<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_465"
                     title="Genetic Pathways Play Role in NSCLC Survival (CME/CE)"
                     score="0.014"
                     href="http://www.medpagetoday.com/HematologyOncology/LungCancer/tb/18396?impressionId=1265784275695"
                     
      Researchers say they&apos;ve found genetic characteristics associated with age and sex differences observed in recurrence-free survival among non-small cell lung cancer patients.&lt;br&gt;
&lt;br&gt;Older patients at higher risk for recurrence had increased activation of wound-healing and invasiveness pathways, while high-risk women had increased activation of invasiveness and &lt;em&gt;STAT3&lt;/em&gt; pathways, Anil Potti, MD, of Duke University, and colleagues reported in the Feb. 10 issue of the &lt;em&gt;Journal of the American Medical Association&lt;/em&gt;.&lt;br&gt;
&lt;br&gt;High-risk men had increased activation of the &lt;em&gt;STAT3&lt;/em&gt;, tumor necrosis factor, &lt;em&gt;EGFR&lt;/em&gt;, and wound-healing pathways, Potti the researchers found.&lt;br&gt;
&lt;br&gt;&quot;This analysis represents one of the first large-scale attempts to comprehensively characterize the biology of early-stage [non-small cell lung cancer] at a molecular pathway level and demonstrates a clear distinction in gene expression profiles within relevant age and sex categories,&quot; they wrote.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;There&apos;s lots of evidence that clinical and pathologic factors are clinically relevant, the researchers noted, but little is known about the underlying biological differences in lung tumor gene expression among patients with different characteristics, including age and gender.&lt;/p&gt;
&lt;p&gt;So Potti and colleagues conducted a retrospective analysis of 787 patients with predominantly early stage non-small cell lung cancer at Duke University from July 2008 to June 2009.&lt;/p&gt;
&lt;p&gt;They stratified their results by risk of recurrence, age, and gender.&lt;/p&gt;
&lt;p&gt;They found that high-risk patients under 70 had greater activation of the &lt;em&gt;Src&lt;/em&gt; and tumor necrosis factor pathways than low-risk patients (25% versus 6%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001; and 76% versus 42%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, respectively).&lt;/p&gt;
&lt;p&gt;In patients 70 and older, those at high risk for recurrence had greater activation of the wound-healing and invasiveness pathways than low-risk patients (40% versus 24%, &lt;em&gt;P&lt;/em&gt;=0.02; and 64% versus 20%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, respectively).&lt;/p&gt;
&lt;p&gt;&quot;Although this is a novel finding, biologically this is not entirely unexpected,&quot; the researchers wrote in reference to the data in older patients. &quot;The invasiveness and wound-healing gene signatures likely identify tumors at high risk of metastasis, along with the wound-healing signature identifying activation of angiogenesis pathways.&quot;&lt;/p&gt;
&lt;p&gt;Their findings also corroborated previous evidence that biology and clinical course of the disease are sex-specific, as the analysis found that women had significantly better progression-free survival than men (&lt;em&gt;P&lt;/em&gt;=0.008).&lt;/p&gt;
&lt;p&gt;In general, men had a higher probability of activation of these pathways than women:&lt;ul&gt;&lt;li&gt;Chromosomal instability (&lt;em&gt;P&lt;/em&gt;=0.001)&lt;/li&gt;&lt;li&gt;Epigenetic stem cell (&lt;em&gt;P&lt;/em&gt;=0.03)&lt;/li&gt;&lt;li&gt;Invasiveness (&lt;em&gt;P&lt;/em&gt;=0.005)&lt;/li&gt;&lt;li&gt;&lt;em&gt;Myc&lt;/em&gt; (&lt;em&gt;P&lt;/em&gt;=0.02)&lt;/li&gt;&lt;li&gt;Wound-healing (&lt;em&gt;P&lt;/em&gt;=0.004)&lt;/li&gt;&lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Women, meanwhile, had a higher probability of activation of the &lt;em&gt;E2F1&lt;/em&gt; pathway (&lt;em&gt;P&lt;/em&gt;=0.04).&lt;/p&gt;
&lt;p&gt;When stratified by risk, high-risk women had increased activation of the invasiveness and &lt;em&gt;STAT3&lt;/em&gt; pathways compared with low-risk women (99% versus 2%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001; and 72% versus 35%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001, respectively).&lt;/p&gt;
