Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin

SUMMARY. We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon- alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities.

SCOTROC 2A: Carboplatin followed by docetaxel or docetaxel gemcitabine as first-line chemotherapy for ovarian cancer

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P = 0.102, P = 0.056, P = 0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% Cl: 10.5 - 20.6); arm B 18.1 months (95% Cl: 15.9 - 20.3); arm C, 13.7 months (95% Cl: 12.8 - 14.6). Neutropenia was the predominant grade 3 - 4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P = 0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

Whole brain irradiation following surgery or radiosurgery for solitary brain metastases: Mature results of a prematurely closed randomized Trans-Tasman Radiation Oncology Group trial (TROG 98.05)

We evaluated the effect of adjuvant whole brain irradiation (WBI) after surgery or radiosurgery for solitary brain metastases in a Phase III multicentre trial with randomization to 30-36 Gy WBI or observation. The study was closed early due to slow accrual after 19 patients (WBI 10, observation 9). There was no difference in CNS failure-free survival or overall survival between the arms. There was a trend to reduced CNS relapse with WBI (30% versus 78%, P = 0.12). Limited analysis of quality of life and neurocognitive function data revealed no evidence of difference between the arms. Our results are not inconsistent with two larger randomized trials and support the use of upfront WBI to decrease brain recurrence in this setting. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

WOMAC 20, 50, 70 response levels in patients treated with Rofecoxib for osteoarthritis

Aim of study: The goal of this post-hoc analysis was to examine the difference between treatment groups when varying the target response level from at least a 20% improvement from baseline, to at least 50% and 70% improvements in Phase III studies of rofecoxib in patients with osteoarthritis. Methods: The analysis focused on results from two 6-week, placebo-controlled, ibuprofen-comparator, Phase III osteoarthritis studies. These studies employed a flare design requiring a minimum level of symptoms at entry following discontinuation of prior analgesics. Two definitions of ‘‘patient improved’’ from baseline were used: (1) WOMAC-P: a reduction in the WOMAC pain score and (2) WOMAC-PFS: a reduction in the WOMAC pain score and either a reduction in the WOMAC stiffness or function score. The improvement target was increased from 20% to 50% to 70%, relative to baseline, to investigate how the increase affects the ability to detect the differences between treatment groups. Analyses were conducted on the average and last of all measurements collected during a 6-week treatment period. Results: In the ibuprofen-comparator studies, 1545 patients were randomized to placebo, rofecoxib 12.5 mg once daily, rofecoxib 25 mg once daily, and ibuprofen 800 mg three times daily in a 1:3:3:3 ratio. The percentages of patients who met the improvement targets decrease as the target increases from 20% to 50% to 70%. There were meaningful differences between the active treatment and placebo that were inversely related to the improvement target. For example, there was a 31 (P ! 0.001), 21 (P ! 0.001), and 12 (P ! 0.001) percentage-point difference between rofecoxib 25 mg and placebo for the 20%, 50%, and 70% targets for WOMAC-P. For WOMAC-PFS, the differences between rofecoxib 25 mg and placebo were 33 (P ! 0.001), 18 (P ! 0.001), and 9 (P ! 0.01) percentage points for the 20%, 50%, and 70% improvement targets. Conclusions: Meaningful differences between active treatments and placebo were detected at all three response levels associated with the WOMAC-P and WOMAC-PFS endpoints. The differences between groups were more dramatic at the 20% and 50% response levels. The WOMAC (20,50,70)-P and WOMAC (20,50,70)-PFS endpoints further confirm, at an individual patient level, the clinical benefit of rofecoxib in the treatment of osteoarthritis that was previously reported as a difference in means.

