Mary Ann Allison

PURPOSE: The activity and safety of eribulin mesylate (E7389), a nontaxane microtubule dynamics inhibitor with a novel mechanism of action, were evaluated in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline, taxane, and capecitabine. PATIENTS AND METHODS: Eligible patients in this single-arm, open-label phase II study received eribulin mesylate (1.4 mg/m(2)) administered as a 2- to 5-minute intravenous infusion on days 1 and 8 of a 21-day cycle. The primary end point was objective response rate (ORR) assessed by independent review. RESULTS: Of 299 enrolled patients who had received a median of four prior chemotherapy regimens, 291 received eribulin (for a median of four cycles). Of these, 269 patients met key inclusion criteria for the primary efficacy analysis. The primary end point of ORR by independent review was 9.3% (95% CI, 6.1% to 13.4%; all partial responses [PRs]), the stable disease (SD) rate was 46.5%, and clinical benefit rate (complete response + PR + SD > or = 6 months) was 17.1%. The investigator-reported ORR was 14.1% (95% CI, 10.2% to 18.9%). Median duration of response was 4.1 months, and progression-free survival was 2.6 months. Median overall survival was 10.4 months. The most common treatment-related grade 3 or 4 toxicities were neutropenia (54%; febrile neutropenia, 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4); grade 3 neuropathy occurred in 6.9% of patients (no grade 4). CONCLUSION: Eribulin demonstrated antitumor activity in extensively pretreated patients who had previously received an anthracycline, taxane, and capecitabine, with a manageable tolerability profile.

This text provides examples from multinational businesses to show readers concrete and practical methods, based on complexity theory, for solving practical business problems. The book also seeks to demonstrate how discoveries from the new sciences can help businesses and organizations get out of destructive practices, and embrace constructive ones. Traditional business management models have proved unsuccessful, according to the authors, including the well-mentioned quality and empowerment programmes. The book argues that in a world growing more complex, understanding complexity theory can make the difference. The text recommends specific business evolution methods and principles which use concepts from the new sciences to make business more effective and profitable. Recommendations include: understanding key concepts from the new sciences and from higher mathematics; developing a practical working knowledge of people and businesses as complex adaptive systems; engaging a few simple rules, simple and elegant, but not simple-minded; and adopting their 14 principles of business evolution, founded on an understanding of self-organizing systems and concepts from the new sciences.

BACKGROUND: In this study, the authors evaluated whether a pathologic complete response (pCR) or a clinical complete response (cCR) to neoadjuvant treatment in patients with locally advanced breast cancer differed among the 3 subtypes of breast cancer: triple-negative breast cancer (TNBC), human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and hormone receptor-positive/HER2-negative breast cancer. Whether a cCR or a pCR was correlated with fewer recurrences and better survival also was investigated. METHODS: Patients with stage II/III breast cancer received 4 cycles of neoadjuvant docetaxel and carboplatin (TC) every 3 weeks. Patients with HER2-positive tumors were randomized to receive either additional weekly trastuzumab preoperatively or TC alone. Postoperatively, all patients received 4 cycles of TC, and all HER2-positive patients received a total of 52 weeks of trastuzumab. The recurrence-free survival (RFS) and overall survival (OS) rates at 2 years were reported. RESULTS: Seventy-four patients were enrolled, including 11 patients with TNBC, 30 patients with HER2-positive tumors, and 33 patients with hormone receptor-positive/HER2-negative tumor. The cCR rates were 45.4%, 50% and 40.6% in TNBC, HER2-positive, and hormone receptor-positive/HER2-negative groups, respectively. The pCR rate for the entire group was 26.8%, and patients with TNBC had the best response (54.6%) followed by patients with HER2-positive tumors (24.1%) and patients with hormone receptor-positive/HER2-negative tumors (19.4%; P = .0126). The pCR rate for patients with HER2-positive tumors improved from 7% to 40% if trastuzumab was added (P = .08). Infiltrating ductal cancer, TNBC, negative estrogen receptor and/or progesterone receptor status, tumor classification predicted a pCR (P ≤ .05). Multivariate analysis using a logistic regression test indicated that tumor type was an independent predictor. The RFS rate for patients who did versus patients who did not achieve a pCR was 93.8% versus 78.4% at 2 years, respectively, and 83.3% versus 58% at 3 years, respectively (P = .1227); whereas, for patients who did versus patients who did not achieve a cCR, the RFS rate was 80.9% versus 83.9%, respectively, at 2 years and 65% versus 64.3%, respectively, at 3 years (P = .999). CONCLUSIONS: The current results indicated that the TC combination is promising for the treatment of TNBC. The addition of trastuzumab to TC improved the pCR rate significantly in patients with HER2-positive breast cancer.