&lt;p&gt;Compared with low-risk men, those with high risk had increased activation of the following pathways:&lt;ul&gt;&lt;li&gt;&lt;em&gt;STAT3&lt;/em&gt; (87% versus 18%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt;&lt;li&gt;Tumor necrosis factor (90% versus 46%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) &lt;/li&gt;&lt;li&gt;&lt;em&gt;EGFR&lt;/em&gt; (13% versus 2%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt;&lt;li&gt;Wound-healing pathways (50% versus 22%, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001)&lt;/li&gt;&lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;Multivariate analyses confirmed pathway-based subphenotypes in women (HR 2.02, 95% CI 1.34 to 3.03, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) and in patients under 70 (HR 1.83, 95% CI 1.24 to 2.71, &lt;em&gt;P&lt;/em&gt;=0.003).&lt;/p&gt;
&lt;p&gt;&quot;While differences in clinical outcomes and the biology of [non-small cell lung cancer] based on age and sex have been previously noted, we were able to describe the molecular networks contributing to these differences,&quot; the researchers wrote.&lt;/p&gt;
&lt;p&gt;They said the findings are &quot;apt for therapeutic interventions when planning clinical trials with drugs that target specific pathway-related abnormalities or tumor biology.&quot;&lt;/p&gt;
&lt;p&gt;&quot;With genomic assays now being increasingly practical and clinically applicable, with turnaround times of five to seven days,&quot; they concluded, &quot;we believe our findings, while hypothesis generating and needing further validation, represent a step forward in defining pathway-driven cohorts of [non-small cell lung cancer] that likely explain the age-and sex-specific differences.&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 grants from the Emilene Brown Cancer Research Fund, the Harold and Linda Chapman Lung Cancer Fund, the Jimmy V Foundation, the American Cancer Society, and the National Cancer Institute.&lt;/p&gt;&lt;p&gt;The researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_406"
                     title="AAPM: Opioid Gains Long-Term Control of Neuropathic Cancer Pain (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/MeetingCoverage/AAPM/tb/18316?impressionId=1265784275695"
                     
      &lt;p&gt;SAN ANTONIO  --  Patients with neuropathic cancer pain obtained consistent, long-term pain control with extended-release oxymorphone (Opana), according to results of a one-year, open-label extension study.&lt;/p&gt;
&lt;p&gt;Patients reported pain in the mild range throughout most of the follow-up, and only 11% discontinued because of lack of efficacy, Errol Gould, PhD, of Endo Pharmaceuticals in Chadds Ford, Pa., reported here at the American Academy of Pain Medicine meeting. The company manufactures Opana.&lt;/p&gt;
&lt;p&gt;No unexpected adverse events occurred.&lt;/p&gt;
&lt;p&gt;&quot;Current clinical guidelines recommend opioids as second- or third-line treatment for chronic neuropathic pain,&quot; Gould said in an interview. &quot;These results suggest that oxymorphone extended release may be a viable long-term option for patients with neuropathic pain.&quot;&lt;/p&gt;
&lt;p&gt;The findings came from a one-year extension of a multicenter, open-label, noncontrolled short-term study of patients with cancer-related chronic pain.&lt;/p&gt;
&lt;p&gt;Of 44 patients who entered the extension phase, 27 had pain that was primarily neuropathic in origin. The diagnosis of neuropathic pain was based on clinician judgment, with no prespecified diagnostic criteria for guidance.&lt;/p&gt;
&lt;p&gt;Patients began treatment in the extension phase with their ending dose from the short-term study. Dose adjustments to improve pain control or tolerability were allowed throughout the 52-week extension phase.&lt;/p&gt;
&lt;p&gt;Ten of the 27 patients completed the extension study. Principal reasons for withdrawal were adverse events, patient request, loss of effectiveness, and nonadherence.&lt;/p&gt;
&lt;p&gt;The median duration from initiation of long-term maintenance to final visit was 22 weeks. Baseline pain intensity averaged 32.9 on a 100-point scale and 32.6 at final visit. Mean least pain intensity was 13.8 at baseline and 16.2 at final visit, and worst pain intensity averaged 76.3 at baseline and 66.5 at final visit.&lt;/p&gt;
&lt;p&gt;&quot;Regression analysis showed that pain intensity changed very little throughout follow-up,&quot; Gould said.&lt;/p&gt;
&lt;p&gt;The median oxymorphone dose increased from 80 mg at baseline to 160 mg at 52 weeks.&lt;/p&gt;
&lt;p&gt;Eleven (41%) patients reported at least one treatment-related adverse event. The most common events were dry mouth, constipation, and fatigue. The only serious adverse event was an episode of depressed consciousness.&lt;/p&gt;
