<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_276"
                     title="ASCO GI: Antibody Slows Metastatic Colon Cancer"
                     score="0.004"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18134?impressionId=1265740816432"
                     
      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>
    <recommendedItem id="20100101_19_260"
                     title="ASCO GI: Agent Targets IGF Receptor in Pancreatic Cancer (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18124?impressionId=1265740816432"
                     
      &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_259"
                     title="ASCO GI: Gene Therapy Shows Promise in Esophageal Cancer (CME/CE)"
                     score="0.003"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18122?impressionId=1265740816432"
                     
      &lt;p&gt;ORLANDO  --  Injecting the gene encoding for tumor necrosis factor-alpha (TNF-alpha) directly into tumors led to pathologic complete responses in a third of patients and a median survival of four years in a small study of patients with locally advanced esophageal cancer.&lt;/p&gt;
&lt;p&gt;The gene-therapy strategy led to nodal conversion and downstaging in a majority of patients, most of whom underwent surgical resection following chemoradiation and the intratumoral injections of TNF.&lt;/p&gt;
&lt;p&gt;Patients who received the three lowest doses of TNF in the dose-finding study had a five-year median survival of 56%.&lt;/p&gt;
&lt;p&gt;&quot;This represents an encouraging increase in survival relative to historical controls,&quot; Kenneth J. Chang, MD, of the University of California Irvine, reported here at the Gastrointestinal Cancers Symposium. &quot;These results warrant further evaluation.&quot;&lt;/p&gt;
&lt;p&gt;However, another investigator in the multicenter study cautioned that the trial was stopped because of treatment-related deaths that have not been fully explained, and that the regimen is complicated and time-consuming.&lt;/p&gt;
&lt;p&gt;The primary objective of the study was to assess the safety, feasibility, and tolerability of weekly intratumoral injections of TNFerade, a second-generation replication-deficient adenovector, carrying the transgene encoding human TNF-alpha, regulated by the radiation-inducible promotor Egr-1.&lt;/p&gt;
&lt;p&gt;Upon its release inside a tumor, the gene therapy stimulates TNF production to help destroy the tumor. The therapy was developed for use with radiation and conventional chemotherapy.&lt;/p&gt;
&lt;p&gt;The gene therapy has received FDA fast-track status for evaluation as treatment for pancreatic cancer.&lt;/p&gt;
&lt;p&gt;Chang reported results from a dose-finding study involving 24 patients with locally advanced esophageal cancer. All were surgical candidates before enrollment. Each patient received five weekly injections of TNF concurrent with 5-FU, cisplatin, and external-beam radiation therapy. The TNF doses evaluated ranged from 4 x 10&lt;sup&gt;8&lt;/sup&gt; to 4 x 10&lt;sup&gt;11&lt;/sup&gt; PU.&lt;/p&gt;
&lt;p&gt;Staging results showed that all but one of the patients had T3 disease, and 18 had nodal involvement (N1).&lt;/p&gt;
&lt;p&gt;The preoperative therapy was administered over 5.5 weeks. Following a recovery period of five to 11 weeks, patients were to undergo surgical resection, which ultimately was performed in 19 of the 24 study participants.&lt;/p&gt;
&lt;p&gt;Of the 19 patients who underwent resection, six (32%) had pathologic complete responses. Chang reported that nine of 16 evaluable patients converted from N1 to N0 status following preoperative therapy, and 11 of 20 were downstaged from T3 to T2-T0.&lt;/p&gt;
&lt;p&gt;Median overall survival for the patients was 47.7 months. The 56% five-year survival applied to patients in the first three dosing levels. Patients who received the highest dose have not been followed long enough to determine five-year survival.&lt;/p&gt;
&lt;p&gt;During the discussion that followed the presentation, Jaffer Ajani, MD, of M.D. Anderson Cancer Center in Houston, cited concerns about the treatment-related deaths and complexity of the regimen.&lt;/p&gt;
&lt;p&gt;&quot;This is a very big production; it&apos;s not simple to do,&quot; said Ajani. &quot;You have to have a gastroenterologist available to inject every week.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Your numbers are very small, and the pathological CR rate is no different than any other reported in even larger trials,&quot; he added. &quot;And then the subgroups with survival, I&apos;m not sure how meaningful that is because your numbers are so small.&quot;&lt;/p&gt;
&lt;p&gt;Responding to the concern about treatment-related deaths, Chang said none of the deaths was related to the TNF injections.&lt;/p&gt;
&lt;p&gt;With regard to the survival data, he acknowledged the small size of the study and said, &quot;It is what it is.&quot;&lt;/p&gt;
&lt;p&gt;&quot;It appears, as an adjunct, to be safe, and given the preliminary data, I think it is encouraging enough to go on to a larger trial,&quot; said Chang. &quot;That is basically what we are saying. We have something interesting that warrants further study.&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 GenVec.&lt;/p&gt;&lt;p&gt;One or more investigators disclosed relationships with GenVec.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_257"
                     title="ASCO GI: Targeted Agent Slows Neuroendocrine Tumors"
                     score="0.002"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18116?impressionId=1265740816432"
                     
