<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_333"
                     title="More Benefits of Targeting HER2 in Breast Cancer (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/Oncology/BreastCancer/tb/18206?impressionId=1265804132198"
                     
      &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="-0.002"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18076?impressionId=1265804132198"
                     
      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="20100101_19_174"
                     title="AACR-IASLC: MicroRNA Linked to SCLC Response (CME/CE)"
                     score="-0.004"
                     href="http://www.medpagetoday.com/MeetingCoverage/AACR-IASLC/tb/18008?impressionId=1265804132198"
                     
      &lt;p&gt;CORONADO, Calif.  --  Tiny genetic segments may give a big tip-off to platinum chemoresistance in patients with small cell lung cancer, researchers said.&lt;/p&gt;
&lt;p&gt;Three microRNAs were linked to de novo chemoresistance in a small study led by Glen J. Weiss, MD, of Scottsdale Healthcare and the Translational Genomics Research Institute (TGen), both in Scottsdale, Ariz.&lt;/p&gt;
&lt;p&gt;He presented the results here at the Joint Conference on Molecular Origins of Lung Cancer sponsored by the American Association for Cancer Research and the International Association for the Study of Lung Cancer.&lt;/p&gt;
&lt;p&gt;Further validation would be needed before denying any patient chemotherapy based on the findings, cautioned Tyler Jacks, PhD, of the Massachusetts Institute of Technology and president of the AACR.&lt;/p&gt;
&lt;p&gt;However, &quot;biomarkers of this sort will be useful in diagnosing patients and applying relevant therapies  --  in this instance perhaps applying novel therapies, given the belief that the conventional therapies will be of no value to these individuals,&quot; he said as discussant on the study at a press conference.&lt;/p&gt;
&lt;p&gt;Weiss agreed.&lt;/p&gt;
&lt;p&gt;&quot;This is early stage,&quot; he said in an interview. &quot;But hopefully down the road it will have implications for treating patients with small cell [lung cancer].&quot;&lt;/p&gt;
&lt;p&gt;Non-small cell lung cancer has been a success story for personalized treatment.&lt;/p&gt;
&lt;p&gt;It was revolutionized by discovery of epidermal growth factor receptor (EGFR) mutations as both a prognostic factor and treatment target for the EGFR tyrosine kinase inhibitors.&lt;/p&gt;
&lt;p&gt;But for small cell lung cancer, the standard treatment is platinum-based chemotherapy with only two real options in first-line treatment, the researchers said.&lt;/p&gt;
&lt;p&gt;Worse, 15% to 30% of small cell tumors are intrinsically resistant to platinum chemotherapy and never respond.&lt;/p&gt;
&lt;p&gt;&quot;[Small cell] lung cancer patients haven&apos;t had a real advance in 15 years or more for chemotherapy,&quot; Weiss told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;What we&apos;re trying to do is identify the group that doesn&apos;t respond to standard therapy so that we can identify new treatments for them up front instead of treating everyone the same.&quot;&lt;/p&gt;
&lt;p&gt;Among the genetic possibilities for these efforts, microRNA  --  RNA molecules of around 20 nucleotides in length  --  are a good option, Weiss explained.&lt;/p&gt;
&lt;p&gt;They regulate gene expression like messenger RNA but are smaller and more stable across a variety of fluid and tissue types, he said.&lt;/p&gt;
&lt;p&gt;In the study, the researchers analyzed diagnostic tumor samples from 34 patients with small cell lung cancer.&lt;/p&gt;
&lt;p&gt;Among them, 19% had de novo chemoresistance marked by progressive disease. Most had had a partial or complete response to chemotherapy (61.9% and 9.5%, respectively).&lt;/p&gt;