&lt;p&gt;&quot;Patients required some gradual increases in dosage over time, but that&apos;s consistent with the nature of the disease,&quot; said Gould.&lt;/p&gt;
&lt;p&gt;Not long ago opioids were considered ineffective for neuropathic pain, he added. This study provided additional evidence in support of opioids&apos; effectiveness in controlling neuropathic pain.&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 Endo Pharmaceuticals, which manufactures Opana.&lt;/p&gt;&lt;p&gt;Gould and another co-author are employees of Endo Pharmaceuticals.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_398"
                     title="ASCO GI: Gene Test, Nodes Predict Colon CA Recurrence Risk (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18301?impressionId=1265784275695"
                     
      &lt;p&gt;ORLANDO  --  An extended nodal examination and gene array test show promise for identifying patients at high risk of colorectal cancer recurrence in stage II disease, researchers reported at the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;Across the range of recurrence scores, examination of at least 12 nodes was associated with about a 5% absolute decrease in the three-year risk of recurrence in resected stage II colon cancers, compared with the same recurrence score and examination of fewer nodes.&lt;/p&gt;
&lt;p&gt;Noting limitations of other tests and biomarkers developed to evaluate recurrence risk, the gene expression-derived recurrence score &quot;has a real chance to make its way into the clinical decision algorithm,&quot; said David Kerr, MD, of the University of Oxford in England.&lt;/p&gt;
&lt;p&gt;Both recurrence score and number of nodes examined were independent predictors of recurrence risk, but investigators found no association or interaction between the two parameters of risk assessment.&lt;/p&gt;
&lt;p&gt;&quot;The test gives us more information about individual patients about the likelihood of the cancer returning,&quot; said Kerr, who was an investigator in the study. &quot;I think the quality of the science underpinning it, the size of the sample, and the compelling statistics all combine to make this a potential winner.&quot;&lt;/p&gt;
&lt;p&gt;Another study reported at the meeting showed few tumor-related genetic characteristics to distinguish stage II colon cancer from stage III.&lt;/p&gt;
&lt;p&gt;Both studies involved use a 12-gene assay (Oncotype DX) validated for predicting recurrence risk in stage II colon cancer. Investigators in the QUASAR validation study used data from the trial to evaluate the prognostic value of nodal assessment combined with other parameters, including the 12-gene assay.&lt;/p&gt;
&lt;p&gt;The National Comprehensive Cancer Network (NCCN) clinical guidelines for stage II colon cancer include number of nodes examined as a prognostic factor, Richard Gray, PhD, of the University of Birmingham in England, and colleagues noted in a poster presentation.&lt;/p&gt;
&lt;p&gt;Records for 657 stage II patients randomized to surgery alone showed that the median number of nodes examined was 10, including fewer than six nodes in 19% of patients and &amp;#8805;12 nodes in 37%. Risk of recurrence was more closely associated with examination of fewer than eight nodes versus more (HR 1.77, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001) than with a cutoff point of 12 nodes (HR 1.38, &lt;em&gt;P&lt;/em&gt;=0.065). &lt;/p&gt;
&lt;p&gt;More nodes were examined in later than earlier years, the investigators found.&lt;/p&gt;
&lt;p&gt;In a model that included recurrence score derived from the gene assay and the 12-node threshold recommended by NCCN, both factors proved to be independent predictors of recurrence risk (&lt;em&gt;P&lt;/em&gt;=0.01, &lt;em&gt;P&lt;/em&gt;=0.05). Similar results emerged from models that incorporated mismatch repair (or microsatellite instability) and T stage.&lt;/p&gt;
&lt;p&gt;Across the range of recurrence scores, examination of &amp;#8805;12 nodes was associated with a 3% to 7% lower risk of recurrence compared with examination of fewer nodes (about 5% overall). The investigators concluded that both parameters should be included in assessment of recurrence risk after surgery for stage II colon cancer.&lt;/p&gt;
&lt;p&gt;The second study examined the 12-gene assay&apos;s ability to distinguish stage II from stage III colon cancer. Investigators evaluated the assay, pathologic markers, and expression of 375 different genes in 634 patients with stage II disease and 844 with stage III colon cancer.&lt;/p&gt;