ANÁLISE DA DENSIDADE ÓPTICA DA SUTURA PALATINA MEDIANA APÓS A EXPANSÃO RÁPIDA DA MAXILA ASSISTIDA CIRURGICAMENTE

A Expansão Rápida da Maxila Assistida Cirurgicamente (ERMAC) é um recurso ortodôntico-cirúrgico utilizado no tratamento das más oclusões com deficiência transversal da maxila em pacientes adultos que apresentam a consolidação da sutura palatina mediana. A proposta neste estudo foi a de avaliar as densidades ópticas da sutura palatina mediana antes da ERMAC (fase I), após o fechamento do parafuso expansor (fase II), após 3 meses do fechamento do parafuso expansor (fase III) e após 6 meses do procedimento cirúrgico. A amostra deste estudo foi constituída por 64 radiografias oclusais de 16 pacientes na faixa etária de 18 a 40 anos, sendo 6 do sexo masculino e 10 do sexo feminino que necessitavam submeter-se à Expansão Rápida da Maxila Assistida Cirurgicamente (ERMAC) e com atresia maxilar superior a 5 mm. Foram obtidas as radiografias oclusais e as imagens digitalizadas das quatro fases do estudo. Duas áreas de interesse foram demarcadas nas imagens digitalizadas, uma entre os incisivos centrais superiores e outra após o término do parafuso expansor. Procedeu-se às leituras das densidades ópticas pelo programa Image Tool for Windows por meio do Histograma. Após a análise estatística dos valores obtidos de densidade óptica das regiões analisadas pela Análise de Variâncias (ANOVA) e comparações múltiplas de Bonferroni (complemento da ANOVA), pode-se concluir que: a densidade óptica na região da sutura palatina mediana nas 4 fases estudadas, apresentou grande variação, compatível com a abertura da referida sutura e posterior neoformação óssea no período pós-operatório; foi observado valor decrescente para as densidades ópticas após o fechamento do parafuso expansor nas regiões A e B ; foi observado que após 3 meses do fechamento do parafuso expansor, as densidades ópticas aumentaram nas regiões A e B . Isso sugeriu neoformação óssea na região da sutura palatina mediana; foi observado que após 6 meses do procedimento cirúrgico, as densidades ópticas aumentaram em relação à fase anterior. Na região A , observou-se que os valores das densidades ópticas não retornaram aos valores pré-tratamento, ou seja, antes da Expansão Rápida da Maxila Assistida Cirurgicamente (ERMAC). Já os valores das densidades ópticas médias da região B retornaram aos valores iniciais, antes da ERMAC. A análise estatística revelou que após 6 meses do procedimento cirúrgico, houve diferença estatisticamente significante ao se avaliar a região A comparando as fases entre si, porém ao se avaliar a região B não houve diferença estatisticamente significante ao se comparar as fases I e IV.

GEO Label:user and producer perspectives on a label for geospatial data

One of the aims of the Science and Technology Committee (STC) of the Group on Earth Observations (GEO) was to establish a GEO Label- a label to certify geospatial datasets and their quality. As proposed, the GEO Label will be used as a value indicator for geospatial data and datasets accessible through the Global Earth Observation System of Systems (GEOSS). It is suggested that the development of such a label will significantly improve user recognition of the quality of geospatial datasets and that its use will help promote trust in datasets that carry the established GEO Label. Furthermore, the GEO Label is seen as an incentive to data providers. At the moment GEOSS contains a large amount of data and is constantly growing. Taking this into account, a GEO Label could assist in searching by providing users with visual cues of dataset quality and possibly relevance; a GEO Label could effectively stand as a decision support mechanism for dataset selection. Currently our project - GeoViQua, - together with EGIDA and ID-03 is undertaking research to define and evaluate the concept of a GEO Label. The development and evaluation process will be carried out in three phases. In phase I we have conducted an online survey (GEO Label Questionnaire) to identify the initial user and producer views on a GEO Label or its potential role. In phase II we will conduct a further study presenting some GEO Label examples that will be based on Phase I. We will elicit feedback on these examples under controlled conditions. In phase III we will create physical prototypes which will be used in a human subject study. The most successful prototypes will then be put forward as potential GEO Label options. At the moment we are in phase I, where we developed an online questionnaire to collect the initial GEO Label requirements and to identify the role that a GEO Label should serve from the user and producer standpoint. The GEO Label Questionnaire consists of generic questions to identify whether users and producers believe a GEO Label is relevant to geospatial data; whether they want a single "one-for-all" label or separate labels that will serve a particular role; the function that would be most relevant for a GEO Label to carry; and the functionality that users and producers would like to see from common rating and review systems they use. To distribute the questionnaire, relevant user and expert groups were contacted at meetings or by email. At this stage we successfully collected over 80 valid responses from geospatial data users and producers. This communication will provide a comprehensive analysis of the survey results, indicating to what extent the users surveyed in Phase I value a GEO Label, and suggesting in what directions a GEO Label may develop. Potential GEO Label examples based on the results of the survey will be presented for use in Phase II.

Consistent reduction of postprandial glucagon and insulin by lixisenatide in the GetGoal clinical trial programme

