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<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3184"
                     title="Anti-HER2 Drug Fails to Win FDA Fast Track"
                     score="0.013"
                     href="http://www.medpagetoday.com/PublicHealthPolicy/FDAGeneral/tb/21915?impressionId=1283456783629"
                     
      &lt;p&gt;WASHINGTON  --  The Food and Drug Administration turned down a request for accelerated approval of Roche-Genentech&apos;s trastuzumab-DM1 drug for the treatment of HER2-positive breast cancer.&lt;/p&gt;
&lt;p&gt;The FDA concluded that the supporting data for trastuzumab-DM1 did not meet the Biologic License Application (BLA) Standard for accelerated approval because all available treatment choices for metastatic breast cancer  --  irrespective of HER2 status  --  had not been exhausted.&lt;/p&gt;
&lt;p&gt;Roche had requested accelerated approval on the basis of a single-arm phase II study showing that trastuzumab-DM1 led to tumor responses in a third of patients with advanced HER2-positive breast cancer. Patients in the trial had received an average of seven prior regimens.&lt;/p&gt;
&lt;p&gt;An ongoing phase III study will continue as planned. In a statement from the company, Roche officials said they expect a global regulatory submission for trastuzumab-DM1 by the middle of 2012.&lt;/p&gt;
&lt;p&gt;Trastuzumab-DM1 is an antibody-drug conjugate, also known as an armed antibody. Conjugate links trastuzumab with the chemotherapy agent DM1, using a stable linker that keeps the agent in one piece until it reaches its target cancer cells, according to a Roche statement. The antibody is designed to bind and penetrate HER2-positive cancer cells and then release the active drug inside the cells to destroy them.&lt;/p&gt;
&lt;p&gt;Roche is headquartered in Basel, Switzerland. Genentech, based in San Francisco, Calif., is a unit of Roche.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_3124"
                     title="Myeloma Responds to Less-Intense Therapy (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/HematologyOncology/Myeloma/tb/21839?impressionId=1283456783629"
                     
      &lt;p&gt;Older patients with newly diagnosed myeloma had no loss of efficacy and significantly less toxicity with reduced-intensity induction therapy followed by maintenance, results of a multicenter Spanish study showed.&lt;/p&gt;
&lt;p&gt;Two regimens based on less frequent dosing of bortezomib (Velcade) led to major responses in 80% of patients during induction therapy and to complete response rates of about 40% after maintenance therapy, Maria-Victoria Mateos, MD, of University Hospital of Salamanca, and co-authors concluded in an article reported online in &lt;em&gt;The Lancet Oncology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The incidence of severe neurotoxicity declined by more than 50% and gastrointestinal toxicity by about 80% compared with historical results with twice-weekly dosing, they found.&lt;/p&gt;
&lt;p&gt;The combination of melphalan and prednisone has constituted standard therapy for older patients with myeloma for more than 30 years. Clinical trials showed that adding thalidomide or bortezomib improved efficacy compared with the two-drug regimen.&lt;/p&gt;
&lt;p&gt;However, studies also have shown that VMP leads to high rates of severe peripheral neurotoxicity and gastrointestinal toxicity. Mateos and co-authors designed a trial aimed at maintaining the efficacy of bortezomib-based treatment and reducing the toxicity.&lt;/p&gt;
&lt;p&gt;Investigators at 63 Spanish centers enrolled patients ages 65 and older with newly diagnosed myeloma. All patients received one six-week cycle of bortezomib given twice a week, plus prednisone, and were randomized to either melphalan or thalidomide. The first cycle of therapy was followed by five additional five-week cycles of once-weekly bortezomib, plus prednisone and randomized therapy.&lt;/p&gt;
&lt;p&gt;Patients who completed induction therapy were randomized to bortezomib plus either prednisone or thalidomide for as long as three years.&lt;/p&gt;
&lt;p&gt;The primary endpoint was response rate during induction and maintenance.&lt;/p&gt;
&lt;p&gt;The trial began with 260 patients, 178 of whom completed all six cycles of induction therapy and were randomized to the two induction regimens.&lt;/p&gt;
&lt;p&gt;During induction, 81% of patients in the VTP group had partial responses or better, as did 80% of the VMP group. Complete response rates were 28% with VTP and 20% with VMP, a nonsignificant difference.&lt;/p&gt;
