qanastek/EMEA-V3 huggingface dataset:
A positive opinion was adopted by consensus on 20 September 2007.
Ġiet adottata opinjoni pożittiva permezz ta ’ kunsens fl- 20 ta ’ Settembru 2007.
The list of the product names concerned is given in Annex I.
Il- lista ta ’ ismijiet tal- prodotti hija mogħtija fl- Anness I.
The scientific conclusions are provided in Annex II, together with the Summary of Product Characteristics in Annex III.
Il- konklużjonijiet xjentifiċi huma pprovduti fl - Anness II, flimkien mas- Sommarju tal- Karatteristiċi tal- Prodott fl- Anness III.
The final opinion was converted into a Decision by the European Commission on 22 November 2007.
L- opinjoni finali ġiet konvertita f’ Deċiżjoni mill- Kummissjoni Ewropea fit- 22 ta ’ Novembru 2007.
COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP)
IL- KUMITAT GĦALL- PRODOTTI MEDIĊINALI GĦALL- UŻU MILL- BNIEDEM (CHMP)
SUMMARY INFORMATION ON REFERRAL OPINION PURSUANT TO ARTICLE 31 OF COUNCIL DIRECTIVE 2001/ 83/ EC, AS AMENDED, FOR
TAGĦRIF FIL- QOSOR DWAR L- OPINJONI TA 'RIFERIMENT SKOND L- ARTIKOLU 31 TAD- DIRETTIVA TAL- KUNSILL 2001/ 83/ KE, KIF EMENDATA GĦAL
Bicalutamide 150 mg-containing medicinal products (See Annex 1)
Prodotti mediċinali li fihom Bicalutamide 150 mg (Ara l- Anness 1)
International Non-Proprietary Name (INN): bicalutamide
Isem Internazzjonali Mhux Patentat (INN): bicalutamide
BACKGROUND INFORMATION
TAGĦRIF TA 'SFOND
Bicalutamide is an oral anti-androgen used in the management of prostate cancer.
Bicalutamide hu anti- androġenu orali użat fil- ġestjoni tal- kanċer tal- prostata.
Bicalutamide 150 mg is marketed in the EU following national and Mutual Recognition application procedures.
Bicalutamide 150 mg tqiegħed fis- suq fl- UE wara proċeduri ta 'applikazzjoni nazzjonali u ta' Rikonoxximent Reċiproku.
It is also approved in Norway and Iceland.
Hu approvat ukoll fin- Norveġja u fl- Iżlanda.
Its authorised indications include the treatment of patients with locally advanced prostate cancer, as an immediate therapy either alone or as adjuvant to treatment by radical prostatectomy or radiotherapy.
L- indikazzjonijiet awtorizzati tiegħu jinkludu t- trattament ta 'pazjenti b' kanċer tal- prostata avvanzat lokalment, bħala terapija immedjata jew waħdu jew bħala għajnuna għat- trattament bit- tneħħija radikali tal- prostata jew bir- radjuterapija.
Locally advanced prostate cancer refers to larger tumours or tumours with spread to lymph nodes, but not involving spread to other organs.
Kanċer tal- prostata lokalment avvanzat jirreferi għal tumuri kbar jew tumuri li jkunu nfirxu għan- noduli limfatiċi, iżda li ma jkunux infirxu għal organi oħra.
On 27 July 2006, Belgium presented a referral to the EMEA under Article 31 of Directive 2001/ 83, as amended.
Fis- 27 ta 'Lulju 2006, il- Belġju ppreżenta riferiment lill- EMEA skond l- Artikolu 31 tad- Direttiva 2001/ 83, kif emendata.
The reasons for referral concerned a review of the benefit/ risk profile of medicinal products containing bicalutamide 150 mg.
Ir- raġunijiet għar- riferiment kellhom x' jaqsmu ma 'analiżi tal- profil tal - benefiċċju/ riskju ta' prodotti mediċinali li fihom bicalutamide 150 mg.
The 4 issues raised in the referral concerned the analyses of the Early Prostate Cancer Programme (EPC):
L- erba 'kwistjonijiet imqajma b' rabta ma' l- analiżi tal- Programm tal- Kanċer tal- Prostata Bikri (EPC):
- the lack of an overall survival benefit versus adverse events in ‘ locally advanced prostate cancer’;
- in- nuqqas ta 'benefiċċju globali ta' sopravivenza meta mqabbel ma 'l- avvenimenti avversi fil -' kanċer tal -
- statistical concerns regarding multiplicity;
- tħassib statistiku dwar il- multiċipliċità;
- the standard of care for the placebo group in the relevant studies;
- l- istandard tal- kura tal- grupp tal- plaċebo fl- istudji relevanti;
- the number of deaths due to cardiac failure.
- l- għadd ta 'mwiet minħabba indeboliment kardijaku.
The referral procedure started on 27 July 2006.
Il- proċedura ta 'riferiment bdiet fis- 27 ta' Lulju ta 'l- 2006.
The Rapporteur and Co-Rapporteur appointed were Dr Julia Dunne and Dr Ingemar Persson, respectively.
Ir- Rapporteur u l- Ko- Rapporteur maħtura kienu Dr Julia Dunne u Dr Ingemar Persson, rispettivament.
Written explanations were provided by the Marketing Authorisation Holders on 20 October 2006, 22 March 2007 and on 15 May 2007.
Ingħataw tifsiriet bil- miktub lid- Detentur ta 'l - Awtorizzazzjoni għat- Tqegħid fis- Suq fl- 20 ta' Ottubru 2006, fit- 22 ta 'Marzu 2007 u fil- 15 ta' Mejju ta 'l - 2007.
Oral explanations were given on 22 May 2007.
Ingħataw tifsiriet orali fit- 22 ta 'Mejju 2007.
Based on evaluation of the available data and the Rapporteurs’ assessment reports, the CHMP considered that the benefit/ risk profile of bicalutamide 150 mg-containing medicinal products remains favourable, and therefore adopted an opinion on 24 May 2007 recommending the maintenance or the granting, as appropriate, of the Marketing Authorisations with amendments to the relevant sections of the Summary of Product Characteristics, for bicalutamide 150 mg-containing medicinal products.
Skond l- evalwazzjoni tad- dejta disponibbli u tar- rapporti ta 'valutazzjoni tar- Rapporteurs, is- CHMP ikkonsidra li l- profil tal- benefiċċju/ riskju ta' mediċini li fihom bicalutamide 150 mg jibqa 'wieħed favorevoli, u għalhekk adotta opinjoni fl- 24 ta' Mejju ta 'l- 2007 li tirrakkomanda ż- żamma jew l- għoti, kif inhu xieraq, ta' l- Awtorizzazzjonijiet tat- Tqegħid fis- Suq bl- emendi għat- taqsimiet relevanti tas - Sommarju tal- Karatteristiċi tal- Prodott għal prodotti mediċinali li fihom bicalutamide 150 mg.
The CHMP considered that bicalutamide 150 mg is effective in the treatment of locally advanced prostate cancer; however the CHMP considered that the therapeutic indication should be restricted to treatment of patients at high risk of disease progression.
