Integrierter Studienbericht

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1 Integrierter Studienbericht Studientitel Studienmedikation Indikation Sponsor Lebensqualität unter oraler Chemotherapie mit Capecitabin (Xeloda ) bei metastasiertem Brustkrebs Xeloda (Capecitabin) Therapie des metastasierten Mammakarzinoms bei HER2- negativen oder positiven Patientinnen Roche Pharma AG Grenzach-Wyhlen Studiennummer ML Studienphase NIS (nichtinterventionelle Studie) Studiendaten Einschluss der ersten Patientin: Letzte Dokumentation: Wissenschaftliche Leitung Medizinische Leitung Sponsor CRO-Projektkoordination Autoren Medical Writing Dr.med.M.Zaiss Praxis für interdisziplinäre Onkologie & Hämatologie Breisacher Str Freiburg (federführend) Dr. Stefanie Henken Medical Manager Herceptin BC RochePharmaAG Grenzach-Wyhlen Dr. Martin Indorf Clinical Trial Leader iomedico AG Freiburg Kirsten Hauswald PD Dr. med. Jens Hasskarl Dr. Martin Indorf Melanie Franzem iomedico AG Freiburg Dr. Rainer Gottwald Otto-Baab-Str Marnheim Dr.med.S.Fuxius Kurfürstenanlage Heidelberg (nicht federführend) Die in dem vorliegenden Dokument enthaltenen Informationen sind vertraulich und das Eigentum der Roche Pharma AG. Sie dürfen nicht ohne vorherige schriftliche Zustimmung der Roche Pharma AG genutzt oder offengelegt werden

2 1 Unterschriften Die in diesem Bericht behandelte Studie wurde gemäß den Empfehlungen des Bundesinstituts für Arzneimittel und Medizinprodukte und des Paul-Ehrlich-Instituts zur Planung, Durchführung und Auswertung von Anwendungsbeobachtungen und des Verbands der forschenden Arzneimittelhersteller (VfA) durchgeführt. Entsprechend der gesetzlichen Vorgaben werden die Studiendaten 10 Jahre archiviert. des Berichtes: Ich habe den vorliegenden Studienbericht gelesen und bestätige mit meiner Unterschrift, dass er die Studiendurchführung und die Darstellung der Studienergebnisse adäquat wiedergibt. Vertraulich Seite 2 von 112

3 2 Synopsis AIMS No.: ML Title: Version and Date: Draft, Sponsor: Objectives: Selected patient population: Number of patients: Selected physician population: Non-interventional post marketing surveillance study (NIS) on Quality of Life of Capecitabine (Xeloda ) in patients with metastatic breast cancer. Roche Pharma AG, Grenzach Whylen The objective of this NIS according to 67 Abs 6 AMG was the documentation of data concerning the quality of life (qol) of metastatic breast cancer patients treated with Capecitabine (Xeloda ) in mono- or combination chemotherapy of HER2- negative or positive metastatic breast cancer. In addition, information on physician s decision making efficacy of treatment and qol-influencing factors like compliance, individual treatment information level and treatment satisfaction was to be collected. The purpose of this investigation was to document the quality of life under Capecitabine (Xeloda ) treatment as a part of the daily routine treatment in Germany. The implementation of this NIS did not influence the physician s decision regarding diagnostics, therapy of frequency of medical examination during and after the treatment. HER2-negative or positive patients with metastatic breast cancer Planned: 750 Patients Actual: 756 patients registered of whom 754 started documentation and 735 received at least one dose of Capecitabine (Xeloda ) Oncologists and gynecologists in clinics, outpatient clinics and office-based physicians specialized in oncology. Internet access at site was obligatory. The sites were selected by the gynecooncology sales force of Roche Pharma AG Number of centers: Planned: 200 Actual: 161 who included patients Selection criteria: Inclusion criteria: Written and signed informed consent prior to onset of documentation Pre- or postmenopausal female patients with first-line or Vertraulich Seite 3 von 112

4 Main parameters of interest: further line locally advanced recurrent or metastatic breast cancer which are eligible for a mono-/polychemotherapy with Capecitabine (Xeloda ) by physician s decision. Exclusion criteria: Contraindications for Capecitabine (Xeloda ) according to SmPC The following questions were of particular importance: The overall and domain-related quality of life Compliance with Capecitabine (Xeloda ) treatment Patient satisfaction with Capecitabine (Xeloda )therapy Physicians satisfaction with Capecitabine (Xeloda )therapy Knowledge and satisfaction of patients with their patientphysicians communication and care Which criteria determine the therapy choice for Capecitabine (Xeloda ) Handling of hand-foot-syndrome (hfs) if this event occurs Response and time-based efficacy parameters of mono- or combination Capecitabine (Xeloda ) chemotherapy Demographic characteristics and medical history of the patient Study medication: Capecitabine (Xeloda ) was prescribed and provided from commercial stock in each study centre. Recommended dosing according to the Fachinformation (summary of product characteristics): Mono and combination therapy: 1250 mg/m² twice a day for a duration of 14 days, followed by a therapy break of 7 days Statistical considerations: Descriptive statistics or frequency counts for all variables as appropriate. Differences in QoL-scales between monotherapy and combination therapy were analyzed using mean differences with respective confidence intervals. To analyze effects on progression free survival a cox proportional regression model was used. Combination drug, therapy line and occurance of hand-foot-syndrome where included covariates. UAWs were summarized and displayed after MedDRA coding. Three descriptive interim data analyses were performed in addition Vertraulich Seite 4 von 112

5 to the final statistical analysis. Duration: First patient in: Aug 2008 Last patient in: Oct 2011 Treatment duration per patient: up to 9 months Follow-up period: none Summary of Effectiveness Results: QoL: Global score 53%. No correlation of QoL and hand-foot syndrome. Response: ORR 35,1%, DCR 64,4%. Best Response: CR 4,2%, PR 30,9%, SD 29,3%, PD 23,0%, Progression-free survival: PFS (median) 6,81 months (95% CI 6,32-7,63); PFS (with HFS): 8,4 months (95%-CI 7,5-9,2; p<0,0001) Summary of Safety Results: Incidence of Serious Adverse Reactions: 6,8% Incidence of hand-foot syndrome (all grades): 27,1%. Safety and tolerability are assessed as acceptable Conclusion: No negative impact of hand-foot syndrome on global QoL. Hand-foot syndrome predictive factor with regard to prolonged PFS. Favourable risk-benefit relation. Vertraulich Seite 5 von 112