&lt;p&gt;Combining bortezomib with melphalan and prednisone (VMP) proved safer than the combination of bortezomib, thalidomide, and prednisone (VTP).&lt;/p&gt;
&lt;p&gt;VTP was associated with twice as many serious adverse events (31% versus 15%, &lt;em&gt;P&lt;/em&gt;=0.01) and a significantly higher discontinuation rate (17% versus 12%, &lt;em&gt;P&lt;/em&gt;=0.03).&lt;/p&gt;
&lt;p&gt;Grade 3+ toxicity included infection in 1% of VTP patients and 7% of VMP patients, cardiac events (8% versus 0), and peripheral neuropathy (7% versus 9%). Gastrointestinal toxicity occurred in 4% of patients in both groups.&lt;/p&gt;
&lt;p&gt;The complete-response rates after maintenance therapy increased to 42% with bortezomib-thalidomide and 39% with bortezomib-prednisone.&lt;/p&gt;
&lt;p&gt;Peripheral neuropathy occurred in 2% of the prednisone group and 7% of the thalidomide group. No grade 3+ hematologic toxicity occurred in either group.&lt;/p&gt;
&lt;p&gt;Median follow-up was 32 months. The patients had a median progression-free survival of 31 months and a median time to progression of 35 months. The three-year overall survival was 70%. Results were similar in both treatment groups.&lt;/p&gt;
&lt;p&gt;&quot;This regimen could represent a platform for further refinement of an optimized treatment of elderly patients with multiple myeloma,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;In an accompanying commentary, S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minn., said the findings have immediate applicability to clinical practice and provide &quot;important answers about how new agents such as bortezomib can be incorporated effectively in the overall treatment strategy.&quot;&lt;/p&gt;
&lt;p&gt;At least three other regimens have demonstrated efficacy in randomized trials involving older patients with myeloma, Rajkumar continued. Deciding how to choose among the options will not be simple.&lt;/p&gt;
&lt;p&gt;&quot;As exciting as the advances are, we are faced with the challenge of selecting from treatments with significantly different side-effect profiles and route of administration with the benefit of randomized trials,&quot; Rajkumar wrote.&lt;/p&gt;
&lt;p&gt;&quot;For now, the choice of a particular regimen in elderly patients with myeloma will need to be made by baseline comorbidities, cytogenetic risk factors, drug availability, and physician preference.&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;Mateos disclosed relationships with Millennium, Celgene, Ortho-Biotech. Several co-authors disclosed multiple relationships with commercial interests.&lt;/p&gt;&lt;p&gt;Rajkumar reported that he had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3101"
                     title="Benefit, Cost at Odds in Gastric CA (CME/CE)"
                     score="0.007"
                     href="http://www.medpagetoday.com/HematologyOncology/OtherCancers/tb/21806?impressionId=1283456783629"
                     
      Patients with advanced gastric cancer lived about three months longer when trastuzumab (Herceptin) was added to conventional chemotherapy, investigators in a multinational trial reported.&lt;br&gt;
&lt;br&gt;The addition of the targeted therapy also improved progression-free survival (PFS) by a little more than a month, according to their paper published online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;Despite the modest survival benefit, Yung-Jue Bang, MD, of Seoul National University in South Korea, and co-authors believe the combination warrants consideration as a new standard therapeutic option for patients with HER2-positive advanced gastric or gastroesophageal cancer.&lt;/p&gt;
&lt;p&gt;&quot;Therefore, patients with advanced gastric or gastroesophageal junction cancer with these tumor characteristics should be offered trastuzumab plus chemotherapy as a treatment option.&quot;&lt;/p&gt;
&lt;p&gt;However, authors of an invited commentary said the findings raise a moral question about the huge expenditure (possibly as much as $400 million worldwide) for such a modest benefit, particularly in countries with limited healthcare resources.&lt;/p&gt;
&lt;p&gt;&quot;What is the justification for introducing a treatment that might enable one individual to live a few months longer, but will consume, for each person treated, the total yearly health expenditure for scores of their fellow citizens?&quot; Alastair J. Munro, MD, and Paddy G. Niblock, MD, of Ninewells Hospital and Medical School in Dundee, Scotland, wrote.&lt;/p&gt;
