Bondarenko, Igor N.

Di Leo, Angelo

Garnett, Sally

Jerusalem, Guy

Khasanov, Rustem

Lichinitser, Mikhail R.

Lindemann, Justin P.O.

Martin, Miguel

Pedrini, José L.

Pendergrass, Kelly

Petruzelka, Lubos

Smirnova, Iya

Torres, Roberto

Verhoeven, Didier

Repository for DZ &quot;DMA&quot;

Abstracts / The Breast 20 (2011) S12–S55 S45underlying incidence (from year 0) was calculated. Late-stage breastcancers were defined as pT2-4.Results: In year 1, the incidence ratio of late-stage breast cancers was 1.11(95% CI 1.00-1.22). After decreasing to values next to unity in years 2 and3, the ratio showed a weakly significant reduction in years 4 (0.91; 0.81-1.01) and 5 (0.88; 0.79-0.99). A significant and stable reduction wasobserved in years 6 (0.79; 0.70-0.90), 7 (0.77; 0.67-0.89), and 8 (0.79;0.67-0.93).Discussion: Starting from the 6th year of screening, the incidence of late-stage breast cancers decreased by slightly more than 20%. This observationpredicts a mortality reduction and is consistent with the results of otherevaluations from the same programmes.PO98SURVIVAL OF WOMEN DIAGNOSED WITH COMPRESSION SYNDROMEDUE TO BONE METASTASIS SECONDARY TO BREAST CANCERAnke Bergmann 1,2, Luiz Claudio Thuler 1,3, Erica Alves NogueiraFabro 1, Elisangela Ribeiro Pedrosa 1, Ana Carolina PadulaRibeiro 1, Blenda do Amaral e Silva 1, Marcelo Bello 11 Instituto Nacional de Câncer / MS, Rio de Janeiro/RJ, Brazil2Centro Universitário Augusto Motta, Rio de Janeiro/RJ, Brazil3Universidade Federal do Estado do Rio de Janeiro/UNIRIO, Rio de Janeiro/RJ,BrazilIntroduction: 60% of breast cancer cases are diagnosed in advanced stagesin Brazil. Metastases occur more often on bone structures, and axialskeleton is the most common. As a consequence, these women candevelop radicular and/or spinal cord compression syndrome, highlightedby neurological changes below the spinal cord damage level, reflectingimportant functional loss.Objective: To describe survival as well as clinical and demographic profileof women diagnosed with spinal cord compression syndrome followingbreast cancer.Material and Methods: Study on survival of women diagnosed withcompression syndrome at the Hospital of Cancer III from the BrazilianNational Cancer Institute (INCA), between May 2006 and April 2007.Outcome was considered when death occurred and cases that did notevolve to compression syndrome until April 2010 were refused. Variablesrelated to demographic and clinical features were collected. Descriptiveanalysis was carried out through measures of central and dispersiontendencies for continuous variables and absolute and relative frequenciesfor dichotomous variables. Survival analysis was carried out by the Kaplan-Meier method. The study was approved by INCA's Research and EthicsCommittee.Results: 36 cases were diagnosed with compression syndrome, 50% ofwhich were spinal cord, 30% radicular and 20% both spinal cord andradicular. Average age at breast cancer diagnosis was 53 years old (DP 13.8)and 81% with staging equal to or higher than IIIA. Concomitantly to boneimplant, metastasis was observed in the liver (28%), lungs (14%) and centralnervous system (8.3%). Spinal cord compression occurred in the dorsalregion (72%), cervical region (16%) and lumbar region (12%). Radicularcompression was more likely to occur in the second (29%) and fifth (29%)lumbar vertebras. Median time between cancer diagnosis and bonemetastasis was 17 months (0-167) and 30 months (0-167) until compres-sion syndrome. Among palliative treatments, all underwent radiotherapy,61% underwent chemotherapy, and 75%, bisphosphonates. The womenwere followed up after compression syndrome, inmedian, for 8months (0-47). Death occurred in 92% of cases, in median, after 2 months (1-99) frombone metastasis diagnosis and nine months (0-47) after compressionsyndrome diagnosis.Conclusion: Thewomen studiedwere young and diagnosedwith advancedbreast cancer. Median time between cancer diagnosis and bone metastasiswas 17 months and 30 months before compression syndrome. The womenwere followed up after compression syndrome, in median, for 8 months,and death occurred in 92% of cases. Survival was 22 months after bonemetastasis diagnosis and nine months after radicular or spinal cordcompression syndrome diagnosis.PO99APPLICATION OF NEW METHODOLOGY TO ALLOW COMPARISON OFDURATION OF RESPONSE AND DURATION OF CLINICAL BENEFITBETWEEN FULVESTRANT TREATMENT GROUPS IN THE CONFIRM