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    <recommendedItem id="20100101_19_333"
                     title="More Benefits of Targeting HER2 in Breast Cancer (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/Oncology/BreastCancer/tb/18206?impressionId=1265784604811"
                     
      &lt;p&gt;The addition of trastuzumab (Herceptin) before and after surgery significantly improved event-free survival compared with neoadjuvant chemotherapy alone in women with HER2-positive locally advanced or inflammatory breast cancer, investigators in a multicenter European trial reported.&lt;/p&gt;
&lt;p&gt;Patients treated with trastuzumab had a 40% reduction in the hazard ratio for the composite endpoint of recurrence, progression, or death from any cause.&lt;/p&gt;
&lt;p&gt;&quot;Although locally advanced breast cancer is relatively infrequent in affluent countries compared with nonaffluent countries, it is still an area of medical need, especially in regions of the world where diagnosis tends to occur late for cultural or economic reasons,&quot; Luca Gianni, MD, of the National Cancer Institute in Milan, Italy, and colleagues wrote in the Jan. 30 issue of &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Neoadjuvant chemotherapy has a key role in the management of patients with locally advanced and inflammatory cancers. Anthracycline- and taxane-based regimens have produced high response rates and rates of breast-conserving surgery for patients with operable breast cancer, the authors wrote.&lt;/p&gt;
&lt;p&gt;About 35% of locally advanced and 40% of inflammatory breast cancers are associated with HER2 amplification or overexpression. Trastuzumab, which targets HER2, has demonstrated efficacy as monotherapy and in combination with chemotherapy for patients with HER2-positive metastatic and early operable breast cancer, the authors continued.&lt;/p&gt;
&lt;p&gt;Trastuzumab does not have specific approval for treatment of locally advanced or inflammatory breast cancer and has not been studied extensively for those indications. So the investigators designed the neoadjuvant Herceptin (NOAH) study to assess the efficacy of neoadjuvant chemotherapy plus trastuzumab followed by adjuvant trastuzumab.&lt;/p&gt;
&lt;p&gt;The randomized trial compared the regimen versus neoadjuvant chemotherapy alone in 235 patients with newly diagnosed HER2-positive locally advanced or inflammatory breast cancer.&lt;/p&gt;
&lt;p&gt;The investigators conducted a parallel observational study involving 99 patients with newly diagnosed HER2-negative locally advanced or inflammatory breast cancer. Those patients too were treated with chemotherapy alone, which consisted of doxorubicin, paclitaxel, cyclophosphamide, methotrexate, and 5-FU.&lt;/p&gt;
&lt;p&gt;The primary endpoint was event-free survival, defined as the time from randomization to disease recurrence or progression or death from any cause.&lt;/p&gt;
&lt;p&gt;After a median follow-up of 3.2 years, the three-year event-free survival was 71% in the trastuzumab arm and 56% in the patients who received chemotherapy without trastuzumab. The difference translated into an unadjusted hazard ratio of 0.59 (95% CI 0.38 to 0.90, &lt;em&gt;P&lt;/em&gt;=0.013).&lt;/p&gt;
&lt;p&gt;Regression analysis confirmed that treatment with trastuzumab was the only factor that significantly affected event-free survival, resulting in a hazard ratio of 0.58 compared with the chemotherapy-only arm (&lt;em&gt;P&lt;/em&gt;=0.126).&lt;/p&gt;
&lt;p&gt;Three-year overall survival was not significantly different between the treatment arms of HER2-positive patients but trended in favor of the trastuzumab arm (87% versus 79%). The authors noted that the 17% crossover to treatment with trastuzumab may have lessened the observed survival difference.&lt;/p&gt;
&lt;p&gt;The HER2-negative patients had a three-year event-free survival of 67% and overall survival of 86%.&lt;/p&gt;
&lt;p&gt;Rates and severity of noncardiac adverse events were similar in all three treatment groups, the authors reported. Fewer patients in the trastuzumab arm maintained normal left ventricular ejection fraction (LVEF) throughout the study, but most reductions in LVEF were grade 1 in severity. Two patients had grade 2 (asymptomatic) reductions in LVEF, and two had reversible grade 3 decreases.&lt;/p&gt;
&lt;p&gt;Gianni and colleagues acknowledged that the benefit in the trastuzumab arm could have occurred as a result of both neoadjuvant and adjuvant use of trastuzumab. However, the magnitude of the benefit (HR 0.59) was greater and the number needed to treat was lower compared with adjuvant trials of trastuzumab, Melanie D. Seal, MD, and Stephen K. Chia, MD, of the British Columbia Cancer Agency in Vancouver, wrote in a commentary.&lt;/p&gt;