&lt;p&gt;No single standard of care exists for treatment of advanced gastric cancer. A meta-analysis of phase II and III randomized clinical trials did show that combination chemotherapy improves outcomes (&lt;em&gt;J Clin Oncol&lt;/em&gt; 2006; 24: 2903-2909). Two- and three-drug combinations are widely used in the U.S. and Europe, the authors noted.&lt;/p&gt;
&lt;p&gt;Human epidermal growth factor receptor 2 (HER2) is overexpressed in as many as a third of gastric cancers, providing a rationale for evaluating trastuzumab, a monoclonal antibody that targets HER2. The rationale led to the phase III study reported by Bang and co-authors.&lt;/p&gt;
&lt;p&gt;Investigators in 24 countries enrolled patients with metastatic gastric or gastroesophageal cancer and HER2 overexpression confirmed by immunochemistry (IHC) or by gene amplification by fluorescence in-situ hybridization (FISH). Patients were randomized to cisplatin-based chemotherapy with or without trastuzumab.&lt;/p&gt;
&lt;p&gt;The primary endpoint was overall survival, as calculated from all randomized patients who received study medication at least once. The primary analysis included 584 patients.&lt;/p&gt;
&lt;p&gt;Median follow-up in the trastuzumab arm was 18.6 months and 17.1 months in the control arm.&lt;/p&gt;
&lt;p&gt;Patients treated with trastuzumab had a median overall survival of 13.8 months compared with 11.1 months in the control arm, representing a 26% reduction in the hazard ratio (&lt;em&gt;P&lt;/em&gt;=0.0046).&lt;/p&gt;
&lt;p&gt;Median progression-free survival was 6.7 months in the trastuzumab group and 5.5 months without trastuzumab (&lt;em&gt;P&lt;/em&gt;=0.0002).&lt;/p&gt;
&lt;p&gt;Overall response, time to progression, and duration of response all were improved in the trastuzumab arm compared with chemotherapy alone.&lt;/p&gt;
&lt;p&gt;The most common adverse events in both groups were nausea, vomiting, and neutropenia, which occurred in a similar percentage of patients in each group. Grade 3-4 adverse events occurred in 68% of each treatment group, and cardiac adverse events occurred in 6% of each group.&lt;/p&gt;
&lt;p&gt;The study might also have identified a subgroup of patients who appeared to benefit more than others.&lt;/p&gt;
&lt;p&gt;Three-fourths of the patients had high HER2 protein expression, defined as IHC 2+ and FISH positive or IHC 3+. An exploratory post-hoc analysis showed that patients with high HER2 protein expression had a median overall survival of 16 months with trastuzumab compared with 11.8 months in patients who had low protein expression.&lt;/p&gt;
&lt;p&gt;Munro and Niblock said the study raises issues that have become increasingly common in the &quot;globalization of research into the treatment of cancer.&quot; They likened the results of such trials to a &quot;hall of evidential mirrors.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If we presuppose that only randomized trials produce evidence of sufficient quality to support decisions about the allocation of scarce resources, there is a problem,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;There is a lot of evidence on the effects of adding expensive new drugs to conventional therapies, but little evidence for when older, less expensive interventions are combined. The evidence we have might not be the evidence we need, and the evidence that we need may never become available.&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 funded by F. Hoffman-La Roche.&lt;/p&gt;&lt;p&gt;Bang disclosed relationships with F. Hoffman-La Roche. Other co-authors disclosed mutliple relationships with commercial interests. Co-authors included employees of F. Hoffman-La Roche.&lt;/p&gt;&lt;p&gt;Niblock disclosed a relationship with Merck-Serono.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2855"
                     title="Most Older AML Patients May Want to Skip Intensive Chemo (CME/CE)"
                     score="-0.006"
                     href="http://www.medpagetoday.com/HematologyOncology/Leukemia/tb/21470?impressionId=1283456783629"
                     
      &lt;p&gt;The majority of patients 70 and older who have acute myeloid leukemia (AML) may not benefit from intensive chemotherapy, a single-center study showed.&lt;/p&gt;
&lt;p&gt;Nearly three-quarters (72%) of patients undergoing intensive therapy had at least one factor predictive of eight-week mortality  --  including age older than 80, poor performance status, at least three karyotypic abnormalities, or elevated creatinine, according to Hagop Kantarjian, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.&lt;/p&gt;
