PURPOSE NALA (ClinicalTrials.gov identifier: NCT01808573 ) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens. METHODS Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m2 twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m2 twice a day 14 d/21 d). Coprimary end points were centrally confirmed progression-free survival (PFS) and overall survival (OS). NALA was considered positive if either primary end point was met (α split between end points). Secondary end points were time to CNS disease intervention, investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate, safety, and health-related quality of life (HRQoL). RESULTS A total of 621 patients from 28 countries were randomly assigned (N+C, n = 307; L+C, n = 314). Centrally reviewed PFS was improved with N+C (hazard ratio [HR], 0.76; 95% CI, 0.63 to 0.93; stratified log-rank P = .0059). The OS HR was 0.88 (95% CI, 0.72 to 1.07; P = .2098). Fewer interventions for CNS disease occurred with N+C versus L+C (cumulative incidence, 22.8% v 29.2%; P = .043). ORRs were N+C 32.8% (95% CI, 27.1 to 38.9) and L+C 26.7% (95% CI, 21.5 to 32.4; P = .1201); median DoR was 8.5 versus 5.6 months, respectively (HR, 0.50; 95% CI, 0.33 to 0.74; P = .004). The most common all-grade adverse events were diarrhea (N+C 83% v L+C 66%) and nausea (53% v 42%). Discontinuation rates and HRQoL were similar between groups. CONCLUSION N+C significantly improved PFS and time to intervention for CNS disease versus L+C. No new N+C safety signals were observed.

Background Knowledge of independent, baseline risk factors of catheter-related thrombosis (CRT) may help select adult cancer patients at high risk to receive thromboprophylaxis. Objectives We conducted a meta-analysis of individual patient-level data to identify these baseline risk factors. Patients/Methods MEDLINE, EMBASE, CINAHL, CENTRAL, DARE, Grey literature databases were searched in all languages from 1995-2008. Prospective studies and randomized controlled trials (RCTs) were eligible. Studies were included if original patient-level data were provided by the investigators and if CRT was objectively confirmed with valid imaging. Multivariate logistic regression analysis of 17 prespecified baseline characteristics was conducted. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Results A total sample of 5636 subjects from 5 RCTs and 7 prospective studies was included in the analysis. Among these subjects, 425 CRT events were observed. In multivariate logistic regression, the use of implanted ports as compared with peripherally implanted central venous catheters (PICC), decreased CRT risk (OR = 0.43; 95% CI, 0.23-0.80), whereas past history of deep vein thrombosis (DVT) (OR = 2.03; 95% CI, 1.05-3.92), subclavian venipuncture insertion technique (OR = 2.16; 95% CI, 1.07-4.34), and improper catheter tip location (OR = 1.92; 95% CI, 1.22-3.02), increased CRT risk. Conclusions CRT risk is increased with using PICC catheters, previous history of DVT, subclavian venipuncture insertion technique and improper positioning of the catheter tip. These factors may be useful for risk stratifying patients to select those for thromboprophylaxis. Prospective studies are needed to validate these findings.

The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.

To see whether D-Dimer levels can identifying patients at high risk of venous thrombotic events and establish the best benefit/risk-of-bleeding ratio. Current guidelines do not recommend routine prophylaxis against venous thromboembolism (VTE) in cancer patients receiving chemotherapy, but the risk increases about 6.5-fold because of this treatment. D-dimer was measured at baseline in 124 cancer patients scheduled for their first chemotherapy. VTE events, including symptomatic episodes of deep vein thrombosis or pulmonary embolism or both, were recorded during the first 6 months of therapy, and asymptomatic deep vein thrombosis was revealed by compression ultrasonography at baseline and after 90 and 180 days. During follow-up, there were 11 episodes of VTE (8.9%). Mean D-dimer values were higher in patients with VTE (2195 +/- 1382 vs. 695 +/- 1039 ng/ml, (P < 0.001). On grouping D-dimer values in tertiles, only 2.4% (confidence interval, 0.9-5.7%) in the first (<262 ng/ml) and second tertiles (262-650 ng/ml) suffered a deep vein thrombosis/pulmonary embolism event as compared with 22% (confidence interval, 9-34%) in the third (>650 ng/dl) (P = 0.003). The VTE-free interval was significantly shorter in the third tertile than in the first (P = 0.0218, log-rank test; relative risk for third vs. first tertile, 11.0; 95% confidence interval, 1.4-81.3; P = 0.0033). Multivariate analysis found that only baseline D-dimer concentrations were correlated with the subsequent development of VTE. Baseline D-dimer values in cancer patients scheduled for chemotherapy might be used to select those at low risk of VTE, most likely to be safe without prophylaxis.

Background: Recent guidelines do not recommend antithrombotic prophylaxis (AP) to prevent catheter-related thrombosis in cancer patients with a central line. Patients and methods:This study assessed the management of central lines in cancer patients, current attitude towards AP, catheter-related and systemic venous thromboses, and survival.Results: Of 1410 patients enrolled, 1390 were seen at least once in the 6-month median follow-up. Continuous AP, mainly low-dose warfarin, was given to 451 (32.4%); they were older, with a more frequent history of venous thromboembolism (VTE), and more advanced cancer. There was no difference in catheter-related thrombosis in patients given AP or not (2.8% and 2.2%, odds ratio 1.29, 95% confidence interval 0.64-2.6). The median time to first catheter-related complication was 120 days. Systemic VTE including deep and superficial thromboses and pulmonary embolism, were less frequent with AP (4% versus 8.2%, P = 0.005). Mortality was also lower (25% versus 44%, P = 0.0001). Multiple logistic regression analysis found only advanced cancer and no AP significantly associated with mortality. No major bleeding was recorded with AP.Conclusions: Current AP schedules do not appear to prevent catheter-related thrombosis. Systemic VTE and mortality, however, appeared lower after prophylaxis.