&lt;p&gt;&quot;Adjuvant studies require thousands of women to show survival benefits, at high cost and often long follow-up,&quot; Seal and Chia wrote. &quot;Studies such as NOAH illustrate the benefits and potential of neoadjuvant trials and should challenge the dogma of our current strategies of therapeutic trials in early-stage breast cancer.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by F. Hoffmann-La Roche.&lt;/p&gt;&lt;p&gt;Gianni disclosed relationships with Roche, Genentech, GlaxoSmithKline, Wyeth, Novartis, Millennium, Biogen Idec, and Eisai. Co-author Jose Baselga disclosed relationships with Exelixis, Merck, Novartis, Roche, and GlaxoSmithKline. Co-author Andrea Feyereislova is a Roche employee. Co-author Claire Barton disclosed relationships with Roche, ONO Pharma, Cellact, Acadia, Michelangelo, BTG Ltd, Kuros Biosurgery, Micromet AG, Bioenvision, Norgine, Piramed, and GlaxoSmithKline.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_223"
                     title="ASCO GI: Regimen Benefits Colon Cancer Patients of All Ages"
                     score="-0.004"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18076?impressionId=1265784604811"
                     
      ORLANDO -- Patients with early-stage colorectal cancer benefit from adjuvant chemotherapy with capecitabine (Xeloda) and oxaliplatin (Eloxatin) regardless of age, according to a new analysis of data from a large multicenter clinical trial.&lt;br&gt;
&lt;br&gt;Disease-free survival (DFS) at three years increased from 60% with a control regimen to 66% with the capecitabine/oxaliplatin (XELOX) regimen among patients 70 or older.&lt;br&gt;
&lt;br&gt;Younger patients had a 3% absolute improvement in three-year DFS when treated with the regimen (72% versus 69% for the control group).&lt;br&gt;
&lt;br&gt;Similar results emerged from an analysis that used 65 as the age cutpoint, according to a presentation at a press briefing prior to the 2010 Gastrointestinal Cancers Symposium.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;XELOX is a new standard of care for patients with early colon cancer, regardless of age,&quot; said Daniel G. Haller, MD, of the University of Pennsylvania. &quot;Patients receiving XELOX immediately after surgery live disease-free for longer, and there is a trend towards superior overall survival with XELOX.&quot;&lt;/p&gt;
&lt;p&gt;The results contradict those of other recent studies that showed no survival benefit with the XELOX regimen in older patients. The reasons for the contradictory findings have yet to be determined, said Haller.&lt;/p&gt;
&lt;p&gt;The findings came from a subgroup analysis of the NO16968 trial. It compared XELOX with bolus intravenous 5-FU/leucovorin, which was the standard of care for stage III colon cancer when the trial began.&lt;/p&gt;
&lt;p&gt;The analysis was performed after two studies reported last year showed that the survival benefit of the regimen was limited to younger patients (&lt;em&gt;ASCO&lt;/em&gt; 2009. Abstract 4010, &lt;em&gt;J Clin Oncol&lt;/em&gt; 2009; 27: 3109-116).&lt;/p&gt;
&lt;p&gt;NO16968 involved a total 1,886 patients, including 409 patients who were ages 70 or older. Study participants were randomized to XELOX or the control regimen, and the primary endpoint was DFS.&lt;/p&gt;
&lt;p&gt;After a median follow-up of 57 months, the three-year DFS in patients younger than 70 was 72% with XELOX and 69% with the control regimen, representing a 21% reduction in the hazard ratio (95% CI 0.66 to 0.94).&lt;/p&gt;
&lt;p&gt;Among older patients, the 6% absolute difference in DFS favoring XELOX constituted a 13% reduction in the hazard ratio (95% CI 0.63 to 1.18).&lt;/p&gt;
&lt;p&gt;When the definition of &quot;older&quot; patients was 65 and older, XELOX still resulted in a 6% absolute difference in DFS compared with the control regimen (68% versus 62%, HR 0.81, 95% CI 0.64 to 1.03). Among patients younger than 65, XELOX led to a three-year DFS of 72% versus 69% with 5FU and leucovorin (HR 0.80, 95% CI 0.65 to 0.98).&lt;/p&gt;
&lt;p&gt;In response to a question, Haller acknowledged that the DFS difference in older patients did not achieve statistical significance, but he said the principal objective of the study was to examine the data for evidence of trends.&lt;/p&gt;
&lt;p&gt;Overall survival data were not sufficiently mature to perform definitive analyses. However, Haller said the data demonstrated trends in favor of XELOX for all age groups evaluated.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Haller disclosed relationships with sanofi-aventis and Hoffmann-La Roche.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_3_125"
                     title="SABCS: Moderate Breast Cancer Therapy Benefits Total Big Mortality Drop"
                     score="-0.005"
                     href="