&lt;p&gt;The data showed minimal differences in gene expression between the two stages of colon cancer.&lt;/p&gt;
&lt;p&gt;Five of the 375 genes differed significantly in their expression in stage II versus stage III cancer (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05). Two tumor characteristics differed by stage, as stage II colon cancer was more likely to be mismatch repair-deficient (&lt;em&gt;P&lt;/em&gt;=0.04) and have mucinous histology (&lt;em&gt;P&lt;/em&gt;=0.007).&lt;/p&gt;
&lt;p&gt;The data also showed significant interaction of grade and stage (&lt;em&gt;P&lt;/em&gt;=0.005), and borderline significance for interactions of stage with T-stage, mismatch repair, and mucinous histology, reflecting prognostic value in stage II but not stage III disease.&lt;/p&gt;
&lt;p&gt;Overall, investigators in this second study found a &quot;striking similarity between stages for the recurrence score and the vast majority of genes analyzed.&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 studies were supported by Genomic Health.&lt;/p&gt;&lt;p&gt;Investigators in the studies included employees of Genomic Health.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_260"
                     title="ASCO GI: Agent Targets IGF Receptor in Pancreatic Cancer (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18124?impressionId=1265784275695"
                     
      &lt;p&gt;ORLANDO  --  A majority of patients with advanced pancreatic cancer had objective responses or stable disease when treated with an inhibitor of the insulin-like growth factor (IGF) receptor, according to data from a small clinical trial reported here.&lt;/p&gt;
&lt;p&gt;A fourth of patients had partial responses that lasted beyond 11 months in some cases. Another third had disease stabilization during treatment with the monoclonal antibody MK-0646, plus chemotherapy and erlotinib (Tarceva).&lt;/p&gt;
&lt;p&gt;&quot;We observed sustained partial responses with two different regimens,&quot; Milind Javle, MD, of M.D. Anderson Cancer Center in Houston, told attendees at the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;&quot;Evaluation of MK-0646 is continuing in a randomized phase II study that will include correlative studies to identify predictive markers.&quot;&lt;/p&gt;
&lt;p&gt;Activation of the IGF-1 receptor is associated with an aggressive disease course in pancreatic cancer and acquired resistance to agents that target epidermal growth factor receptor (EGFR) such as erlotinib.&lt;/p&gt;
&lt;p&gt;&lt;/p&gt;
&lt;p&gt; &lt;/p&gt;
&lt;p&gt;Preclinical studies showed that combining an IGF-1 receptor antagonist and cetuximab (Erbitux) had synergistic activity against pancreatic cell lines, Javle said.&lt;/p&gt;
&lt;p&gt;MK-0646 preferentially binds IGF-1 receptor and not the insulin receptor. The antibody inhibits stimulation of IGF-1 receptor by both IGF-1 and IGF-2, Javle continued. MK-0646 downregulates expression of IGF-1 receptor in tumor models and has demonstrated antitumor activity in xenograft models.&lt;/p&gt;
&lt;p&gt;Phase I evaluation of MK-0646 as a single agent showed the antibody was well tolerated and led to downregulation of IGF-1 receptor and other molecules associated with tumor growth. Patients occasionally developed hyperglycemia, which was controlled with oral hypoglycemic agents.&lt;/p&gt;
&lt;p&gt;Javle reported data from a phase I-II study of MK-0646 in combination with gemcitabine (Gemzar) or gemcitabine plus erlotinib. The primary objective of the first phase was to determine the maximum tolerated dose of MK-0646 in combination therapy. Investigators assessed progression-free survival (PFS) of the two combination arms in the second phase.&lt;/p&gt;
&lt;p&gt;The study included patients with stage IV pancreatic adenocarcinoma at least six months after completion of adjuvant chemotherapy.&lt;/p&gt;
&lt;p&gt;Patients were enrolled in a nonrandomized, sequential manner to two treatment arms. One arm had a regimen consisting of weekly gemcitabine plus weekly MK-0646 at either 5 mg/kg or 10 mg/kg. In the second arm, patients received gemcitabine plus daily erlotinib and one of the two doses of MK-0646.&lt;/p&gt;
&lt;p&gt;Dose-limiting hematologic toxicity was defined as grade 4 thrombocytopenia, grade 4 neutropenia lasting at least seven days, or grade 3 or higher neutropenia with fever.&lt;/p&gt;
&lt;p&gt;Dose-limiting nonhematologic toxicity was defined as any grade 3-4 adverse event except rash and controlled hyperglycemia. Delayed dosing was defined as a delay of more than 14 days necessitated by toxicity.&lt;/p&gt;
