Second-Line Treatment of Her2-Positive Metastatic Breast Cancer: Trastuzumab beyond Progression or Lapatinib? A Population Based Cohort Study.

The relative efficacy of lapatinib vs. continuing trastuzumab beyond progression (TBP) in HER2-positive metastatic breast cancer (MBC) patients, who progressed on first-line trastuzumab, is still unclear. The objective of this population based cohort study was to compare outcomes of lapatinib vs. TBP in daily practice.All HER2-positive MBC patients who began second-line anti HER2 therapy between 1st January 2010 and 30th August 2013 were selected from Clalit Health Services' (CHS) electronic database. Available data on patient and disease characteristics and treatments were analyzed. The primary endpoint was overall survival (OS). Outcomes were compared using the Kaplan-Meier (log-rank) method and Cox proportional hazards model.64 patients received second-line lapatinib and 93 TBP. The two treatment groups were similar in age and co-morbidity rates, but differed in proportion of prior adjuvant trastuzumab (lapatinib: 29.7%, TBP: 16.1%, P = 0.043) and rates of prior brain metastases (lapatinib: 32.8%, TBP: 10.8%, P = 0.01). Lapatinib median OS was 13.0 months (95% CI: 9.5-16.5) vs. 31.0 for TBP (95% CI: 20.6-41.4), P<0.001. On multivariate analysis, longer OS was preserved for TBP, after controlling for differences in age, adjuvant trastuzumab, duration of first-line trastuzumab therapy, brain metastases, visceral metastases and hormonal treatment [Hazard Ratio (HR) = 0.63, 95% CI: 0.40-0.99, P = 0.045].In this comparative cohort study, OS of HER2-positive MBC patients treated with TBP was significantly longer than with lapatinib. These results might be especially relevant in settings where ado-trastuzumab-emtansine (TDM-1), the current preferred agent in this setting, is not available yet for patients

Unadjusted and Adjusted Cox's proportional Hazards Models^*.

*<p>All models were adjusted for age, gender, eGFR, hemoglobin, previous infarction, hypertension, diabetes mellitus, smoking, baseline hemoglobin, serum calcium, ST-elevation infarction, Killip class, coronary revascularization, LVEF.</p>†<p>Heart failure, myocardial infarction or stroke.</p

Kaplan-Meier survival plot of mortality.

<p>Patients are divided by categories of serum phosphorus. <i>P</i> values are for the overall comparison among the groups using the log rank test.</p

Cubic spline analysis.

<p>The plot describes the relationship between serum phosphorus as a continuous variable and the probability of mortality. The blue area indicates the 95% confidence interval.</p

Relationship between serum phosphorus and renal function. A.

<p>Box–and–whisker plots of changes in serum phosphorus level according to the severity of renal dysfunction. The line within the box denotes the median and the box spans the interquartile range (25th to 75th percentiles). Whiskers extend from the 5th to 95th percentiles. <b>B.</b> Spline function graph of the relationship between estimated glomerular filtration rate and serum phosphorus, showing the shape of the relationship curve on a continuous basis. The blue area with dotted lines indicate the 95% confidence interval.</p

Pulmonary arterial capacitance in patients with heart failure and reactive pulmonary hypertension

Abstract AIMS: Reactive pulmonary hypertension (PH) is a severe form of PH secondary to left-sided heart failure (HF). Given the structural and functional abnormalities in the pulmonary vasculature that occur in reactive PH, we hypothesized that pulmonary artery capacitance (PAC) may be profoundly affected, with implications for clinical outcome. METHODS AND RESULTS: We studied 393 HF patients of whom 124 (32%) were classified as having passive PH and 140 (36%) as having reactive PH, and 91 patients with pulmonary arterial hypertension (PAH). Mean PAC was highest in patients without PH (4.5\u2009\ub1\u20092.1\u2009mL/mmHg), followed by the passive PH group (2.8\u2009\ub1\u20091.4\u2009mL/mmHg) and was lowest in those with reactive PH (1.8\u2009\ub1\u20090.7\u2009mL/mmHg) (P\u2009=\u20090.0001). PAC and pulmonary vascular resistance (PVR) fitted well to a hyperbolic inverse relationship (PAC\u2009=\u20090.25/PVR, R(2) \u2009=\u20090.70), with reactive PH patients dispersed almost predominantly on the flat part of the curve where a reduction in PVR is associated with a small improvement in PAC. Elevated PCWP was associated with a significant lowering of PAC for any PVR (P\u2009=\u20090.036). During a median follow-up of 31 months, both reactive PH [hazard ratio (HR) 2.59, 95% confidence interval (CI) 1.14-4.46, P\u2009=\u20090.02] and reduced PAC (HR 0.72 per 1\u2009mL/mmHg increase, 95% CI 0.59-0.88, P\u2009=\u20090.001) were independent predictors of mortality. CONCLUSIONS: The development of reactive PH is associated with a marked reduction in PAC. PAC is a strong independent haemodynamic marker of mortality in HF and may contribute to the increased mortality associated with reactive PH

Combined effect of serum phosphorus and CKD.

<p>The figure shows adjusted hazard ratios and 95% confidence intervals for mortality according to serum phosphorus categories and CKD. The reference group includes patients with serum phosphorus of 2.50 to 3.50 mg/dL and without CKD. The number of patients in each group is shown above each bar.</p