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    <recommendedItem id="20100101_19_357"
                     title="Targeted Therapy Disappoints in Recurrent Brain Tumors (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/HematologyOncology/BrainCancer/tb/18237?impressionId=1265784681951"
                     
      &lt;p&gt;High hopes for treating recurrent glioblastoma with the novel, targeted antiangiogenic enzastaurin have been diminished by disappointing phase III results.&lt;/p&gt;
&lt;p&gt;The study failed its primary endpoint with a median progression-free survival of 1.5 months compared with 1.6 months on conventional lomustine (CeeNu, &lt;em&gt;P&lt;/em&gt;=0.08).&lt;/p&gt;
&lt;p&gt;Nor were there any other significant benefits, despite generally good tolerability, Wolfgang Wick, MD, of the University of Heidelberg, Germany, and colleagues reported online in the &lt;em&gt;Journal of Clinical Oncology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;In an earlier &lt;a href=&quot;http://www.medpagetoday.com/HematologyOncology/BrainCancer/1062&quot; mce_href=&quot;http://www.medpagetoday.com/HematologyOncology/BrainCancer/1062&quot; target=&quot;_blank&quot;&gt;phase II study&lt;/a&gt;, the drug shrank tumors in 22% of heavily pretreated patients with recurrent glioblastoma, a heavily vascular cancer and one of the toughest to treat.&lt;/p&gt;
&lt;p&gt;The experimental agent is a potent and selective inhibitor of protein kinase C-beta, which mediates the most important regulator of vessel growth in glioma.&lt;/p&gt;
&lt;p&gt;Even so, jumping directly into a phase III study before the final results of a phase II study might have been premature, even with a strong preclinical rationale, the authors and an accompanying editorial said.&lt;/p&gt;
&lt;p&gt;Evanthia Galanis, MD, DSc, and Jan C. Buckner, MD, both of the Mayo Clinic in Rochester, Minn., wrote in an editorial that response rate &quot;can be particularly misleading as an indicator of antitumor activity of antiangiogenic agents.&quot;&lt;/p&gt;
&lt;p&gt;Reduced vascular permeability can appear as improvement on enhanced MRI, without true antitumor effect, the editorialists noted. Nor does response rate correlate well with progression-free or overall survival in this type of cancer, they wrote.&lt;/p&gt;
&lt;p&gt;Still, they cautioned, these negative phase III results aren&apos;t the final word on the drug whose modest activity was comparable to standard treatment  --  and with satisfactory tolerability.&lt;/p&gt;
&lt;p&gt;&quot;It would therefore still be worth incorporating enzastaurin in rationally designed combinatorial regimens, especially if based on a strong mechanistic rationale or preclinical demonstration of synergistic activity,&quot; Galanis and Buckner wrote.&lt;/p&gt;
&lt;p&gt;The study randomized patients with World Health Organization grade 4 glioblastoma to receive six-week cycles of open-label enzastaurin 500 mg/d (1,125-mg loading dose on day one) or lomustine (100 to 130 mg/m&lt;sup&gt;2&lt;/sup&gt; on day one).&lt;/p&gt;
&lt;p&gt;It was stopped at the planned interim futility analysis after enrollment of 266 patients.&lt;/p&gt;
&lt;p&gt;The researchers had powered the study for a 45% improvement in median progression-free survival, but found it actually tended to be 28% better with lomustine (HR 1.28, 95% CI 0.97 to 1.70).&lt;/p&gt;
&lt;p&gt;Six-month progression-free survival rates were 11.1% with the experimental treatment, compared with 19.0% among controls (&lt;em&gt;P&lt;/em&gt;=0.13).&lt;/p&gt;
&lt;p&gt;Overall survival, too, was similar at 6.6 and 7.1 months, respectively (HR 1.20, &lt;em&gt;P&lt;/em&gt;=0.25). Objective response rate showed no differences either (&lt;em&gt;P&lt;/em&gt;=0.501).&lt;/p&gt;
&lt;p&gt;Patient-reported time to deterioration  --  measured on the Functional Assessment of Cancer Therapy&amp;#8211;Brain questionnaire  --  was 2.27 months with enzastaurin compared with 2.33 months for lomustine (&lt;em&gt;P&lt;/em&gt;=0.54).&lt;/p&gt;
&lt;p&gt;Results likewise were similar between the groups for physical and functional well-being and for brain tumor&amp;#8211;specific concerns (&lt;em&gt;P&lt;/em&gt;&amp;gt;0.05).&lt;/p&gt;
&lt;p&gt;Adverse event rates were not different between groups, although more were drug-related in the lomustine group (62% versus 44%, &lt;em&gt;P&lt;/em&gt;=0.008).&lt;/p&gt;