&lt;p&gt;These patients had an eight-week mortality rate of 31% to 71%, median survival ranging from 0.5 to 5.3 months, and a three-year survival rate of less than 8%.&lt;/p&gt;
&lt;p&gt;Patients with none of those factors, on the other hand, had an eight-week mortality rate of 16%, median survival of 11.3 months, and a three-year survival rate of 22%, the researchers reported online in &lt;em&gt;Blood&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The findings clearly show that at least some older patients can undergo intensive chemotherapy, which raises the question of whether they should, Kantarjian and his colleagues noted in their paper.&lt;/p&gt;
&lt;p&gt;&quot;The answer is not clear cut and depends on what the treating oncologist and the patient consider a reasonable risk for a reasonable benefit with intensive chemotherapy,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;Most would probably agree that an eight-week mortality of less than 10% to 20% to achieve a complete response rate of more than 40% and a three-year survival of more than 10% would be an acceptable benefit:risk ratio with intensive chemotherapy.&quot;&lt;/p&gt;
&lt;p&gt;Kantarjian and his colleagues set out to identify a subset of older patients with AML who would benefit from intensive chemotherapy.&lt;/p&gt;
&lt;p&gt;They looked at 446 patients 70 and older who had AML with 20% or more myeloblasts and who were treated with cytarabine-based intensive chemotherapy between 1990 and 2008.&lt;/p&gt;
&lt;p&gt;Excluding 16 patients who had favorable karyotypes, the complete response rate in the remaining 430 was a &quot;reasonable&quot; 45%, according to the researchers.&lt;/p&gt;
&lt;p&gt;However, four-week mortality was 26% and eight-week mortality was 36%. Median survival was 4.6 months and the survival rate at one, two, and three years was 28%, 16%, and 10%, respectively.&lt;/p&gt;
&lt;p&gt;The following four factors were associated with an increased likelihood of dying within the first eight weeks of treatment in a multivariate analysis (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for all): &lt;ul&gt; &lt;li&gt;Poor performance status (ECOG score of 2 to 4): OR 3.25&lt;/li&gt; &lt;li&gt;Age 80 and older: OR 2.31 &lt;/li&gt; &lt;li&gt;Complex karyotypes (with at least three abnormalities): OR 2.07&lt;/li&gt; &lt;li&gt;Creatinine greater than 1.3 mg/dL: OR 1.96&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The eight-week mortality rate increased as the number of factors a patient had increased. The complete response rate dropped at the same time (from 57% in those with none of those factors to 16% in those with at least three).&lt;/p&gt;
&lt;p&gt;The fact that the eight-week mortality rate was greater than 30% in the patients who had at least one of those predictive factors  --  nearly three-quarters of the patients  --  indicates that clinicians may want to consider lower-risk strategies, according to the researchers.&lt;/p&gt;
&lt;p&gt;&quot;It is reasonable that such patients ... would be considered for alternative investigational therapies,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Patients who share characteristics with those who had complete response rates above 50%, an eight-week mortality rate less than 20%, and median survival of 11.3 months, however, &quot;should be encouraged to undergo intensive chemotherapy in leukemia centers with expertise in intensive supportive care.&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 authors received research grants from Genzyme, Celgene, and Eisai.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2813"
                     title="Virtual Colonoscopy Misses Mark on Cost (CME/CE)"
                     score="-0.007"
                     href="http://www.medpagetoday.com/HematologyOncology/Chemotherapy/tb/21421?impressionId=1283456783629"
                     
      &lt;p&gt;Virtual colonoscopy is cost-effective only when priced lower than conventional colonoscopy or if it attracts a large unscreened population, according to computer models of colon cancer screening strategies.&lt;/p&gt;
&lt;p&gt;The models showed that Medicare patients would gain fewer life-years with CT colonography  --  CTC, or virtual colonoscopy  --  than with conventional colonoscopy performed every 10 years and about the same number afforded by flexible sigmoidoscopy performed every five years.&lt;/p&gt;