      &lt;p&gt;ORLANDO  --  Patients with progressive pancreatic neuroendocrine tumors lived twice as long without progression when treated with sunitinib (Sutent) compared with placebo, data from a French clinical trial showed.&lt;/p&gt;
&lt;p&gt;Median overall survival had not been reached in the sunitinib arm, but sunitinib treatment was associated with a 60% reduction in hazard ratio compared with placebo. More than 90% of patients in the sunitinib group remained alive at six months, Eric Raymond, MD, reported here at the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;&quot;Sunitinib continuous daily dosing resulted in clinically significant improvement in the median progression-free survival (PFS), improvement in overall survival, and a clinically significant increase in overall response rate versus placebo,&quot; said Raymond, of Hopital Beaujon in Clichy, France.&lt;/p&gt;
&lt;p&gt;Most of the survival benefit owed to disease stabilization, as fewer than 10% of patients had objective responses.&lt;/p&gt;
&lt;p&gt;The finding suggests that sunitinib might facilitate use of second- and third-line therapies that could build on the delayed progression and extended survival, he added.&lt;/p&gt;
&lt;p&gt;Moreover, these findings appear to confirm results of phase I-II studies that showed sunitinib activity in pancreatic neuroendocrine tumors. In an open-label phase II study, for example, treatment with sunitinib led to partial responses in 16.7% of patients and stable disease &amp;#8805;6 months in 56.1%, and median time to progression of 7.7 months in 66 patients, Raymond said.&lt;/p&gt;
&lt;p&gt;Those favorable early benefits led to this multicenter phase III trial involving 170 patients, who received sunitinib 37.5 mg/d or placebo. Treatment continued until progression, death, withdrawal, and development of unacceptable toxicity. All patients also received best supportive care.&lt;/p&gt;
&lt;p&gt;The primary endpoint was progression-free survival. Secondary endpoints included overall survival, overall response rate, time to response, duration of response, safety, and patient-reported outcomes.&lt;/p&gt;
&lt;p&gt;The patients&apos; median age was 56, and 48% were men. All but one patient had ECOG 0-1 performance status. About half of the tumors were non-functioning. Among functioning tumors, gastrinomas accounted for 11%, other/multiple neuropeptide for about 8%, and unspecified for 22%.&lt;/p&gt;
&lt;p&gt;The median progression-free survival was 11.4 months in the sunitinib group and 5.5 months with placebo (HR 0.418, &lt;em&gt;P&lt;/em&gt;=0.0001). Patients treated with sunitinib had a 71.3% probability of being alive and free of disease at six months compared with 43.2% of the placebo group.&lt;/p&gt;
&lt;p&gt;Overall survival had not been reached after a median follow-up of 10 to 11 months. The probability of being alive at six months was 92.6% in the sunitinib arm and 85.2% in the placebo group. Kaplan-Meier analysis revealed a significant advantage in favor of the sunitinib arm (HR 0.409, &lt;em&gt;P&lt;/em&gt;=0.0204).&lt;/p&gt;
&lt;p&gt;Sunitinib was associated with an overall response rate of 9.3%, consisting of two complete responses and six partial responses. Additionally, 62.8% of patients in the sunitinib group had stable disease. The median response duration was 8.1 months. No objective responses occurred in the placebo group, but 60% had stable disease.&lt;/p&gt;
&lt;p&gt;Adverse events occurred more often in the sunitinib group, but grade 3+ events were uncommon in both groups.&lt;/p&gt;
&lt;p&gt;Although no unexpected adverse events were observed, Raymond said patients should be advised of the potential for graying of the hair, which occurred in almost 30% of sunitinib-treated patients.&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 Pfizer.&lt;/p&gt;&lt;p&gt;One or more investigators disclosed relationships with Pfizer.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_254"
                     title="ASCO GI: Survival Benefit with No New QoL Costs in Gastric Cancer"
                     score="0.001"
                     href="http://www.medpagetoday.com/MeetingCoverage/ASCOGI/tb/18115?impressionId=1265740816432"
                     