&lt;p&gt;Enzastaurin did have the advantage of less hematologic toxicity overall (&lt;em&gt;P&lt;/em&gt;&amp;#8804;0.001), and specifically for grade 3 to 4 adverse events (one versus 46 events, &lt;em&gt;P&lt;/em&gt;&amp;#8804;0.001).&lt;/p&gt;
&lt;p&gt;Study deaths in the enzastaurin group totaled 11, including four due to adverse events and one drug-related; while the four deaths in lomustine-treated patients were disease-related.&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 Eli Lilly, including writing and editorial support.&lt;/p&gt;&lt;p&gt;Wick and co-authors reported financial conflicts of interest with Eli Lilly, including employment and stock ownership for some.&lt;/p&gt;&lt;p&gt;Co-authors also reported financial conflicts of interest with Merck, Genentech, Enzon, Schering-Plough, and AstraZeneca.&lt;/p&gt;&lt;p&gt;Galanis reported conflicts of interest with Merck, Bristol-Myers Squibb, Gradalis, Genetech, and Bayer Pharmaceuticals.&lt;/p&gt;&lt;p&gt;Buckner reported conflicts of interest with Merck Serono, Genentech, Excelixis, Bayer Pharmaceuticals, Bristol-Myers Squibb, and Anti-Sense Pharma.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_345"
                     title="FDA Okays Drug Combo for Advanced Breast Cancer"
                     score="0.007"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/18224?impressionId=1265784681951"
                     
      &lt;p&gt;The FDA has approved a combination of lapatinib (Tykerb) and letrozole (Femara) to treat hormone-positive and HER2-positive advanced breast cancer in postmenopausal women.&lt;/p&gt;
&lt;p&gt;The approval follows a company-sponsored study that found that women with HER2-positive disease who were taking the combination had survival rates more than double that of women on letrozole alone (35 weeks versus 13 weeks).&lt;/p&gt;
&lt;p&gt;Lapatinib is an oral kinase inhibitor that blocks the function of the HER2-positive protein. In 2007, it was approved in combination with capecitabine (Xeloda) to treat advanced HER2-positive breast cancer tumors in refractory disease. (See &lt;a href=&quot;http://www.medpagetoday.com/HematologyOncology/Chemotherapy/5247&quot; mce_href=&quot;http://www.medpagetoday.com/HematologyOncology/Chemotherapy/5247&quot; target=&quot;_blank&quot;&gt;FDA Okays Lapatinib (Tykerb) for Treatment-Resistant Breast Cancer&lt;/a&gt;).&lt;/p&gt;
&lt;p&gt;The FDA said the most commonly reported side effects of the lapatinib/letrozole combination were diarrhea, rash, nausea, and fatigue.&lt;/p&gt;
&lt;p&gt;Treatment with lapatinib has also been associated with decreased heart function, liver damage, and inflammation of lung tissue, the agency cautioned. It may also cause harm to the fetus if used in pregnant women.&lt;/p&gt;
&lt;p&gt;Richard Pazdur, MD, director of the FDA&apos;s office of oncology drug products, said in a prepared statement that the combination &quot;provides women being treated for advanced breast cancer with an important treatment option.&quot;&lt;/p&gt;
&lt;p&gt;Lapatinib is marketed by GlaxoSmithKline and letrozole by Novartis AG.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_298"
                     title="FDA Updates Myeloma Drug Label for New Risks"
                     score="0.002"
                     href="http://www.medpagetoday.com/ProductAlert/DevicesandVaccines/tb/18158?impressionId=1265784681951"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has revised dosage and safety information for bortezomib (Velcade), the myeloma and mantle cell lymphoma drug, to reflect an increased toxicity risk.&lt;/p&gt;
&lt;p&gt;The new labeling includes a warning for patients with moderate-to-severe hepatic impairment and now recommends at-risk patients start at a lower dosage of 0.7 mg for the first cycle of treatment and escalate to 1.0 mg, or reduce further to 0.5 mg, in subsequent cycles.&lt;/p&gt;
&lt;p&gt;The label has also been updated to include clinical study data showing a higher median survival rate in patients using a combination of bortezomib, melphalan, and prednisone versus a regiment of just melphalan and prednisone (&lt;em&gt;P&lt;/em&gt;=0.00084).&lt;/p&gt;
&lt;p&gt;The drug is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol. The FDA also warns that women should avoid becoming pregnant while undergoing treatment with bortezomib.&lt;/p&gt;
&lt;p&gt;The drug is manufactured by Millennium: The Takeda Oncology Company of Cambridge, Mass.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20100101_19_252"