Is- CHMP ikkonsidra li bicalutamide 150 mg hu effettiv fit- trattament tal- kankru tal- prostata avvanzat lokalment; madankollu s- CHMP ikkonsidra li l- indikazzjoni terapewtika għandha tkun ristetta għat - trattament ta 'pazjenti b' riskju għoli ta' progress tal- marda.
In view of the available data, the CHMP concluded that a potential association between the use of bicalutamide 150 mg and heart failure cannot be ruled out and therefore considered that the need to further study cardiovascular morbidity and mortality remains.
Fid- dawl tad- dejta disponibbli, is- CHMP ikkonkluda li ma tistax tkun eskluża assoċjazzjoni potenzjali bejn bicalutamide 150 mg u l- falliment tal- qalb u għalhekk ikkonsidra l- ħtieġa ta 'iktar studju dwar il - mortalità u l- morbidità kardjovaskulari għadha teżisti.
To address this concern, a new epidemiological study will be performed, as part of an agreed Risk Management Plan.
Biex jiġi indirizzat dan it- tħassib, se jsir studju epidemjoloġiku ġdid, bħala parti mill- Pjan ta 'Ġestjoni tar- Riskju maqbul.
(44-20) 74 18 84 00 Fax (44-20) 74 18 86 68 E-mail: mail@emea. eu. int http: / /www. emea. eu. int ©. EMEA 2006 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged * Note:
(44- 20) 74 18 86 00 Fax (44- 20) 74 18 84 68 E- mail: mail@ emea. eu. int http: // www. emea. eu. int ©. EMEA 2006 Reproduction and/ or distribution of this document is authorised for non commercial purposes only provided the EMEA is acknowledged Il- lista ta 'ismijiet tal- prodotti konċernati qed tingħata fl- Anness I.
The information given in this document and Annexes reflect only the CHMP Opinion dated 24 May 2007.
L- opinjoni finali ġiet konvertita f' Deċiżjoni mill- Kummissjoni Ewropea fil- 03. 09. 2007.
The Member States’ competent authorities will continue to keep the product under regular review.
It- tagħrif mogħti f' dan id- dokument u fl- Annessi jirriflettu biss l- Opinjoni tas- CHMP bid- data ta 'l- 24 ta' Mejju ta 'l- 2007 / L- awtoritajiet kompetenti ta' l- Istati Membri se jkomplu għaddejjin b' analiżi regolari tal- prodott.
16 August, 2007
27 ta 'Awwissu 2007
LIST OF THE NAMES, PHARMACEUTICAL FORM, STRENGTH OF THE MEDICINAL PRODUCTS, ROUTE OF ADMINISTRATION, APPLICANTS, MARKETING AUTHORISATION HOLDERS IN THE MEMBER STATES
LISTA TAL- ISMIJIET, GĦAMLA FARMAĊEWTIKA, QAWWA TAL- PRODOTTI FARMAĊEWTIĊI, ROTTA MINN FEJN JINGĦATA, APPLIKANTI, DETENTURI TA ’ L - AWTORIZZAZZJONI GĦAT- TQEGĦID FIS- SUQ FL- ISTATI MEMBRI
1 Marketing Authorisation Holders
1 Detentur ta ’ l- awtorizzazzjoni għat- tqegħid fis- suq
Marketing Authorisation Holder
Detentur ta ’ l- awtorizzazzjoni għat - tqegħid fis- suq
Route of administration
Rotta minn fejn jingħata
AT - Austria
AT - L - Awstrija
film-coated tablet
Pillola miksija b’ rita Użu orali
BE - Belgium
BE - Il – Belġju
BG - Bulgaria
BG - Il - Bulgarija
CS - Czech Republic
CS - Ir - Repubblika Ċeka
CS - Czech Republic
CS - Ir - Repubblika
617 00 Brno CY - Cyprus
617 00 Brno Ċeka CY - Ċipru
DA - Denmark
DA - Id - Danimarka
EL - Greece
EL - Il - Greċja
ET - Estonia
ET - L - Estonja
FI - Finland
FI - Il - Finlandja
3 Member State
3 Stat Membru
FI - Finland
FI - Il -
oral use
Finlandja
4 Member State
4 Stat Membru
20 Queen Frederiks Street, Office 301 1066 Nicosia, Cyprus FI - Finland
20 Queen Frederiks Street, Office 301 1066 Nicosia, Cyprus FI - Il - Finlandja
5 Member State
5 Stat Membru
20097 Hamburg, Germany FI - Finland
20097 Hamburg, Germany FI - Il - Finlandja
HU - Hungary
HU - L - Ungerija
6 Member State
6 Stat Membru
H-2045 IS - Iceland
H- 2045 IS – L- Islanda
IT - Italy
IT – L - Italja
LT - Lithuania
LT – Il - Litwanja
LU - Luxembourg
LU – Il -
oral use
Lussemburgu 110 rue E.
LV - Latvia
Van Ophem B- 1180 Bruxelles Belgium LV – Il – Latvja
oral use
NO – In - Norveġja
oral use
PL – Il -
7 Member State
7 Stat Membru
Silk Road Business Park Macclesfield Cheshire SK10 2NA United Kingdom PT - Portugal
Silk Road Business Park Polonja Macclesfield Cheshire SK10 2NA United Kingdom PT – Il - Portugall
PT - Portugal
PT – Il - Portugall
RO-Romania
RO – Ir - Rumanija
SK – Slovakia
SK – Is - Slovakkja
SL - Slovenia
SL – Is -
8 Member State
8 Stat Membru
15 Stanhope Gate London, W1K 1LN United Kingdom SV - Sweden
15 Stanhope Gate Slovenja London, W1K 1LN United Kingdom SV – L - Isvezja
UK - United Kingdom
UK – Ir - Renju Unit
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS PRESENTED BY THE EMEA
KONKLUŻJONIJIET XJENTIFIĊI U RAĠUNIJIET GĦALL- EMENDI TAS- SOMMARJU TAL - KARATTERISTIĊI TAL- PRODOTT IPPREŻENTATI MILL- EMEA
10 SCIENTIFIC CONCLUSIONS
10 KONKLUŻJONIJIET XJENTIFIĊI
OVERALL SUMMARY OF THE SCIENTIFIC EVALUATION OF BICALUTAMIDE 150 mg CONTAINING MEDICINAL PRODUCTS (see Annex I)
SOMMARJU GLOBALI TA ’ L- EVALWAZZJONI XJENTIFIKA TA ’ PRODOTTI MEDIĊINA LI FIHOM BICALUTAMIDE 150 mg (ara Anness I)
Background
Sfond
Bicalutamide is an oral anti-androgen used in the management of prostate cancer.
Bicalutamide hu prodott anti- androġeniku orali użat fil- ġestjoni tal- kanċer tal- prostata.
Bicalutamide 150 mg is marketed in the EU following national and Mutual Recognition application procedures.
Bicalutamide 150 mg iddaħħal fis- suq fl- UE wara proċeduri ta ’ l- applikazzjoni tar- Rikonoxximent nazzjonali u Reċiproku.