      &lt;p&gt;ORLANDO  --  Patients with advanced HER2-positive gastric cancer live longer, with no decline in quality of life, when trastuzumab (Herceptin) is added to chemotherapy, researchers reported here.&lt;/p&gt;
&lt;p&gt;Symptoms improved when the monoclonal antibody was added to therapy, and pain scores and use of analgesics did not differ between patients who received chemotherapy with or without trastuzumab.&lt;/p&gt;
&lt;p&gt;&quot;Trastuzumab plus chemotherapy improves overall survival and progression-free survival versus chemotherapy alone, without compromising quality of life,&quot; Taroh Satoh, MD, of Kinki University in Osaka, Japan, told attendees at the Gastrointestinal Cancers Symposium.&lt;/p&gt;
&lt;p&gt;&quot;Because the regimen is associated with prolonged progression-free survival (PFS), more patients in the trastuzumab-chemotherapy arm could benefit from improved quality of life compared to chemotherapy alone,&quot; he added.&lt;/p&gt;
&lt;p&gt;After Satoh&apos;s presentation, an invited discussant said the trastuzumab-chemotherapy regimen should be considered standard of care for patients with HER2-positive gastric cancer.&lt;/p&gt;
&lt;p&gt;The findings came from a secondary analysis of a phase III, randomized global clinical trial evaluating the safety and efficacy of trastuzumab in patients with advanced HER2-positive cancer of the stomach or gastroesophageal junction.&lt;/p&gt;
&lt;p&gt;As previously reported, the primary outcome of the study was overall survival, which improved from 11.1 months with chemotherapy to 13.8 months (&lt;em&gt;P&lt;/em&gt;=0.0046) when trastuzumab was added to chemotherapy (ASCO 2009. Abstract 4509). PFS also favored the trastuzumab arm (6.7 months versus 5.5 months, &lt;em&gt;P&lt;/em&gt;=0.0012).&lt;/p&gt;
&lt;p&gt;An exploratory analysis of patients with more intense overexpression of HER2 showed an even greater survival benefit in favor of the trastuzumab arm (16.0 months versus 11.8 months, HR 0.65, 95% CI 0.51-0.83).&lt;/p&gt;
&lt;p&gt;The study involved 584 patients, who were randomized to capecitabine (Xeloda) plus 5-FU with or without trastuzumab. Quality of life was a prespecified secondary endpoint.&lt;/p&gt;
&lt;p&gt;Satoh said quality of life, pain, and analgesic use were evaluated at baseline and then every three weeks until disease progression.&lt;/p&gt;
&lt;p&gt;Investigators used a standardized questionnaire to evaluate patients&apos; global health status, functional status, and symptoms. A questionnaire specific to gastric cancer was used to assess disease- and treatment-related symptoms, side effects, dysphagia, nutrition, and emotional status.&lt;/p&gt;
&lt;p&gt;Patients rated pain intensity by means of a visual analog scale.&lt;/p&gt;
&lt;p&gt;Compliance with both regimens remained at 95% or higher throughout most of the trial for patients who continued treatment. Global health and physical functioning scores improved in both groups, and symptom scores decreased, including nausea and vomiting, and did not differ between groups, said Satoh.&lt;/p&gt;
&lt;p&gt;Dysphagia also improved over time in both groups. Pain intensity varied somewhat but generally declined in both groups, and the magnitude of improvement was similar in both groups.&lt;/p&gt;
&lt;p&gt;The vast majority of patients maintained or decreased analgesic use over the course of the study. Satoh said 20% of the trastuzumab group and 17% of the chemotherapy arm required dose increases or the addition of a new medication.&lt;/p&gt;
&lt;p&gt;The similarity of quality-of-life outcomes reinforced most gastric cancer specialists&apos; view that trastuzumab provides a survival benefit without a negative impact on quality of life, David Cunningham, MD, of the Royal Marsden Hospital in London, said in a discussion of the study.&lt;/p&gt;
&lt;p&gt;&quot;For patients with advanced gastroesophageal cancer who are HER2-positive the combination of trastuzumab, cisplatin and a fluoropyramidine should become the new standard treatment,&quot; Cunningham said. &quot;For HER2-negative patients, we continue to search for improvement in outcome. Doublet or triplet chemotherapy would appear to be acceptable treatment options for these patients.&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;One or more investigators disclosed relationships with Roche.&lt;/p&gt;&lt;p&gt;Cunningham reported no disclossures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>