior adjuvant T was allowed if it was discontinued ≥ 1 year before study entry. B (10mg/kg q 2 weeks) + T (4mg/kg loading, then 2mg/kg weekly) IV was given, per the results of phase I testing (above).Results: From 12/2004 to 4/2007, 50 pts were enrolled at 19 US sites. Pt characteristics: median age 58, prior breast surgery-38 (76%), prior radiation-22 (44%), prior (neo)adjuvant chemotherapy-26 (52%), prior anthracyclines-25 (50%), prior taxanes-20 (40%), prior endocrine therapy–23 (46%), visceral metastasis-36 (72%). A median of 6.25 cycles (range 1-34) were administered to pts. Drug-related adverse events (AEs) (all Grade (Gr) 3/4 and any events reported in >10% of patients, NCI-CTC v.2) included hypertension (N= 30: 18 Gr 3/4, 12 Gr 1/2), fever/chills/infusion reaction (N=18: 2 Gr 3/4, 16 Gr 1/2), headache (N=17: 2 Gr 3/4, 15 Gr 1/2), epistaxis (N=17: all Gr 1/2), fatigue (N=15: 1 Gr 3, 14 Gr 1/2), proteinuria (N=12: 4 Gr 3/4, 8 Gr 1/2), AST /ALT increase (N=12, all Gr 1/2), diarrhea (N=10: 1 Gr 3, 9 Gr 1/2), edema (N=6, all Gr 1/2), nail changes (N=6, all Gr 1/2), dyspnea (N=5: 2 Gr 3/4, 3 Gr 1/2), leucopenia (N=5: Gr 3/4=2, Gr 1/2=3), inflammatory demyelination (N=1, Gr 3), hyperglycemia (N=1, Gr 3), hyponatremia (N=1, Gr 3) and irregular menses (N=1, Gr 3). One pt developed a perforated ulcer and 4 weeks later died of sepsis (Gr 5). One Gr 4 cardiac AE was reported at the end of cycle 2 in a pt who had previously received doxorubicin. In addition, there were 9 Gr 2 and 9 Gr 1 cardiac AEs (all asymptomatic). Objective clinical responses (WHO criteria) were documented in 24 pts (48%), including 2 CRs. 15 pts (30%) had stable disease, 6 of which lasted ≥ 6 mos (12%) for a clinical benefit rate of 60%. No pts remain on active study treatment. The median time to progression (TTP) was 9.2 mos (95% CI: 5.4-20.5). No difference in TTP was detected between hormone receptor negative and positive tumor types. Median overall survival was 43.8 months (95% CI: 40.6,NA).Conclusions: These are the final results for the first phase II trial of 2 humanized antibodies given in combination to human subjects. The results show that T + B is clinically feasible and very active despite the absence of chemotherapy in HER2+ advanced breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6094.

BACKGROUNDFine‐needle aspiration biopsy (FNAB) is a reliable, rapid, minimally invasive alternative to surgical biopsy when it is performed by physician specialists for the diagnosis of palpable masses. FNAB may be under‐utilized in community hospitals in the U.S. because physicians without specialty training commonly provide the service, resulting in less reliable results.METHODSRecords were reviewed retrospectively from 730 consecutive FNAB cases that were performed and interpreted by expert cytopathologists practicing in an outpatient community hospital setting between 2000 and 2004. Data concerning patient demographics, referring physician specialty type, body sites, diagnoses, specimen adequacy, accuracy of diagnosis, and follow‐up were examined and analyzed.RESULTSFNAB was diagnostic in 93% of patients and was 95% accurate. There were 5 false‐negative results and no false‐positive results for the diagnosis of malignancy. The overall sensitivity of FNAB was 93%, and the specificity was 100%. Using either histology or clinical follow‐up, the positive predictive value was 100%, and the negative predictive value was 99%.CONCLUSIONSHighly reliable results can be obtained when patients are referred to specialty‐trained cytopathologists practicing in the community for FNAB of palpable mass lesions. Clinicians are encouraged to seek out and support specialized FNAB services in their own communities. Cancer 2006. © 2006 American Cancer Society.