Its authorised indications include the treatment of patients with locally advanced prostate cancer, as an immediate therapy either alone or as adjuvant to treatment by radical prostatectomy or radiotherapy.
L - awtorizzazzjonijiet indikati jinkludu t- trattament ta ’ pazjenti b’ kanċer tal- prostata lokalment avvanzat, bħala terapija immedjata, waħdu jew flimkien ma ’ trattament bit- tneħħija radikali tal- prostata jew bir- radjuterapija.
Locally advanced prostate cancer refers to larger tumours or tumours with spread to lymph nodes, but not involving spread to other organs.
Kanċer tal- prostata lokalment avvanzat jirreferi għal tumuri ikbar jew tumuri mifruxa fin- nodi limfatiċi, iżda li ma jinkludux firxa lejn organi oħra.
In 2004, 2 publications were published detailing a pre-planned 2nd analysis of the Casodex (bicalutamide) Early Prostate Cancer (EPC) study programme.
Fl- 2004 kienu ppubblikati żewġ pubblikazzjonijiet b’ dettalji dwar it- tieni analiżi tal- programm ta ’ studju ta ’ Casodex (bicalutamide) Early Prostate Cancer (EPC).
These same data were considered by the UK, the Reference Member State (RMS) for the Mutual Recognition Procedure (MRP), in 2003.
Dan l- istess tagħrif ġie ikkunsidrata mir- Renju Unit, l- Istat Membru ta ’ Referenza (RMS) għall- Proċedura tar - Rikonoxximent Reċiproku (MRP), fl- 2003.
At that time, the RMS concluded that Casodex (bicalutamide) 150 mg should not be used in the treatment of ‘ localised’ prostate cancer, however, it was concluded that the benefit/ risk balance remained positive for selected patients in ‘ locally advanced’ prostate cancer, as immediate therapy either alone or as adjuvant to treatment by radical prostatectomy or radiotherapy.
Fl- istess żmien, l- RMS ikkonkluda li Casodex (bicalutamide) 150 mg m’ għandux jintuża fit- trattament ta ’ kanċer tal- prostata ‘ lokalizzat ’, madankollu, ġie konkluż li l- bilanċ bejn ir- riskju u l- benefiċċju baqa ’ pożittiv għal pazjenti magħżula fil- kanċer tal- prostata ‘ lokalment avvanzat ’, bħala terapija immedjata jew waħdu jew bħala żieda mat- trattament bit- tneħħija radikali tal- prostata jew bir - radjuterapija.
Section 5.1 of the SPC was amended to note that the optimum medical strategy for a patient at low risk of disease progression, particularly in the adjuvant setting following radical prostatectomy, might be to defer hormonal therapy until signs that the disease is progressing.
It- Taqsima 5. 1 ta ’ l- SPC ġiet emendata biex tinnota li l- istrateġija medika ottima għal pazjent b’ riskju baxx ta ’ progressjoni tal- marda, partikolarment bħala żieda mat- trattament wara t- tneħħija radikali tal - prostata, tista ’ tkun dik li tipposponi it- terapija ormonali sakemm ikun hemm sinjali li l- marda tkun qed tipprogressa.
Following their own review of these data carried out in 2004 and due to their resulting concerns over the benefit/ risk balance of bicalutamide 150 mg in locally advanced prostate cancer, the Belgian Regulatory Authority suspended their national Marketing Authorisation for Casodex (bicalutamide) 150 mg in August 2005.
Wara l- analiżi tagħhom ta ’ dan it- tagħrif li wettqu fl- 2004 u minħabba l- preokkupazzjonijiet li konsegwentement irriżultaw minn naħa tagħhom dwar il- bilanċ bejn il- benefiċċju u r- riskju ta ’ bicalutamide 150 mg fil- kanċer tal- prostata lokalment avvanzat, l- Awtorità Regolatorja Belġjana ssospendiet l - Awtorizzazzjoni għat- Tqegħid fis- Suq għal Casodex (bicalutamide) 150 mg f’ Awwissu 2005.
In view of the concerns related to safety and efficacy for bicalutamide 150 mg the National Competent Authority (NCA) in Belgium considered it to be in the interest of public health to perform a new benefit/ risk assessment.
Fl- isfond tat- tħassib dwar is- sigurtà u l- effikaċja għal bicalutamide 150 mg l- Awtorità Kompenti Nazzjonali (NCA) fil- Belġju qieset li kien fl- interess għas saħħa pubblika li ssir valutazzjoni mill - ġdid tal- benefiċċju u r- riskju.
Therefore, Belgium referred the issue on 27 July 2006 for consideration by CHMP under Article 31 of Directive 2001/ 83/ EC, as amended.
Għalhekk, fis- 27 ta ’ Lulju il- Belġju rrefera l- kwistjoni għall- konsiderazzjoni mis- CHMP skond l - Artiklu 31 tad- Direttiva 2001/ 83/ KE, kif emendata.
The 4 issues raised in the referral concern the analyses of the Early Prostate Cancer Programme (EPC):
L- erba ’ kwistjonijiet imressqa għar- referenza jikkonċernaw l- analiżi tal- programm Early Prostate Cancer (EPC)
- the lack of an overall survival benefit versus adverse events in ‘ locally advanced prostate cancer’;
- in- nuqqas ta ’ benefiċċju globali fis- sopravivenza kontra l- avvenimenti mhux mixtieqa fil - ‘ kanċer tal -
- statistical concerns regarding multiplicity;
- tħassib statistiku dwar il- multipliċità;
- the number of deaths due to cardiac failure.
- l- għadd ta ’ mwiet minħabba kollass tal- qalb.
Based on the concerns raised, the following questions were posed to the Applicants/ MAHs as part of the consolidated CHMP List of Questions, the responses to which were the basis of the CHMP reassessment of the benefit/ risk balance:
Minħabba t- tħassib li tqajjem, tressqu dawn il- mistoqsijiet lill- Applikanti/ Deteneturi ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq bħala parti mil- Lista konsolidata ta ’ Mistoqsijiet mis- CHMP, li t- tweġibiet għalihom kienu l- bażi tal- valutazzjoni mill- ġdid tal- bilanċ bejn il- benefiċċju u r- riskju mis- CHMP:
1/ How does the company justify the indication of bicalutamide 150 mg for locally advanced prostate cancer knowing the absence of statistically significant overall survival and the important side effects?
1 / Il- kumpanija kif tiġġustifika l- indikazzjoni ta ’ bicalutamide 150 mg għall- kanċer tal- prostata lokalment avvanzat meta taf li m’ hemmx sopravivenza globali statistikament sinifikanti u hemm effetti mhux mixtieqa importanti?
2/ How does the company justify the absence of adjustment for tests of multiplicity in the analysis of the EPC results?
2 / Il- kumpanija kif tiġġustifika n- nuqqas ta ’ aġġustament għat- testijiet tal- multipliċità fl- analiżi tar - riżultati ta ’ l- EPC?
3/ How does the company justify that the placebo arm did not receive an adequate treatment according to the present standard of care and why this is not taken into account in the analysis of the EPC results?
3 / Il- kumpanija kif tiġġustifika l- fatt li l- grupp li ngħata l- plaċebo ma ngħatax trattament xieraq skond l - istandards attwali tal- kura u l- fatt li dan ma ġiex ikkunsidrat fl- analiżi tar- riżultati ta ’ l- EPC?
4/ How can the company rule out any role of bicalutamide 150 mg in the increased mortality due to heart failure in the Casodex arm of the EPC trial?
Il- kumpanija kif tista ’ teskludi li bicalutamide 150 mg seta ’ kellu x’ jaqsam maż- żieda fil- mortalità minħabba kollass tal- qalb fil- grupp li kien qed jingħata Casodex fl- istudju EPC?
Further, the referral concerned only
L- iskop tar- referenza kien jinkludi wkoll l- applikazzjonijiet kollha għal Awtorizzazzjonijiet għat- Tqegħid fis- Suq li huma pendenti kif ukoll l- Awtorizzazzjonijiet għat- Tqegħid fis- Suq kollha ta ’ prodotti mediċinali li fihom bicalutamide 150mg.
11 the locally advanced prostate cancer indication based on the Early Prostate Cancer study programme, and the directly related wording in sections 4.1 and 5.1 of the SPC.
Ir- referenza kienet tikkonċerna biss l- indikazzjoni tal- kanċer tal- prostata lokalment avvanzat ibbażata fuq il- programm ta ’ studju Early Prostate Cancer (EPC) u l- kliem direttament relatat li hemm fit- taqsima 4. 1 u 5. 1 tal - SPC.
Other aspects of the SPC and the other indication for bicalutamide 150 mg, which is approved in some EU member states, were not within the scope of the referral.
Aspetti oħra tal - SPC kif ukoll l- indikazzjoni l- oħra għal bicalutamide 150mg, li hija approvata f’ xi stati membri tal – EU, ma kinux fl- iskop ta ’ din ir- referenza.
Benefit/ Risk considerations
Kunsiderazzjonijiet tal- Benefiċċju/ Riskju
When the EPC programme was initiated more than 8 years ago, the aim was to document the benefit of early bicalutamide therapy versus placebo as monotherapy or adjuvant therapy to surgery or radiotherapy.
Meta nbeda l- programm ta ’ l- EPC iktar minn tmien snin ilu, l- għan kien li jiġi dokumentat il- benefiċċju ta ’ terapija bikrija b ’ bicalutamide mqabbla ma ’ plaċebo bħala t- terapija ewlenija jew bħala terapija miżjuda mal- kirurġija jew mar- radjuterapija.
The lack of broad consensus in the standard of care for early prostate cancer makes it difficult to study.
In- nuqqas ta ’ qbil vast dwar l- istandard ta ’ kura għall- kanċer bikri tal - prostata joħloq diffikultajiet f’ dan l- istudju.
The EPC study was an empirical design, that is to say, it generally compared Casodex (bicalutamide) to the standard of care in each region involved.
L- istudju ta ’ l- EPC kien disinn empiriku, fi kliem ieħor, huwa qabbel b’ mod ġenerali lill- Casodex (bicalutamide) ma ’ l- istandard tal- kura f’ kull reġjun in kwistjoni.
It is acknowledged that overall there is no statistically significant survival benefit in locally advanced prostate cancer.
Hu magħruf li m’ hemmx benefiċċju fis- sopravivenza statistikament sinjifikanti fil- kanċer tal- prostata lokalment avvanzat.
However, the EPC study was positive for the primary progression free survival (PFS) endpoint, both overall and in the locally advanced subgroups.
Madankollu, l- istudju kien pożittiv għall - indikatur primarju tas- sopravivenza mingħajr progressjoni, kemm globalment kif ukoll fil- gruppi avvanzati lokalment.
At the initial authorisation of the early prostate cancer indication, the data for overall survival were too immature to allow an analysis, however it makes sense to subsequently analyse this endpoint in the same subgroups, and there are favourable trends in overall survival for patients with locally advanced disease receiving Casodex (bicalutamide) alone, and for patients also receiving radiotherapy.
Fl- awtorizzazzjoni inizjali ta ’ l- indikazzjoni bikrija tal- kanċer tal- prostata, it- tagħrif għas- sopravivenza globali kien immatur wisq biex seta ’ jippermetti li ssir analiżi, madankollu jagħmel sens li sussegwentament jiġi analizzat dan l- indikatur fl- istess sottogruppi, u hemm tendenzi favorevoli fis- sopravivenza globali tal - pazjenti b’ mard lokalment avvanzat li kienu qed jirċievu Casodex (bicalutamide) waħdu, u għall- pazjenti li kienu qed jirċievu wkoll ir- radjuterapija.
As regards the multiplicity issue raised, it is considered appropriate to look at subgroups from a statistical viewpoint, as they have helped to narrow the indication to patients with a more favourable benefit/ risk balance for bicalutamide 150 mg.
Dwar il- kwistjoni tal- multipliċità li tqajmet, hu meqjus xieraq li wieħed iħares lejn is- sottogruppi minn perspettiva statistika, għax dawn għenu fit- tnaqqis ta ’ l- indikazzjoni għal pazjenti b’ bilanċ favorevoli fil - benefiċċju/ riskju għal bicalutamide 150 mg.
These are also not arbitrary subgroups, but are implicit in the proposed indication, correspond to the way prostate cancer is classified, managed and studied, and the results are consistent with what might be expected.
Barra minn hekk, dawn m’ humiex sottogruppi arbitrarji iżda huma impliċiti fl- indikazzjoni proposta, jikkorrispondu għall- mod li hu klassifikat, ġestit u studjat il- kanċer tal- prostata, u r- riżultati huma konsistenti ma ’ dak li seta ’ kien mistenni.
It seems intuitive that for good prognosis patients who have also received treatment of curative intent, the addition of bicalutamide might confer less benefit than in other patients.
Jidher li għal pazjenti bi pronjożi tajba li kienu rċevew ukoll trattament b’ intenzjoni ta ’ fejqan, iż- żieda ta ’ bicalutamide tista ’ twassal għal inqas benefiċċji milli f’ pazjenti oħra.
In addition, the survival advantage observed in patients with locally advanced disease receiving radiotherapy appears to be consistent with that seen in previous studies, and a synergistic effect with radiotherapy is plausible.
Barra minn hekk, il- vantaġġ fis- sopravivenza osservata fil- pazjenti b’ mardiet lokalment avvanzati li kienu qed jingħataw ir- radjuterapija jidher li hu konsistenti ma ’ dak li deher fl- istudji ta ’ qabel, u effett sinerġistiku mar- radjuterapija hu plawsibbli.
It is difficult to obtain overall survival data in patients with early prostate cancer due to its insidious course.
Hu diffiċli li jinkiseb tagħrif fuq is - sopravivenza globali fil- pazjenti bil- kanċer tal- prostata bikri minħabba r- rotta insidjuża tiegħu.
For these reasons, the CHMP considers that the progression-free survival results are important and can be considered on their merits.
Minħabba dawn ir- raġunijiet, is- CHMP jikkunsidra li r- riżultati tas- sopravivenza mingħajr progressjoni huma importanti u jistgħu jiġu kkunsidrati fuq il- merti tagħhom.
Disease progression may be associated with problems such as painful bone metastases, cord compression, pathological fractures and urinary obstruction.
Il- progressjoni tal- marda tista ’ tiġi assoċjata ma ’ problemi bħall- metastasi bl- uġigħ fil- għadam, kompressjoni tal- korda, ksur patoloġiku u ostakoli urinarju.
The PFS results are given again below:
Ir - riżultati tal- PFS qed jingħataw hawn taħt:
Progression-free survival in locally advanced disease by therapy sub-group
Sopravivenza mingħajr progressjoni f’ mard lokalment avvanzat, skond is- sotto grupp tat- terapija
Analysis population
Popolazzjoni Studjata
Events (%) in Casodex patients
Avvenimenti (%) fil -
Events (%) in placebo patients
Avvenimenti (%) fil -
Watchful waiting Radiotherapy Radical prostatectomy
Stennija bl- attenzjoni Radjuterapija Tneħħija radikali tal -
193/ 335 (57.6) 66/ 161 (41.0) 179/ 870 (20.6)
193/ 335 (57. 6) 66/ 161 (41. 0)
222/ 322 (68.9) 86/ 144 (59.7) 213/ 849 (25.1)
222/ 322 (68. 9) 86/ 144 (59. 7)
0.60 (0.49 to 0.73) 0.56 (0.40 to 0.78) 0.75 (0.61 to 0.91)
prostata
In particular, there is a statistically significant and clinically meaningful improvement in progression-free survival in the patients with locally advanced prostate cancer who received Casodex (bicalutamide) as compared to placebo (58% versus 69% progressors in patients who were not receiving adjuvant surgery or radiotherapy).
12 B’ mod partikolari, hemm titjib statistikament sinjifikanti u klinikament relevanti fis- sopravivenza mingħajr progressjoni fil- pazjeni b’ kanċer tal- prostata lokalment avvanzat li kienu ħadu Casodex (bicalutamide) meta mqabbla ma ’ dawk li ħadu l- plaċebo (58% u 69% f’ pazjenti li ma kinux qed jiġu ttrattati bir- radjuterapija jew bil- kirurġija).
Benefit is generally a function of risk progression and in patients with locally advanced disease; benefit is reduced after surgery or in cases where radiotherapy is likely to be curative.
Il- benfiċċju hu ġeneralment funzjoni tal- progressjoni tar- riskju u fil- pazjenti b’ mardiet lokalment avvanzati, l- benefiċċju jitnaqqas wara l- kirurġija jew f’ każijiet fejn ir- radjuterapija jkollha probabilità qawwija li twassal għall- fejqan.
With reference to the adequacy of treatment in the placebo group in the EPC studies, given that at the time of initiation of these studies there was no widely agreed standard of care in locally advanced prostate cancer (something which remains the case), the empirical design of the studies, which compared Casodex (bicalutamide) 150mg or placebo when given as an adjunct to “ standard care” is considered reasonable.
B’ referenza għall- adegwatezza tat- trattament fil- grupp tal- plaċebo fl- istudji EPC, billi fi żmien il- bidu ta ’ dawn l- istudji, ma kienx hemm qbil dwar l- istandard tal- kura fil- kanċer tal- prostata lokalment avvanzat (kif għadu sal- lum), id- disinn empiriku ta ’ dawn l- istudji, li qabblu Casodex (bicalutamide) 150mg jew il- plaċebo meta mogħti bħala żieda mal - “ kura standard ” hu meqjus raġonevoli.
12 None of the EPC trials mandated that treatment be withheld from patients in the placebo group until clinical progression.
L- ebda studju EPC ma rrakkomanda li t- trattament jitwaqqaf lil pazjenti fil- grupp tal- plaċebo sakemm ikun hemm progress kliniku.
The median PSA levels on initiation of active therapy for each subgroup are above the thresholds in current European Association of Urology (EAU) guidance.
Il- livelli medjani tal- PSA fil- bidu tat- terapija attiva għal kull wieħed mis- sottogruppi huma ’ l fuq mil- livelli msemmija fil- gwidi attwali ta ’ l- Assoċjazzjoni Ewropea ta ’ l- Uroloġija (EAU).
These results should of course be balanced against the well-known tolerability issues of Casodex (bicalutamide).
Naturalment, dawn ir- riżultati għandhom jiġu bbilanċjati mal- kwistjonijiet magħrufa ħafna tat- tolerabilità ta ’ Casodex (bicalutamide).
Gynaecomastia and breast pain have been highlighted (mainly in the 1st year of intake) and can be managed in many patients.
Il- kobor tas- sider u l- uġigħ fis- sider intwerew (prinċipalment fl- ewwel sena ta ’ l - istudju) u jistgħu jiġu ġestiti f’ ħafna pazjenti.
In the clinical studies this was severe in around 5% of patients.
Fl- istudji kliniċi, dan kien sever f’ madwar 5% tal- pazjenti.
Gynaecomastia may not resolve spontaneously following cessation of therapy, particularly after prolonged treatment.
Il - kobor tas- sider jista ’ ma jirrisolvix ruħu waħdu wara t- twaqqif tat- trattament, partikolarment jekk it - trattament kien għal- tul mhux ħażin ta ’ żmien.
EAU guidelines suggest the use of prophylactic breast radiation, tamoxifen or aromatase inhibitors to manage these symptoms, although they are not licensed in this use.
Il- linji gwida ta ’ l- EAU jissuġġerixxu l- użu profilattiku tar - radjazzjoni tas- sider, tamoxifen jew l- inibituri ta ’ aromatose biex jiġu ġestiti dawn is- sintomi, għalkemm ma ngħatawx liċenzja għal dan l- użu.
The requested additional analyses of the EPC trial data confirm an increased risk for deaths coded as heart failures (however, with no overall excess risk in the cardiovascular system), an increased risk of urogenital symptoms (including gynaecomastia and breast pain) mainly during the first year of intake, and further indicate the absence of an adverse effect on thromboembolic events during the follow-up (supported by a pattern of events inconsistent with hormonal effects).
L- analiżi addizzjonali mitluba għat- tagħrif dwar l- istudju ta ’ l- EPC tikkonferma żieda ikbar fir- riskju għall - mewt ikkodifikata bħala kollass tal- qalb (madankollu, bl- ebda riskju globali żejjed fis- sistema kardjovaskulari), żieda fir- riskju ta ’ sintomi uroġenitali (inkluż il- kobor tas- sider u l- uġigħ fis- sider) prinċipalment matul l- ewwel sena tad- dħul ta ’ pazjenti fl- istudju, u jindikaw ukoll in- nuqqas ta ’ effetti mhux mixtieqa fl- avvenimenti tromboembolitiċi matul is- sorveljanza tal- pazjent (appoġġjata minn sensiela ta ’ avveniment mhux konsistenti ma ’ l- effetti ormonali).
There was no evidence of an overall excess mortality.
Ma kienx hemm evidenza ta ’ żieda fil- mortalità globali.
With reference to heart failure mortality, the MAHs have submitted a limited amount of new data since this issue was last assessed, namely results from a further clinical study, an updated literature review and an updated review of their safety database.
B’ referenza għall- mortalità mill- kollass tal- qalb, id- Deteneturi ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq issottomettew ammont limitat ta ’ tagħrif ġdid minn meta ġiet valutata l- aħħar il- kwistjoni, jiġifieri r- riżultati ta ’ studju kliniku ieħor, analiżi riċenti tal- pubblikazzjonijiet u analiżi rivedutata tad- database tas- sigurtà.
The numbers involved are relatively small, there is no consistent pattern for heart failure deaths over the longer term, and there is some unreliability in selecting this as a cause of death.
In - numri involuti huma relattivament baxxi, m’ humiex konsistenti għal perjodu twil ta ’ żmien u xi drabi m’ humiex ta ’ min joqgħod fuqhom fl- għażla tal- kawża tal- mewt.
However, an association with bicalutamide cannot be ruled out.
Madankollu, ma tistax tiġi eskluża assoċjazzjoni ma ’ bicalutamide.
Whilst the pattern of adverse events argues against a role for raised oestrogen levels, it is known that the myocardium has androgen receptors, and it might be affected by long-term androgen deprivation.
Waqt li t- tendenza ta ’ l- effetti mhux mixtieqa ssaħħaħ l- argument kontra sehem għal livelli elevati ta ’ estroġenu, hu magħruf li l- muskolu tal- qalb li għandu riċetturi għall- androġenu, jista ’ jiġi affettwat minn nuqqas fit- tul ta ’ l- androġenu.
However, the numbers of cases involved are relatively small, and there is no clear temporal relationship.
Madankollu, l- għadd ta ’ każijiet involuti hu relattivament baxx, u m’ hemmx relazzjoni temporali ċara.
The majority of patients with heart failure had confounding factors at study entry, and the causality assessment of investigators for all deaths ascribed to heart failure was “ not related”.
Il- biċċa l- kbira tal- pazjenti b’ kollass tal- qalb kellhom fatturi konfondenti waqt id- dħul fl- istudju, u l - valutazzjoni tal- każwalità ta ’ l- investigaturi għall- imwiet kollha attribwiti għall- kollass tal- qalb “ ma kinitx relatata ”.
Regarding the heart failure deaths, the allocation of cause of death is known to be unreliable, and very few post-mortems were done.
Dwar l- imwiet mill- kollass tal- qalb, l- allokazzjoni tal- kawża tal- mewt hi meqjusa mhux ta ’ min joqgħod fuqha, u saru biss ftit awtopsji.
Due to a small number of relevant subjects, no conclusions could be drawn regarding the contribution of tamoxifen or radiotherapy to cardiovascular outcomes, or on whether tamoxifen exposure had a synergistic effect on efficacy.
Minħabba n- numru żgħir ta ’ suġġetti relevanti, wieħed ma jista ’ jasal għall- ebda konklużjoni dwar il- kontribut ta ’ tamoxifen jew tar- radjuterapija għar- riżultati kardjovaskulari, jew għal jekk il- preżenza ta ’ tamoxifen kellhiex effett sinerġetiku fuq l- effikaċja.
However, it is not possible to entirely “ rule out” thromboembolic events as contributory explanation of increased cardiovascular mortality.
Madankollu, ma kienx possibbli li jkunu esklużi kompletament xi avvenimenti tromboembolitiċi bħala spjegazzjoni kontributorja għaż- żieda fil- mortalità kardjovaskulari.
The need to further study cardiovascular morbidity and mortality remains.
Għad hemm il- ħtieġa għal iktar studju dwar il- mortalità u l- morbidità kardjovaskulari.
A new pharmacoepidemiological study will be undertaken as part of an agreed Risk Management Plan (RMP), a post-opinion commitment to get a better understanding of cardiovascular risk.
Sa jsir studju farmakoepidemoloġiku ġdid bħala parti minn Pjan għall- Ġestjoni tar- Riskju (RMP) li sar qbil dwaru, bil - għan li jkun hemm għarfien aħjar dwar ir- riskju kardjovaskulari.
The aim of the study is to estimate the incidence of heart failure, cardiovascular morbidity and mortality in patients with prostate cancer, compared to the general population.
L- għan ta ’ l- istudju kien li ssir stima ta ’ l - inċidenza tal- kollass tal- qalb, il- morbidità u l- mortalità kardjovaskulari fil- pazjenti bil- kanċer tal- prostata
Further, the study will include prostate cancer subgroups to include those on Casodex (bicalutamide), and those treated with luteinizing hormone-releasing hormone (LHRH) analogues, orchidectomy, and other hormonal therapies.
Barra minn hekk, l- istudju sa jinkludi sotto gruppi ta ’ pazjenti bil - kanċer biex jinkludi dawk li qed jieħdu Casodex (bicalutamide), u dawk ittrattati b’ analogi ta ’ l- LHRH, bit - tneħħija tat- testikoli, u b’ terapiji ormonali oħra.
The 4th analysis of the EPC data will also be provided when available.
Ir- raba ’ analiżi tad- dejta ta ’ l- EPC se tkun mogħtija wkoll meta din tkun disponibbli.
In conclusion, the heart failure data remain a concern and are inconclusive, but do not significantly alter the benefit/ risk balance in locally advanced prostate cancer patients.
Fl- aħħar nett, it- tagħrif dwar il- kollass tal- qalb jibqa ’ ta ’ tħassib u huwa inkonklussiv, iżda ma jbiddilx b’ mod sinjifikanti l- bilanċ bejn il- benefiċċju u r- riskju f’ pazjent b’ kanċer tal- prostata lokalment avvanzat.
However, these data do support the Committee’ s position that the indication should be restricted to selected patients with locally advanced prostate cancer at high risk of disease progression.
Madankollu, dan it- tagħrif jappoġġja l- pożizzjoni tal- Kumitat li l- indikazzjoni għandha tkun ristretta għal pazjenti magħżula b’ kanċer tal- prostata lokalment avvanzat b’ riskju għoli ta ’ progressjoni tal- marda.
How such patients are identified could be based on criteria such as PSA levels, Gleason score and stage of disease.
L- identifikazzjoni ta ’ dawn il- pazjenti tista ’ tkun ibbażata fuq il- kriterji bħal- livelli tal- PSA, Gleason score u l- istadju tal- marda.
A more specific target population is hard to define from the EPC data, and the general term “ high risk” better accommodates wide differences in local practice and inevitable changes in the standard of care, and takes into account the many variables in the individual patient which may contribute to risk of progression.
Hu diffiċli li tiġi definita popolazzjoni fil- mira iktar speċifika mit- tagħrif ta ’ l- EPC, u t - terminu ġenerali “ riskju għoli ” jakkomoda aħjar id- differenzi kbar bejn il- prattika lokali u l- bidliet inevitabbli fl- istandard tal- kura, u jikkonsidra l- ħafna fatturi varjabbli fil- pazjent individwali li jistgħu jikkontribwixxu għar- riskju ta ’ progressjoni.
The SPC has been amended accordingly and notes in section 5.1 that, for patients with locally advanced disease “ A reduction in risk of objective disease progression… was most evident in those at highest risk of disease progression.
Il- pazjenti u l- professjonisti kliniċi għandhom jiddeċiedu liema hu l- iktar trattament xieraq fuq bażi individwali, wara li jkunu ddiskutew l- aspetti ta ’ l- effikaċja u t - tollerabilità ta ’ kull trattament disponibbli, ir- riskji kollha magħrufa għall- progressjoni tal- marda, u wara konsiderazzjoni ta ’ l- istil tal- ħajja tal- pazjent.
Therefore, clinicians may
L- SPC ġie emendat kif xieraq u f’ Taqsima 5. 1 jinnota li, għal pazjenti b’ marda lokalment avvanzata “ tnaqqis fir- riskju tal- progressjoni oġġettiva tal- marda… kien l- iktar evidenti f’ dawk il- pazjenti bl- ogħla riskju ta ’ progressjoni tal- marda.
13 decide that the optimum medical strategy for a patient at low risk of disease progression, particularly in the adjuvant setting following radical prostatectomy, may be to defer hormonal therapy until signs that the disease is progressing .” Section 5.1 of the SPC also includes a summary of the efficacy results from the EPC study.
Għalhekk, il- professjonisti kliniċi jistgħu jiddeċiedu li l- aqwa strateġija medika għal pazjent b’ riskju baxx ta ’ progressjoni tal- marda, partikolarment fil- kuntest tas- sorveljanza tat- tneħħija radikali tal- prostata, jista ’ jwassal għal posponiment tat- terapija ormonali sakemm ikun hemm sinjali li l- marda tkun qed tagħmel progress. ” Sezzjoni 5. 1 ta ’ l - SPC tinkludi wkoll sommarju tar- riżultati ta ’ l- effikaċja mill- istudju ta ’ l- EPC.
GROUNDS FOR AMENDMENT OF THE SUMMARY OF PRODUCT CHARACTERISTICS
RAĠUNIJIET GĦALL- EMENDI TAS- SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT
-
- Il- Kumitat ikkunsidra r- referenza magħmula skond l- artiklu 31 tad- Direttiva 2001/ 83/ KE, kif
The Committee considered the referral made under article 31 of Directive 2001/ 83/ EC, as amended, for medicinal products containing bicalutamide 150 mg.
emendata, għall- prodotti mediċinali li fihom bicalutamide 150 mg.
The Committee considered that bicalutamide 150 mg is effective in the treatment of locally advanced prostate cancer; however the CHMP considered that the therapeutic indication should be restricted to treatment of patients at high risk of disease progression.
- Il- Kumitat ikkunsidra li bicalutamide 150 mg hu effettiv fit- trattament tal- kanċer tal- prostata
-
- Fl- isfond tat- tagħrif disponibbli, is- CHMP ikkonkluda li l- assoċjazzjoni potenzjali bejn l- użu
In view of the available data, the CHMP concluded that a potential association between the use of bicalutamide 150 mg and heart failure cannot be ruled out and therefore considered that the need to further study cardiovascular morbidity and mortality remains.
ta ’ bicalutamide 150 mg u l- kollass tal- qalb ma tistax tiġi eskluża u allura qies li għad hemm bżonn ta ’ iktar studju dwar il- mortalità u l- morbidità kardjovaskulari.
To address this concern, a new epidemiological study will be performed, as part of an agreed Risk Management Plan.
Biex jindirizza dan it - tħassib, se jsir studju epidemoloġiku ġdid, bħala parti mill- Pjan tal- Ġestjoni tar- Riskju.
-
- Is- CHMP ikkonkluda li l- bilanċ bejn il- benefiċċji u r- riskji ta ’ prodotti mediċinali li fihom
The CHMP concluded that the benefit/ risk balance of bicalutamide 150 mg containing medicinal products in the agreed restricted indication is favourable.
bicalutamide 150 mg lifl- indikazzjonijiet ristretti li dwarhom hemm qbil, hu favorevoli.
As a consequence, the CHMP has recommended to maintain the Marketing Authorisations for all medicinal products and to grant Marketing Authorisations for all applications referred to in Annex I of the Opinion in accordance with the amendments to the relevant sections of the Summary of Product Characteristics, set out in Annex III of the Opinion.
Minħabba f’ hekk, is- CHMP irrakkomanda t- tkomplija ta ’ l- Awtorizzazzjonijiet għat- Tqegħid fis- Suq għall - prodotti mediċinali kollha u l- għoti ta ’ Awtorizzazzjonijiet għat- Tqegħid fis- Suq għall- applikazzjonijiet imsemmija fl- Anness I ta ’ l- Opinjoni skond l- emendi għat- taqsimiet relevanti tas- Sommarju tal- Karatteristiċi tal- Prodott, stabbiliti fl- Anness III ta ’ l- Opinjoni.
AMENDMENTS TO THE SUMMARY OF PRODUCT CHARACTERISTICS
EMENDI FIS - SOMMARJU TAL- KARATTERISTIĊI TAL- PRODOTT
This Annex III (Amendments to the Summary of Product Characteristics) is the one that was Annexed to the Commission Decision on this Article 31 referral for bicalutamide 150 mg containing medicinal products.
Dan l- Anness III (Emendi fis- Sommarju tal- Karatteristiċi tal- Prodott) huwa dak li kien Anness mad- Deċiżjoni tal- Kummissjoni dwar din ir- referenza għall- Artikolu 31 dwar bicalutamide 150mg li jikkonsisti fi prodotti mediċinali.
The text was valid at that time.
It- test kien validu dak iż- żmien.
After the Commission Decision, the Member State competent authorities will update Annex III as required.
Wara id- Deċiżjoni tal- Kummissjoni, l- awtoritajiet kompetenti ta ’ l- Istati Membri għandhom jaġġornaw l- Anness III kif meħtieġ.
Therefore, Annex III may not necessarily represent the current text.
4. 1 Indikazzjonijiet terapewtiċi
[Invented name] 150mg is indicated either alone or as adjuvant to radical prostatectomy or radiotherapy in patients with locally advanced prostate cancer at high risk for disease progression (see section 5.1).
[Isem ivvintat] 150mg huwa indikat kemm waħdu jew bħal għajnuna wara li titneħħa l- prostata jew radjuterapija, f’ pazjenti b’ kanċer tal- prostata lokalment avvanzat, b’ riskju għoli li tinfirex il- marda.
CASODEX (Bicalutamide) 150 mg was studied as a treatment for patients with localised (T1-T2, N0 or NX, M0) or locally advanced (T3-T4, any N, M0; T1-T2, N+, M0) non-metastatic prostate cancer in a combined analysis of 3 placebo controlled double-blind studies in 8113 patients, where CASODEX was given as immediate hormonal therapy or as adjuvant to radical prostatectomy or radiotherapy, (primarily external beam radiation).
CASODEX (bicalutamide) 150mg kien studjat bħala trattament għal pazjenti bil- kanċer tal- prostata mingħajr metastasi, lokalizzat (T1- T2, N0 jew NX, M0) jew lokalment avvanzat (T3- T4, kwalunkwe N, M0; T1- T2, N+, M0) f’ analiżi kombinata ta ’ tlett studji kontrollati double- blind bi plaċebo b’ 8113- il pazjent fejn CASODEX ingħata bħala terapija ormonali immedjata jew bħal għajnuna wara li titneħħa l- prostata jew radjuterapija (l- aktar b’ raġġ ta ’ radjazzjoni esterna).
At 7.4 years median follow up, 27.4% and 30.7% of all CASODEX and placebo-treated patients, respectively, had experienced objective disease progression.
F’ medjan ta ’ 7. 4 snin follow- up, 27. 4% u 30. 7% tal - pazjenti kollha li ġew trattati b’ CASODEX jew plaċebo, rispettivament, kellhom progressjoni oġġettiva tal - marda.
A reduction in risk of objective disease progression was seen across most patient groups but was most evident in those at highest risk of disease progression.
Tnaqqis fir- riskju tal- progressjoni oġġettiva tal- marda dehret fost bosta gruppi ta ’ pazjenti, imma kienet l - aktar evidenti f’ dawk bl- ogħla riskju ta ’ progessjoni tal- marda.
Therefore, clinicians may decide that the optimum medical strategy for a patient at low risk of disease progression, particularly in the adjuvant setting following radical prostatectomy, may be to defer hormonal therapy until signs that the disease is progressing.
Għalhekk, dawk li jmexxu l- klinika jistgħu jiddeċiedu li l- aħjar strateġija medika għal pazjent b’ riskju baxx ta ’ progessjoni tal- marda, l- aktar f’ xenarju ta ’ terapija aġġuntiva wara t- tneħħija radikali tal- prostata, hija li tiġi differita t- terapija ormonali sakemm ikun hemm sinjali ta ’ progressjoni tal- marda.
No overall survival difference was seen at 7.4 years median follow up with 22.9% mortality (HR=0.99; 95% CI 0.91 to1.09).
Ma dehret l- ebda differenza fis- sopravivenza totali f’ medjan ta ’ 7. 4 snin ta ’ follow up, bi 22. 9% mortalità (HR = 0. 99; 95% CI 0. 91 sa 1. 09).
However, some trends were apparent in exploratory subgroup analyses.
Madankollu xi tendenzi kienu evidenti f’ analiżi ta ’ sottogrupp esploratorju.
Progression-free survival and overall survival data for patients with locally advanced disease are summarised in the following tables:
Dejta għal sopravivenza mingħajr progressjoni u sopravivenza totali f’ pazjenti bil- marda lokalment avvanzata hija miġbura fil- qosor fit- tabelli li ġejjin:
Progression-free survival in locally advanced disease by therapy sub-group
Sopravivenza mingħajr progressjoni f’ marda lokalment avvanzata skond is - sottogrupp tat- terapija
Analysis population
Analiżi tal popolazzjoni
Events (%) in Events (%) in placebo Hazard ratio CASODEX patients patients (95% CI)
Każijiet (%) Każijiet (%) Proporzjon ta ’ f’ pazjenti fuq plaċebo periklu f’ pazjenti fuq (95% CI) CASODEX
193/ 335 (57.6) 222/ 322 (68.9) 0.60 (0.49 to 0.73) 66/ 161 (41.0) 86/ 144 (59.7) 0.56 (0.40 to 0.78)
Stennija bl- attenzjoni Radjuterapija Tneħħija radikali tal - prostata
179/ 870 (20.6)
193/ 335 (57. 6) 66/ 161 (41. 0) 179/ 870 (20. 6)
213/ 849 (25.1)
222/ 322 (68. 9) 86/ 144 (59. 7) 213/ 849 (25. 1)
0.75 (0.61 to 0.91)
0. 60 (0. 49 to 0. 73) 0. 56 (0. 40 to 0. 78) 0. 75 (0. 61 to 0. 91)
Table 2
16 Tabella 2
Overall survival in locally advanced disease by therapy sub-group
Sopravivenza totali f’ marda lokalment avvanzata skond is- sottogrupp tat - terapija
Deaths (%) in Deaths (%) in placebo Hazard ratio CASODEX patients patients (95% CI)
Mwiet (%) Mwiet (%) Proporzjon ta ’ periklu f’ pazjenti fuq f’ pazjenti fuq plaċebo (95% CI) CASODEX
164/ 335 (49.0) 183/ 322 (56.8) 0.81 (0.66 to 1.01) 49/ 161 (30.4) 61/ 144 (42.4) 0.65 (0.44 to 0.95)
Stennija bl- attenzjoni Radjuterapija Tneħħija radikali tal - prostata
137/ 870 (15.7)
164/ 335 (49. 0) 49/ 161 (30. 4) 137/ 870 (15. 7)
122/ 849 (14.4)
183/ 322 (56. 8) 61/ 144 (42. 4) 122/ 849 (14. 4)
1.09 (0.85 to 1.39)
0. 81 (0. 66 to 1. 01) 0. 65 (0. 44 to 0. 95) 1. 09 (0. 85 to 1. 39)
In these patients there was also a trend toward decreased survival compared with
Għal pazjenti b’ marda lokalizzata li qed jirċievu CASODEX waħdu, ma kien hemm l- ebda differenza sinifikanti fis- sopravivenza mingħajr progressjoni.
16 placebo patients (HR=1.16; 95% CI 0.99 to 1.37).
F’ dawn il- pazjenti kien hemm ukoll tendenza lejn tnaqqis fis- sopravivenza meta mqabbel ma ’ pazjenti li qed jirċievu plaċebo (HR=1. 16; 95% CI 0. 99 sa 1. 37).
In view of this, the benefit-risk profile for the use of CASODEX is not considered favourable in this group of patients.
Il - profil tal- benefiċċju kontra r- riskju għall- użu ta ’ CASODEX mhux meqjus favorevoli f’ dan il- grupp ta ’ pazjenti.
17 ANNEX IV
17 ANNESS IV
18 National Competent Authorities (NCA), coordinated by the Reference Member State (RMS), shall ensure that the following conditions are fulfilled by the Marketing Authorisation Holders:
18 L- Awtorijtajiet Nazzjonali Kompetenti (NCA), ikkoordinati mill- Istat Membru ta ’ Referenza (RMS), għandhom jiżguraw li d- Detenturi ta ’ l- Awtorizzazzjoni għat- Tqegħid fis- Suq (MAH) jissodisfaw il - kundizzjonijiet li ġejjin:
- A new pharmacoepidemiological study(ies) should be undertaken to get a better understanding of
- Għandu( hom) isir( u) studju( i) farmakoepidemoloġiku( ċi) ġdid (ġodda) biex ir- riskju kardjovaskulari
cardiovascular risk.
jinftiehem aħjar.
The aim of the study should be to estimate the incidence of heart failure, cardiovascular morbidity and mortality in patients with prostate cancer, compared to the general population.
L- għan ta ’ dan l- istudju għandu jkun l- istima ta ’ l- inċidenza tal- kollass tal- qalb, mortalità u morbidità kardjovaskulari f’ pazjenti bil- kanċer tal- prostata, meta mqabbla ma ’ dawk tal - popolazzjoni ġenerali.