TRIALSally Garnett 1, Miguel Martin 2, Guy Jerusalem3, LubosPetruzelka 4, Roberto Torres 5, Igor N. Bondarenko 6, RustemKhasanov 7, Didier Verhoeven 8, José L. Pedrini 9, Iya Smirnova 10, MikhailR. Lichinitser 11, Kelly Pendergrass 12, Justin P.O. Lindemann 1, Angelo DiLeo 131AstraZeneca, Macclesfield, UK2Hospital Universitario Gregorio Maranon, Madrid, Spain3Centre Hospitalier Universitaire Sart Tilman, Liège, Belgium4 First Faculty of Medicine of Charles University, Prague, Czech Republic5 Instituto Nacional del Cáncer, Santiago, Chile6Dnipropetrovsk Municipal Clinical Hospital, Dnipropetrovsk, Ukraine7Republican Clinical Oncological Center, Kazan, Russia8AZ. Klina, Brasschaat, Belgium9Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil10Medical Radiological Science Center, Obninsk, Russia11Russian Cancer Research Centre, Moscow, Russia12Kansas City Cancer Center, Kansas City, USA13Hospital of Prato, Prato, ItalyBackground: Duration of response (DoR) and duration of clinical benefit(DoCB) are widely evaluated during randomised oncology trials and areimportant clinical measures that help to determine a drug's therapeuticvalue. These values are calculated using a subset of responding patientsdefined post-randomisation. As a result, the subset of patients whorespond in a control arm may not be comparable with the subset in anexperimental treatment arm in terms of important prognostic factors.Consequently, such comparisons may be prone to biases and may notreflect actual treatment effects. Attempts have been made to overcomethese challenges and, using the methodology described by Ellis andcolleagues (Ellis et al. Contemp Clin Trials 2008; 29(4): 456-465), wepresent a prospective analysis of DoR and DoCB between two fulvestrant(an oestrogen receptor antagonist indicated for the second-line treatmentof postmenopausal women with endocrine-sensitive advanced breastcancer) treatment groups (500mg vs 250mg) from the double-blind, PhaseIII, COmparisoN of Faslodex In Recurrent or Metastatic breast cancer(CONFIRM) trial.Methods: For each fulvestrant dose group, the objective response rate(ORR) was calculated out of all randomised patients with measurabledisease at baseline while clinical benefit response rate (CBR) was calcu-lated across all randomised patients. The resultant ORR and CBR were usedto calculate the expected DoR (EDoR) and expected DoCB (EDoCB) for eachfulvestrant dose group from randomisation to progression or death (fromany cause). The ratios for EDoR and EDoCB (EDoR500/EDoR250 andEDoCB500/EDoCB250) were then calculated.Results: The ORRs for fulvestrant 500mg and 250mg were 13.8% (33/240) and 14.6% (38/261), respectively (odds ratio: 0.94; 95% confidenceinterval [CI] 0.57-1.55, p¼0.795). The EDoRs for fulvestrant 500mg and250mg were 3.19 and 3.57 months, respectively. The ratio of EDoRbetween fulvestrant 500mg and 250mg was not statistically significant(0.89; 95% CI 0.48-1.67, p¼0.724). The CBRs for fulvestrant 500mg and250mg were 45.6% (165/362) and 39.6% (148/374), respectively (oddsratio: 1.28; 95% CI 0.95-1.71, p¼0.100). The EDoCBs for fulvestrant500mg and 250mg were 9.83 and 7.24 months, respectively. TheEDoCB for fulvestrant 500mg was significantly improved comparedwith the EDoCB for fulvestrant 250mg (1.36; 95% CI 1.07-1.73,p¼0.013).Conclusion: Our analysis of EDoR and EDoCB showed that treatment withfulvestrant 500mg resulted in a statistically significant increase in EDoCBcompared with fulvestrant 250mg in the CONFIRM trial. As far as we areaware, this is the first study of endocrine therapy in breast cancer toformally compare DoR and DoCB by prospectively applying the method-ology of Ellis et al. This methodology provides an additional efficacyendpoint option for clinical studies where stabilisation of disease isa clinically relevant endpoint.

Application of new methodology to allow comparison of duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial

http://repo.dma.dp.ua/6394/1/1-s2.0-S0960977611002657-main.pdf

Application of new methodology to allow comparison of duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial

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Application of new methodology to allow comparison of duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial

Abstract

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Repository for DZ &quot;DMA&quot;

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