                     title="MS Walking Drug Gets FDA Nod"
                     score="-0.002"
                     href="http://www.medpagetoday.com/Neurology/MultipleSclerosis/tb/18112?impressionId=1265784681951"
                     
      &lt;p&gt;WASHINGTON  --  The FDA has approved the first drug that improves walking in patients with multiple sclerosis, the tablet dalfampridine (Ampyra).&lt;/p&gt;
&lt;p&gt;The approval was based on clinical trial data that found patients could walk better with the drug than those treated with placebo.&lt;/p&gt;
&lt;p&gt;Patients who exceed recommended dosage, 10 mg twice a day, or who have moderate to severe kidney disease, may experience seizures the FDA said.&lt;/p&gt;
&lt;p&gt;Adverse events reported during clinical trials include urinary tract infection, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling of the nose or throat, constipation, diarrhea, indigestion, throat pain, and burning, tingling, or itching skin.&lt;/p&gt;
&lt;p&gt;The drug is manufactured by Elan of Dublin, Ireland and distributed by Acorda Therapeutics Inc. of Hawthone, NY.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20090101_19_1006"
                     title="Bevacizumab Gets FDA Panel&apos;s Nod for Glioblastoma Multiforme"
                     score="-0.006"
                     href="http://www.medpagetoday.com/ProductAlert/Prescriptions/tb/13542?impressionId=1265784681951"
                     
       SILVER SPRING, Md., March 31 -- The FDA&apos;s advisory panel on cancer drugs recommended accelerated approval for bevacizumab (Avastin) as a treatment for glioblastoma multiforme, the notoriously deadly form of brain cancer.
              &lt;p&gt; 
              &lt;p&gt;The drug&apos;s manufacturer, Genentech, wants to market it as monotherapy for glioblastoma patients who have failed other therapies.
              &lt;p&gt; 
              &lt;p&gt;The Oncologic Drugs Advisory Committee voted 10-0 today that the results of two small pilot studies were adequate to support the fast-track approval, even as Genentech gears up for a larger confirmation study.
              &lt;p&gt; 
              &lt;p&gt;In one of the studies, bevacizumab monotherapy in 85 patients led to partial responses in 26% (95% CI 16% to 38%), with median response duration of 4.2 months. There were no complete responses. 
              &lt;p&gt; 
              &lt;p&gt;The six-month progression free-survival rate was 36% (95% CI 24% to 48%) and one-year overall survival was about 38%.
              &lt;p&gt; 
              &lt;p&gt;In contrast, the one-year survival rate among glioblastoma patients undergoing salvage chemotherapy following initial treatment failure is about 25%, according to Genentech&apos;s presentation.
              &lt;p&gt; 
              &lt;p&gt;The other study, involving 56 patients with previously treated, high-grade gliomas, yielded an objective response rate of 20% (95% CI 11% to 31%) with median duration of response of 3.9 months.
              &lt;p&gt; 
              &lt;p&gt;Going into the meeting, FDA staff reviewers were concerned about two aspects of the data. One was whether the studies&apos; assessments of tumor response were valid, given past difficulties in measuring tumor size with MRI scans.
              &lt;p&gt; 
              &lt;p&gt;The other issue was whether the apparent efficacy was an artifact of the drug&apos;s effects on tumor capillary permeability around glioblastoma tumors. Bevacizumab may alter the blood-brain barrier, leading to reduced peritumoral edema, and improved contrast enhancement in MRI scans.
              &lt;p&gt; 
              &lt;p&gt;The FDA review suggested that the study findings may not reflect a true anti-tumor effect.
              &lt;p&gt; 
              &lt;p&gt;But the panel dismissed those concerns, agreeing with Genentech that the data supported the accelerated approval.
              &lt;p&gt; 
              &lt;p&gt;One panel member called the study results &quot;dramatic.&quot;
              &lt;p&gt; 
              &lt;p&gt;The FDA is not required to follow advisory committee recommendations but usually does. A final agency decision is expected by early May.
              &lt;p&gt; 
              &lt;p&gt;Bevacizumab is currently approved for treating non-small cell lung cancer and metastatic colorectal and breast cancer as part of combination regimens.
    </recommendedItem>
</recommendedContent>