Background and aims: Glucagon-like peptide-1 (GLP-1) receptor agonists improve islet function and delay gastric emptying in subjects with type 2 diabetes mellitus. We evaluated 2-hour glucose, glucagon and insulin changes following a standardized mixed-meal tolerance test before and after 24 weeks of treatment with the once-daily prandial GLP-1 receptor agonist lixisenatide (approved for a therapeutic dose of 20 μg once daily) in six randomized, placebo-controlled studies within the lixisenatide Phase III GetGoal programme. In the studies, the mixed-meal test was conducted before and after: (1) lixisenatide treatment in patients insufficiently controlled despite diet and exercise (GetGoal-Mono), (2) lixisenatide treatment in combination with oral antidiabetic drugs (OADs) (GetGoal-M and GetGoal-S), or (3) lixisenatide treatment in combination with basal insulin ± OAD (GetGoal-Duo 1, GetGoal-L and GetGoal-L-Asia).Materials and methods: A meta-analysis was performed (lixisenatide n=1124 vs placebo n=707) combining ANCOVA least squares (LS) mean values using an inverse variance weighted analysis. Results: Lixisenatide significantly reduced 2-hour postprandial glucose from baseline (LS mean difference vs placebo: -4.9 mmol/L, p<0.0001, Figure) and glucose excursions (LS mean difference vs placebo: -4.5 mmol/L, p<0.0001). As measured in two studies, lixisenatide also reduced postprandial glucagon (LS mean difference vs placebo: -19.0 ng/L, p<0.0001) and insulin (LS mean difference vs placebo: -64.8 pmol/L, p<0.0001), although the glucagon/insulin ratio was increased (LS mean difference vs placebo: 0.15, p=0.02) compared with placebo. Conclusion: The results show that lixisenatide potently reduces the glucose excursion after meal ingestion in subjects with type 2 diabetes, in association with marked reductions in glucagon and insulin levels. It is suggested that diminished glucagon secretion and slower gastric emptying contribute to reduced hepatic glucose production and delayed glucose absorption, enabling postprandial glycaemia to be controlled with less demand on beta-cell insulin secretion. Clinical Trial Registration Number: NCT00688701; NCT00712673; NCT00713830; NCT00975286; NCT00715624; NCT00866658 Supported by: Sanofi

Horizontal genetic transfer in asexual fungi

Four aspects of horizontal genetic transfer during heterokaryon formation were examined in the asexual pathogen Fusarium oxysporum f.sp. cubense (Foc): (1) variability based on method of heterokaryon formation; (2) differences in nuclear and mitochondrial inheritance; (3) the occurrence of recombination without nuclear fusion; (4) the occurrence of horizontal genetic transfer between distantly related isolates. The use of non-pathogenic strains of Fusarium oxysporum as biocontrol agents warrants a closer examination at the reproductive life cycle of this fungus, particularly if drug resistance or pathogenicity genes can be transmitted horizontally. Experiments were divided into three phases. Phase I looked at heterokaryon formation by hyphal anastomosis and protoplast fusion. Phase II was a time course of heterokaryon formation to look at patterns of nuclear and mitochondrial inheritance. Phase III examined the genetic relatedness of the different vegetative compatibility groups using a multilocus analysis approach. Heterokaryon formation was evident within and between vegetative compatibility groups. Observation of non-parental genotypes after heterokaryon formation confirmed that, although a rare event, horizontal genetic transfer occurred during heterokaryon formation. Uniparental mitochondria inheritance was observed in heterokaryons formed either by hyphal anastomosis or protoplast fusion. Drug resistance was expressed during heterokaryon formation, even across greater genetic distances than those distances imposed by vegetative compatibility. Phylogenies inferred from different molecular markers were incongruent at a significant level, challenging the clonal origins of Foc. Mating type genes were identified in this asexual pathogen Polymorphisms were detected within a Vegetative Compatibility Group (VCG) suggesting non-clonal inheritance and/or sexual recombination in Foc. This research was funded in part by a NIH-NIGMS (National Institutes of Health-National Institute of General Medical Sciences) Grant through the MBRS (Minority Biomedical Research Support), the Department of Biological Sciences and the Tropical Biology Program at FIU. ^

The effects of self-monitoring on homework completion and accuracy rates of students with disabilities in an inclusive general education classroom

This study investigated the effects of self-monitoring on the homework completion and accuracy rates of four, fourth-grade students with disabilities in an inclusive general education classroom. A multiple baseline across subjects design was utilized to examine four dependent variables: completion of spelling homework, accuracy of spelling homework, completion of math homework, accuracy of math homework. Data were collected and analyzed during baseline, three phases of intervention, and maintenance. ^ Throughout baseline and all phases, participants followed typical classroom procedures, brought their homework to school each day and gave it to the general education teacher. During Phase I of the intervention, participants self-monitored with a daily sheet at home and on the computer at school in the morning using KidTools (Fitzgerald & Koury, 2003); a student friendly, self-monitoring program. They also participated in brief daily conferences to review their self-monitoring sheets with the investigator, their special education teacher. Phase II followed the same steps except conferencing was reduced to two days a week, which were randomly selected by the researcher and Phase III conferencing was one random day a week. Maintenance data were taken over a two-to-three week period subsequent to the end of the intervention. ^ Results of this study demonstrated self-monitoring substantially improved spelling and math homework completion and accuracy rates of students with disabilities in an inclusive, general education classroom. On average, completion and accuracy rates were highest over baseline in Phase III. Self-monitoring led to higher percentages of completion and accuracy during each phase of the intervention compared to baseline, group percentages also rose slightly during maintenance. Therefore, results suggest self-monitoring leads to short-term maintenance in spelling and math homework completion and accuracy. ^ This study adds to the existing literature by investigating the effects of self-monitoring of homework for students with disabilities included in general education classrooms. Future research should consider selecting participants with other demographic characteristics, using peers for conferencing instead of the teacher, and the use of self-monitoring with other academic subjects (e.g., science, history). Additionally, future research could investigate the effects of each of the two self-monitoring components used alone, with or without the conferencing.^