&lt;p&gt;Of 28 patients enrolled in the study, 23 (82%) required dose adjustment of gemcitabine, and seven had toxicity-associated dose adjustments of erlotinib. Five patients discontinued erlotinib because of toxicity, but no patient withdrew from the study because of toxicity.&lt;/p&gt;
&lt;p&gt;The most frequent grade 3-4 nonhematologic toxicities were hyperglycemia and fatigue (five patients each) and elevated liver enzymes and hypermagnesemia (four each). Half the patients developed grade 3-4 neutropenia and five had grade 3-4 thrombocytopenia. No cases of febrile neutropenia occurred.&lt;/p&gt;
&lt;p&gt;Maximum tolerated dose (MTD) in the first arm was not reached at the 10 mg/kg dose of MK-0646. In the erlotinib arm, MTD was reached at the 5 mg/kg dose of MK-0646.&lt;/p&gt;
&lt;p&gt;Of 24 patients evaluable for response, six (25%) had partial responses and eight (33%) had stable disease. The remaining 10 patients had progressive disease. Response duration ranged from 14 to beyond 44 weeks. Time to progression did not differ between the treatment arms.&lt;/p&gt;
&lt;p&gt;A randomized phase II study of MK-0646 has already begun, said Javle. Patients receive one of three treatment regimens: gemcitabine plus the monoclonal antibody, with or without erlotinib, or control therapy with gemcitabine and erlotinib.&lt;/p&gt;
&lt;p&gt;The activity demonstrated in the study does not constitute an antitumor signal for MK-0646, Philip A. Philip, MD, of the Karmanos Cancer Center in Detroit, said during a formal discussion of the study.&lt;/p&gt;
&lt;p&gt;&quot;Further preclinical and clinical validation of and IGF-1 receptor-based multitargeted strategy in pancreatic cancer must be undertaken,&quot; he said. &quot;Additionally, predictive biomarkers must be developed for patient selection and stratification. We need more data before we begin to design a phase III study.&quot;&lt;/p&gt;
&lt;p&gt;Hyperglycemia with MK-0646 should not come as a surprise, Philip said. The IGF-1 receptor occurring on normal cells has 84% homology with insulin receptor.&lt;/p&gt;
&lt;p&gt;&quot;There will be overlap between IGF-1 receptor and insulin receptor when targeting IGF-1 receptor,&quot; said Philip. &quot;Moreover, up to 40% of patients with pancreatic cancer have diabetes mellitus.&quot;&lt;/p&gt;
&lt;p&gt;In an ongoing intergroup trial involving a different IGF-1 receptor inhibitor, almost half the patients developed grade 1 or 2 hyperglycemia, and 14% developed grade 3 or 4, he added. However, hyperglycemia does not appear to be a dose-limiting toxicity.&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 Merck.&lt;/p&gt;&lt;p&gt;One or more investigators in the study disclosed relationships with Merck.&lt;/p&gt;&lt;p&gt;Philip disclosed relationships with Bristol-Myers Squibb, ImClone, OSIP, sanofi-aventis, Genentech, Pfizer, Lilly, and Roche.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_276"
                     title="ASCO GI: Antibody Slows Metastatic Colon Cancer"
                     score="0.001"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18134?impressionId=1265784275695"
                     
      ORLANDO  --  Patients with nonmutated colorectal tumors had significant improvement in progression-free survival (PFS) when the monoclonal antibody panitumumab (Vectibix) was added to conventional chemotherapy, data from two randomized clinical trials showed.&lt;br&gt;
&lt;br&gt;When used in first-line therapy for metastatic cancer, the antibody-chemotherapy combination was associated with a 20% improvement in the hazard ratio for progression compared with chemotherapy alone. In the second-line metastatic setting, the combination improved the hazard ratio by 27%.&lt;br&gt;
&lt;br&gt;Separate analyses of the trials showed that the addition of panitumumab to chemotherapy did not improve PFS in patients whose tumors had K-ras mutations.&lt;br&gt;
&lt;br&gt;Overall survival was similar between treatment arms in both trials, according to presentations here at the Gastrointestinal Cancers Symposium.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;The results of these two studies are consistent in that they demonstrate a benefit from the addition of panitumumab among patients with wild-type K-ras tumors,&quot; Salvatore Siena, MD, of Ospedale Niguarda Ca&apos;Granda in Milan, Italy, said in an interview. &quot;The results also are consistent with what we know about the role of K-ras in colorectal cancer.&quot;&lt;/p&gt;