&lt;p&gt;After extraction of total RNA, microRNA profiling revealed 16 top candidates for association with progressive disease.&lt;/p&gt;
&lt;p&gt;The 28 samples with sufficient RNA for further testing showed three microRNAs linked to chemoresistance that were validated by quantitative real-time PCR: &lt;ul&gt; &lt;li&gt;miR-92a-2* with a &lt;em&gt;P&lt;/em&gt;-value of 0.010&lt;/li&gt; &lt;li&gt;miR-147 with a &lt;em&gt;P&lt;/em&gt;-value of 0.018&lt;/li&gt; &lt;li&gt;miR-574-5p with a &lt;em&gt;P&lt;/em&gt;-value of 0.039&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Many of the patients had comorbidities at baseline, including 47.1% with hypertension and 32% with emphysema or chronic obstructive pulmonary disease. But these did not predict chemotherapy response.&lt;/p&gt;
&lt;p&gt;The next step is to validate the biomarkers in an independent cohort of small cell lung cancer patients, the researchers concluded.&lt;/p&gt;
&lt;p&gt;Then studies will need to determine what does work in these chemoresistant patients, Weiss said.&lt;/p&gt;
&lt;p&gt;&quot;We&apos;ve learned that if we&apos;re going to make the next hurdle and if we&apos;re going to better treat this disease, we need more personalized care,&quot; agreed Roy Herbst, MD, PhD, of M.D. Anderson Cancer Center in Houston.&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 the American Cancer Society-Sylvia Chase Pilot Grant, IBIS Foundation of Arizona, and the TGen Foundation.&lt;/p&gt;&lt;p&gt;Weiss reported recieving lab support from TGen Foundation and Scottsdale Healthcare Foundation as well as being party to provisional patents related to microRNAs in lung cancer.&lt;/p&gt;&lt;p&gt;Jacks provided no information on conflicts of interest.&lt;/p&gt;&lt;p&gt;Herbst has reported financial relationships with Genentech, Lilly, Amgen, and AstraZeneca. &lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_4069"
                     title="SABCS: Trastuzumab Dosing During Chemo Vindicated (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/SABCS/tb/17505?impressionId=1265804132198"
                     
      &lt;p&gt;SAN ANTONIO  --  Delaying trastuzumab (Herceptin) until chemotherapy is finished may impair outcomes for women with breast cancer, researchers found.&lt;/p&gt;
&lt;p&gt;Women with HER2-positive cancer had 25% better disease-free survival rates at five years when trastuzumab was started concurrently with chemotherapy, rather than sequentially (80.1% versus 84.2%, &lt;em&gt;P&lt;/em&gt;=0.019), Edith Perez, MD, of the Mayo Clinic in Jacksonville, Fla., and colleagues reported here at the San Antonio Breast Cancer Symposium.&lt;/p&gt;
&lt;p&gt;&quot;Based on a positive risk/benefit ratio, we recommend that adjuvant trastuzumab be incorporated in a concurrent fashion with the taxane portion of chemotherapy,&quot; Perez said.&lt;/p&gt;
&lt;p&gt;These findings largely confirm current U.S. practice, which is weighted toward concurrent scheduling.&lt;/p&gt;
&lt;p&gt;Both methods are sanctioned by the FDA in the United States, Perez said, but that that isn&apos;t generally the case elsewhere. In most countries, only the sequential strategy is approved.&lt;/p&gt;
&lt;p&gt;For that reason, many oncologists have eagerly awaited these findings, according to Claudine Isaacs, MD, of the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C., who moderated a press conference at which the results were presented.&lt;/p&gt;
&lt;p&gt;The study included 3,133 women with HER2-positive tumors randomized to anthracycline-based chemotherapy alone (doxorubicin [Adriamycin] and cyclophosphamide [Cytoxan] followed by paclitaxel [Taxotere]); to the same chemotherapy with trastuzumab started concurrently with the paclitaxel, or with trastuzumab started after all chemotherapy was done.&lt;/p&gt;
&lt;p&gt;Trastuzumab treatment continued for a total of 52 weeks in the two experimental arms.&lt;/p&gt;
&lt;p&gt;The trial was complicated by temporary closure of the concurrent trastuzumab arm early in the study for analysis of potential adverse cardiac events.&lt;/p&gt;
&lt;p&gt;As previously reported, the cardiac adverse event rate was 3.3% in the concurrent trastuzumab arm compared with 2.8% in the sequential arm and just 0.3% in the chemotherapy-only group.&lt;/p&gt;
&lt;p&gt;While much discussion has focused on this difference, most cases were manageable with appropriate medical therapy, Perez said.&lt;/p&gt;
&lt;p&gt;Results from another &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/SABCS/17497&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/SABCS/17497&quot; target=&quot;_blank&quot;&gt;large trial&lt;/a&gt; presented here at SABCS suggested that eliminating the anthracycline would reduce cardiac toxicity associated with trastuzumab therapy while preserving outcomes, but Perez cautioned that the risk of cancer recurrence is much more important to patients and oncologists than the potential for cardiac problems.&lt;/p&gt;
&lt;p&gt;&quot;At least we can manage it [cardiac toxicity] and the patient can survive,&quot; Perez told &lt;em&gt;MedPage Today&lt;/em&gt;. &quot;The biggest issue is recurrence.&quot;&lt;/p&gt;
&lt;p&gt;Both trastuzumab strategies appeared more effective at five years for the primary endpoint of disease-free survival, compared with the chemotherapy-only control group.&lt;/p&gt;
&lt;p&gt;Midway through the trial, all control patients were allowed to crossover to receive trastuzumab while those on sequential trastuzumab could crossover to concurrent dosing.&lt;/p&gt;
&lt;p&gt;With crossovers censored, sequential therapy yielded a 33% higher disease-free survival rate (80.1% versus 71.9%, &lt;em&gt;P&lt;/em&gt;=0.0005). For the concurrent strategy, the difference was significant as well (HR 0.48, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.00001).&lt;/p&gt;
&lt;p&gt;Although the concurrent trastuzumab strategy appeared significantly better than sequential administration, Perez&apos;s group said they could only call it a strong trend.&lt;/p&gt;
&lt;p&gt;&quot;This is based on the fact that the results of this long-term follow-up are based on a first interim analysis [for this comparison],&quot; she said.&lt;/p&gt;
&lt;p&gt;Projections made during the trial design &quot;were completely off,&quot; with twice as many disease-free survival events projected to be required for statistical power, Perez explained.&lt;/p&gt;
&lt;p&gt;So at a little over five years into the trial, the first interim analysis was triggered at 312 total events (50% of planned) for comparison between trastuzumab schedule arms, she said. The P-value needed for statistical significant in the comparison would have been at 0.0001, she said.&lt;/p&gt;
&lt;p&gt;The effectiveness of concurrent therapy was supported by the overall survival analysis, which showed a significant benefit compared with the chemotherapy-only arm (HR 0.65, &lt;em&gt;P&lt;/em&gt;=0.0007). whereas the sequential arm did not differ from either other arm (&lt;em&gt;P&lt;/em&gt;=0.281 and &lt;em&gt;P&lt;/em&gt;=0.135).&lt;/p&gt;
&lt;p&gt;Perez attributed the benefit of concurrent scheduling to synergy between the taxane and trastuzumab.&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 funded by the National Cancer Institute, Genetech, and the Breast Cancer Research Foundation.&lt;/p&gt;&lt;p&gt;Perez reported serving on the steering committee for sorafenib (Nexavar) and for a Genetech trial and serving on an independent monitoring committe for Novartis, all without direct funding from the companies.&lt;/p&gt;&lt;p&gt;Isaacs reported serving on the speakers bureau for GlaxoSmithKline, Genentech, Novartis, and AstraZeneca.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_355"
                     title="SABCS: Dose-Dense Chemotherapy Called Safe and Effective"
                     score="-0.005"
                     href="