&lt;p&gt;If reimbursed at about $500, CT colonography every five years would be the most costly form of screening for colon cancer, according to Amy B. Knudsen, PhD, of Massachusetts General Hospital in Boston, and colleagues.&lt;/p&gt;
&lt;p&gt;The newer technology would become cost-effective only if the price per scan dropped to $205 or less or if adherence to CT colonography was 25% better compared with other tests, they reported online in the &lt;em&gt;Journal of the National Cancer Institute&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;&quot;Our results suggest that CT colonography screening every five years provides a benefit in terms of life-years gained compared with no screening and provides only slightly fewer life-years gained than colonoscopy screening every 10 years,&quot; they wrote in conclusion.&lt;/p&gt;
&lt;p&gt;&quot;If CT colonography screening is reimbursed at roughly the same rate as colonoscopy, the cost, relative to the benefit derived and to the availability and costs of other colorectal cancer screening tests, is too high for it to be a cost-effective screening strategy.&quot;&lt;/p&gt;
&lt;p&gt;Virtual colonoscopy and conventional colonoscopy have similar sensitivity for detecting adenomas 10 mm or larger. The former offers the attraction of being less invasive, although patients must still undergo extensive bowel preparation before CT colonography. Moreover, a suspicious lesion detected by CT colonography requires a patient to undergo colonoscopy for biopsy or to remove the lesion.&lt;/p&gt;
&lt;p&gt;Last year, the Centers for Medicare and Medicaid Services (CMS) &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/Medicare/14186&quot; target=&quot;_blank&quot; title=&quot;Medicare&amp;#8200;Finalizes&amp;#8200;Denial&amp;#8200;of&amp;#8200;Virtual&amp;#8200;Colonoscopy&amp;#8200;Coverage&quot;&gt;refused to cover CT colonography&lt;/a&gt; for its beneficiaries, finding the evidence inadequate to support approval for reimbursement. In preparation for making a coverage decision, CMS requested analyses of CT colonography screening among Medicare enrollees.&lt;/p&gt;
&lt;p&gt;Three members of the National Cancer Institute&apos;s Cancer Intervention and Surveillance Modeling Network performed analyses, including Knudsen and co-authors. The &lt;em&gt;JNCI&lt;/em&gt; article summarized the findings they reported to CMS.&lt;/p&gt;
&lt;p&gt;For the analysis, the authors used three independently developed microsimulation models to assess outcomes and costs associated with CT colonography performed every five years.&lt;/p&gt;
&lt;p&gt;They also compared the newer technology with screening tests already covered by Medicare: fecal occult blood test (FOBT), flexible sigmoidoscopy every five years with and without annual FOBT, and colonoscopy every 10 years.&lt;/p&gt;
&lt;p&gt;Assumptions included referral for colonoscopy for any suspicious lesions 6 mm or larger detected by CT colonography and perfect adherence to all screening modalities.&lt;/p&gt;
&lt;p&gt;The analyses showed that CT colonography would add 143 to 178 life-years per 1,000 65-year-olds screened. That compared with 152 to 185 life-years for conventional colonoscopy every 10 years, and 149 to 177 for flexible sigmoidoscopy every five years supplemented with annual FOBT.&lt;/p&gt;
&lt;p&gt;If CT colonography were reimbursed at $488  --  slightly less than colonoscopy without polypectomy  --  the imaging study would be the most costly of the screening options.&lt;/p&gt;
&lt;p&gt;The authors determined that virtual colonoscopy would be cost-effective with reimbursement of $108 to $205, depending on which model was used. The imaging study also would be cost-effective if it attracted a large proportion of patients who are currently not screened.&lt;/p&gt;
&lt;p&gt;Besides the inherent weaknesses of a computer model, the authors noted several other limitations to the study, including the fact that they did not consider risks and costs associated with radiation exposure in CTC or with the detection of findings outside the colon. Nor did they quality-adjust estimates of numbers of life-years.&lt;/p&gt;
&lt;p&gt;Some of their assumptions might also have skewed the results. They assumed, for instance, that all 65-year-olds were previously unscreened and that individuals kept to the screening schedule.&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 Agency for Healthcare Research and Quality.&lt;/p&gt;&lt;p&gt;The authors reported that they had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>