&lt;p&gt;&quot;The addition of panitumumab to the chemotherapy regimens used in the studies was well tolerated, as no unexpected toxicity was observed,&quot; he added.&lt;/p&gt;
&lt;p&gt;Panitumumab is a fully human monoclonal antibody against epidermal growth factor receptor (EGFR). The agent is approved for treatment of chemotherapy-refractory metastatic colorectal cancer.&lt;/p&gt;
&lt;p&gt;The two clinical trials initially were designed to evaluate panitumumab in all patients, irrespective of K-ras status. Following reports about the adverse effect of K-ras mutations on therapeutic outcomes in colorectal cancer, the trials&apos; protocols were amended to test the hypothesis that adding panitumumab to chemotherapy would improve PFS in patients with wild-type K-ras status.&lt;/p&gt;
&lt;p&gt;The trial of first-line metastatic therapy compared panitumumab plus 5-FU/leucovorin/oxaliplatin (Eloxatin) chemotherapy versus chemotherapy (FOLFOX) alone. The open-label, randomized trial involved 1,183 patients enrolled at centers in Canada, South America, Europe, South Africa, and Australia.&lt;/p&gt;
&lt;p&gt;The primary endpoint was PFS, and secondary endpoints included overall survival, overall response rate, time to response, duration of response, and safety. The protocol excluded patients with prior chemotherapy for metastatic colorectal cancer or prior EGFR inhibitor therapy.&lt;/p&gt;
&lt;p&gt;Tissue samples were collected for biomarker assessment, but EGFR and K-ras status assessment were not required at entry. Siena said K-ras status was ascertained in 93% of the patients and showed that 60% of both treatment arms had wild-type K-ras tumors.&lt;/p&gt;
&lt;p&gt;In the primary analysis involving patients with wild-type K-ras tumors, the addition of panitumumab to FOLFOX was associated with a PFS of 9.6 months compared with 8.0 months for patients treated with chemotherapy alone (HR 0.80, 95% CI 0.66 to 0.97, &lt;em&gt;P&lt;/em&gt;=0.02). Addition of the antibody was associated with a trend toward improved overall survival (23.9 months versus 19.7 months, &lt;em&gt;P&lt;/em&gt;=0.07) and overall response rate (55% versus 48%, &lt;em&gt;P&lt;/em&gt;=0.07).&lt;/p&gt;
&lt;p&gt;Patients with mutant-type K-ras tumors fared better with chemotherapy alone, which led to a median PFS of 8.8 months versus 7.3 months for chemotherapy plus panitumumab (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;Similar results emerged from the study of second-line therapy for metastatic cancer, reported by Marc Peeters, MD, of University Hospital Ghent in Belgium.&lt;/p&gt;
&lt;p&gt;The trial involved 1,186 patients who had previously received chemotherapy for metastatic colorectal cancer enrolled at centers in the U.S., Europe, Asia, and Australia. As in the study of first-line therapy, about 60% of the patients had wild-type K-ras tumors.&lt;/p&gt;
&lt;p&gt;The trial compared FOLFIRI chemotherapy (5-FU/leucovorin/irinotecan [Camptosar]) alone versus FOLFIRI plus panitumumab.&lt;/p&gt;
&lt;p&gt;Among patients with wild-type K-ras tumors, the addition of panitumumab was associated with a median PFS of 5.9 months versus 3.9 months for chemotherapy alone (HR 0.73, 95% CI 0.59 to 0.90, &lt;em&gt;P&lt;/em&gt;=0.004).&lt;/p&gt;
&lt;p&gt;Median overall survival was 14.5 months with the monoclonal antibody and 12.5 months without, a difference that did not reach statistical significance. The overall response rate was significantly higher in the panitumumab arm (35% versus 10%, &lt;em&gt;P&lt;/em&gt;=0.001).&lt;/p&gt;
&lt;p&gt;As in the first-line study, patients with mutant K-ras tumors did not benefit from the addition of panitumumab, which was associated with a median PFS of 5.0 months versus 4.9 months with chemotherapy alone. Overall survival was 11.8 months with panitumumab and 11.1 months without it, a nonsignificant difference.&lt;/p&gt;
&lt;p&gt;The panitumumab regimen was generally well tolerated in both studies. The principal difference in adverse events was an excess of skin toxicity with panitumumab, a recognized side effect of the monoclonal antibody.&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;Both studies were supported by Amgen.&lt;/p&gt;&lt;p&gt;One or more investigators in the studies disclosed relatinships with Amgen, Merck Serono, Roche, Baxter International, Merck &amp;amp; Co., Roche, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, ImClone Slystems, sanofi-aventis, and Pfizer.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>