The effectiveness of explicit individualized phonemic awareness instruction by a speech -language pathologist to preschool children with phonological speech disorders

This study investigated the effects of an explicit individualized phonemic awareness intervention administered by a speech-language pathologist to 4 prekindergarten children with phonological speech sound disorders. Research has demonstrated that children with moderate-severe expressive phonological disorders are at-risk for poor literacy development because they often concurrently exhibit weaknesses in the development of phonological awareness skills (Rvachew, Ohberg, Grawburg, & Heyding, 2003).^ The research design chosen for this study was a single subject multiple probe design across subjects. After stable baseline measures, the participants received explicit instruction in each of the three phases separately and sequentially. Dependent measures included same-day tests for Phase I (Phoneme Identity), Phase II (Phoneme Blending), and Phase III (Phoneme Segmentation), and generalization and maintenance tests for all three phases.^ All 4 participants made substantial progress in all three phases. These skills were maintained during weekly and biweekly maintenance measures. Generalization measures indicated that the participants demonstrated some increases in their mean total number of correct responses in Phase II and Phase III baseline while the participants were in Phase I intervention, and more substantial increases in Phase III baseline while the participants were in Phase II intervention. Increased generalization from Phases II to III could likely be explained due to the response similarities in those two skills (Cooper, Heron, & Heward, 2007).^ Based upon the findings of this study, speech-language pathologists should evaluate phonological awareness in the children in their caseloads prior to kindergarten entry, and should allocate time during speech therapy to enhance phonological awareness and letter knowledge to support the development of both skills concurrently. Also, classroom teachers should collaborate with speech-language pathologists to identify at-risk students in their classrooms and successfully implement evidence-based phonemic awareness instruction. Future research should repeat this study including larger groups of children, children with combined speech and language delays, children of different ages, and ESOL students.^

The Effectiveness of Explicit Individualized Phonemic Awareness Instruction By a Speech-Language Pathologist to Preschool Children With Phonological Speech Disorders

This study investigated the effects of an explicit individualized phonemic awareness intervention administered by a speech-language pathologist to 4 prekindergarten children with phonological speech sound disorders. Research has demonstrated that children with moderate-severe expressive phonological disorders are at-risk for poor literacy development because they often concurrently exhibit weaknesses in the development of phonological awareness skills (Rvachew, Ohberg, Grawburg, & Heyding, 2003). The research design chosen for this study was a single subject multiple probe design across subjects. After stable baseline measures, the participants received explicit instruction in each of the three phases separately and sequentially. Dependent measures included same-day tests for Phase I (Phoneme Identity), Phase II (Phoneme Blending), and Phase III (Phoneme Segmentation), and generalization and maintenance tests for all three phases. All 4 participants made substantial progress in all three phases. These skills were maintained during weekly and biweekly maintenance measures. Generalization measures indicated that the participants demonstrated some increases in their mean total number of correct responses in Phase II and Phase III baseline while the participants were in Phase I intervention, and more substantial increases in Phase III baseline while the participants were in Phase II intervention. Increased generalization from Phases II to III could likely be explained due to the response similarities in those two skills (Cooper, Heron, & Heward, 2007). Based upon the findings of this study, speech-language pathologists should evaluate phonological awareness in the children in their caseloads prior to kindergarten entry, and should allocate time during speech therapy to enhance phonological awareness and letter knowledge to support the development of both skills concurrently. Also, classroom teachers should collaborate with speech-language pathologists to identify at-risk students in their classrooms and successfully implement evidence-based phonemic awareness instruction. Future research should repeat this study including larger groups of children, children with combined speech and language delays, children of different ages, and ESOL students

Radiation balance of the tropical ocean surface measured during Atlantic Expedition GARP 1974 (Table 1)

The net flux of all irreversible fluxes of radiation and heat crossing the ocean surface is determined for phase III of GATE at position no. 27 (WFS "Planet", FRG). The radiation fluxes have been measured directly, while the heat fluxes have been parameterized with the bulk formula however with bulk coefficients depending on stability. The heat loss of the ocean due to warming of the cooler precipitation is included for the determination of the net flux at the ocean surface. Some examples of hourly mean values of different fluxes during different weather conditions are additionally shown.

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.

PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.

RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.

CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.

Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials.

BACKGROUND: REAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluorouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. PATIENTS AND METHODS: Analysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. RESULTS: RR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. CONCLUSIONS: The RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect.