Supplementary appendix - · PDF fileCarlos Silva Hospital S. Joao Porto, Portugal 5 Pavel...

Supplementary appendixThis appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors.

Supplement to: Chi KN, Protheroe A, Rodríguez-Antolín A,et al. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol 2017; published online Jan 8. http://dx.doi.org/10.1016/S1470-2045(17)30911-7.

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Supplementary Materials for Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naïve prostate cancer: results from the phase 3 randomised study (LATITUDE) Kim N. Chi,1 Andrew Protheroe,2 Alfredo Rodriguez-Antolin,3 Gaetano Facchini,4 Henrik Suttman,5 Nobuaki Matsubara,6 Zhangqun Ye,7 Bhumsuk Keam,8 Ronaldo Damião,9 Tracy Li,10 Kelly McQuarrie,11 Bin Jia,12 Peter De Porre,13 Jason Martin,14 Mary B. Todd,10 Karim Fizazi15 1BC Cancer Agency - Vancouver Centre, Vancouver, BC, Canada; 2Oxford University Hospitals NHS Foundation Trust; 3Hospital Universitario 12 de Octubre, Madrid, Spain; 4Istituto Nazionale Tumori – I.R.C.C.S. - Fondazione Pascale, Naples, Italy; 5Urologikum Hamburg, Hamburg, Germany; 6National Cancer Center Hospital East, Chiba, Japan; 7Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 8Seoul National University Hospital, Seoul, South Korea; 9Americas Medical City, Rio de Janeiro, Brazil; 10Janssen Global Services, Raritan, NJ, USA; 11Janssen Research & Development, Horsham, PA, USA; 12Janssen Research & Development, Shanghai, China; 13Janssen Research & Development, Beerse, Belgium; 14Janssen Research & Development, Buckinghamshire, UK; 15Gustave Roussy, University of Paris Sud, Villejuif, France

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Contents List of investigators for the LATITUDE study ............................................................................................... 3 CONSORT diagram ........................................................................................................................................ 8 Supplemental Figure 1. Patient-reported pain progression .............................................................................. 9 Supplemental Figure 2. Repeated-measures mixed-effects analysis of BPI-SF results ................................. 10 Supplemental Figure 3. Repeated-measures mixed-effects analysis of BFI results ...................................... 11 Supplemental Figure 4. Repeated-measures mixed-effects analysis of FACT-P total score and subscale .... 13 Supplemental Table 1: Schedule of Assessments .......................................................................................... 18 Supplemental Table 2: Predefined thresholds for pain progression and degradation in functional status ..... 19 Supplemental Table 3: Compliance data ....................................................................................................... 20 References cited in supplemental figures and tables ..................................................................................... 21 Statistical analysis plan for collection of PROs in LATITUDE .................................................................... 22

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List of investigators.*

Principal investigator Centre Location Patients enrolled, n

Mihai Harza Institutul Clinic Fundeni Bucuresti, Romania 26 Eugeny Kulikov Ryazan Regional Clinical Oncology Dispensary Ryazan, Russia 24 Anna Alyasova Clinical Diagnostical Center Nizhny Novgorod, Russia 19 Boris Alekseev Hertzen Oncology Research Institute Moscow, Russia 17 Jose Arturo Consultorio Privado Dr Jose Arturo Rodriguez Rivera Zapopan, Mexico 17 Gennadii Khareba Regional Clinical Center of Urology and Nefrology

NA Shapovalov V.I. Kharkiv, Ukraine 16

Mikhaik Shkolnik Russian Scientific Center of Radiology and Surgical Technologies

Saint Petersburg, Russia 16

Andrey Semenov Ivanovo Regional Oncology Dispensary Ivanovo, Russia 15 Viktor Stus Dnipropetrovsk State Clinical Hospital NA

Mechnikov I.I., Urology department #2 Dnipropetrovsk, Ukraine 15

Satoshi Fukasawa Chiba Cancer Center Chiba, Japan 14 Adel Izmaylov State Educational Istitution "Bashkir State Medical

University" Ufa, Russia 14

Nobuaki Matsubara National Cancer Center Hospital East Kashiwa, Japan 14 Valerii Sakalo State Institution "Institute of Urology NAMS of

Ukraine" based on Kyiv City Clinical Oncology Center

Kyiv, Ukraine 14

Zhiwen Chen Southwest Hospital, The Third Military Medical University

Chongqing, China 13

Jacek Jassem Uniwersyteckie Centrum Kliniczne Gdansk, Poland 13 Viorel Jinga Spitalul Clinic de Urologie Prof. Dr. Theodor

Burghele Bucharest, Romania 13

Vsevolod Matveev Cancer Research Center Moscow, Russia 13 Dominika Jaxa-Larecka Centrum Onkologii - Instytut im. M. Sklodowskiej-

Curie Warszawa, Poland 12

Peter Nyirady Semmelweis Egyetem, Urologiai Klinika Budapest, Hungary 12 Mustafa Ozguroglu Istanbul Universitesi Cerrahpasa TIP Fakultesi IC

Hastaliklari Anabilim Bali Medikal Oncoloji BD Istanbul,Turkey 12

Dingwei Ye Cancer Hospital, FuDan University Shanghai, China 12 Carlos Hernandez Oaxaca Site Management Organization S.C. Oaxaca, Mexico 11 Eli Rosenbaum Rabin Medical Center Petah-Tikva, Israel 11 Irina Adreyashkina Regional Oncology Dispansery #2 Saratov, Russia 10 Ugo De Giorgi Istituto Scientifico Romagnolo per lo Studio e la Cura

dei Tumori Meldola, Italy 10

Bhumsuk Keam Seoul National University Hospital Seoul, Korea 10 Joaquina Murício Instituto Portugues de Oncologia Porto, Portugal 10 Alfredo Rodríguez-Antolín Hospital 12 de Octubre Madrid, Spain 10 Zhangqun Ye Tongji Hospital, Tongji Medical College of

Huazhong University of Science and Technology Wuhan, China 10

Qing Zou Jiangsu Province Cancer Hospital Nanjing, China 10 Milan Gajdos Urologicka ambulancia Piestany, Slovakia 9 Andrea Juliana Gomes Liga Norte Riograndense Contra o Câncer Natal, Brazil 9 Eugene Hotko Uzhgorod Cenrtal City Hospital, city oncology center Uzhgorod, Ukraine 9 Yiran Huang Renji Hospital Affiliated to Medical College of

Shanghai Jiaotong University Shanghai, China 9

William Carlos Nahas ICESP – Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira

Sao Paulo, Brazil 9

Jose Palma dos Reis Hospital de Santa Maria Lisboa, Portugal 9 Mads Poulsen Odense University Hospital - SDR Boulevard 29 Odense, Denmark 9 Mingxing Qiu Sichuan Provincial People's Hospital Chengdu, China 9 Fangjian Zhou Sun Yat-Sen Cancer Center Guangzhou, China 9 Ronaldo Damião Americas Medical City Rio de Janiero, Brazil 8 Denis Khvorostenko State Medical Institution "Leningrad Regional

Oncological Center" St. Petersburg, Russia 8

Evgeny Kopyltsov Omsk Regional Clinical Hospital Omsk, Russia 8 Carlos Humberto Martinez Hospital Pablo Tobón Uribe Medellin, Colombia 8 Salvatore Natale Derriford Hospital Plymouth, Great Britain 8 Jacek Niezabitowski Wojewodzki Szpital Specjalistyczny w Lublinie Lublin, Poland 8 Anna Tran Christie Hospital Manchester, Great Britain 8

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Ben Wan Beijing Hospital Beijing, China 8 Luis Eduardo Zucca Hospital do Cancer De Barretos - Fundacao Pio XII Barretos, Brazil 8 Michael Borre Aarhus University Hospital Aarhus, Denmark 7 Lance JE Coetzee Urology Hospital Pretoria, South Africa 7 Luca Galli A.O.U. Pisana Pisa, Italy 7 Rob Jones Beatson West of Scotland Cancer Centre Glasgow, Great Britain 7 Evelyn Moshoka Clinical Research Unit, University of Pretoria Pretoria, South Africa 7 Ivan Pavlik Vseobecna fakultni nemocnice, I. interni klinika -

klinika hematologie Praha 2, Czech Republic 7

Andrew Protheroe Churchill Hospital Oxford, Great Britain 7 Mª José Requena Hospital Universitario Reina Sofia Cordoba, Spain 7 Fuminori Sato Oita University Hospital Yufu, Japan 7 Yinghao Sun Shanghai Changhai Hospital Shanghai, China 7 Hiroyoshi Suzuki Toho University Sakura Medical Center Sakura, Japan 7 Teuvo Tammela Tampere University Hospital Department of Surgery Tampere, Finland 7 Ferenc Torzsok Petz Aladar Megyei Oktato Korhaz, Urologia Gyõr, Hungary 7 Yuriy Vinnyk Kharkov Regional Clinical Oncology Dispensary Kharkov, Ukraine 7 Igor Bondarenko Dnepropetrovsk State Medical Academy -

Department of Oncology Dnepropetrovsk, Ukraine 6

Anatoly Bulanov Russian Cancer Research Center Moscow, Russia 6 David Calvo Consultorio de Especialidad en Urologia Privado Durango, Mexico 6 Jan-Erik Damber Urologmottagningen SU/Sahlgrenska Göteborg, Sweden 6 Luis Enrique Fein Centro Oncologico de Rosario Rosario, Argentina 6 Katsuyoshi Hashine National Shikoku Cancer Center Matsuyama, Japan 6 Jae-Lyun Lee Asan Medical Center Seoul, Korea 6 Alexandr Lykov Regional Oncological Dispansery Tumen, Russia 6 Inge Mejlholm Vejle Hospital, Department of Oncology Vejle, Denmark 6 Erich Mikucik Fakultna nemocnica Trnava Trnava, Slovakia 6 Ivan Mincik Milab s.r.o. Prešov, Slovakia 6 Elzbieta Oszukowska Specjalistyczne Gabinety Lekarskie Lodz, Poland 6 Anthony Beaven North Shore Hospital Auckland, New Zealand 5 Milos Brodak FN Hradec Kralove, Urologicka klinika Hradec Kralove, Czech

Republic 5

Kim Chi BC Cancer Agency - Vancouver Clinic Vancouver, Canada 5 Chuanjun Du The Second Affiliated Hospital of Zhejiang

University College of Medicine Hangzhou, China 5

Gaetano Facchini Istituto Nazionale dei Tumori di Napoli Fondazione G. Pascale

Napoli, Italy 5

Karim Fizazi Institut Gustave Roussy Villejuif Cedex, France 5 Fabio Franke Hospital de Caridade de Ijuí Ijuí, Brazil 5 Gustavo Girotto CIP – Centro Integrado de Pesquisa São José do Rio Preto 5 Hisashi Hasumi Yokohama City University Hospital Yokohama, Japan 5 Valeriy Hodos City clinical hospital # 10, department of Urology Odessa, Ukraine 5 Jie Jin Peking University, 1st Hospital Beijing, China 5 Daniel Keizman Meir Hospital Kfar Saba, Israel 5 Jan Kliment Univerzitná nemocnica Martin Martin, Slovakia 5 Kang Hyun Lee National Cancer Center Gyeonggi-do, Korea 5 Hiroaki Matsumoto Yamaguchi University Hospital Ube, Japan 5 Danish Mazhar Addenbrookes Hospital Cambridge, Great Britain 5 Yanqun Na Peking University Shougang Hospital Beijing, China 5 Claes Nyman Urologiska kliniken SÖS Stockholm, Sweden 5 Csaba Salamon Uro-Clin KFT Pécs, Hungary 5 Milton Salazar FOSCAL-FOSUNAB Floridablanca, Colombia 5 Scott Morgan The Ottawa Hospital Cancer Centre Ottawa, Canada 5 Carlos Silva Hospital S. Joao Porto, Portugal 5 Pavel Skopin Ogarev Mordovian State University Saransk, Russia 5 Sinan Sozen Gazi University Medical Faculty Hospital

Department of Urology Ankara, Turkey 5

Zhongquan Sun Huadong Hospital Affiliated to Fudan University Shanghai, China 5 Ye Tian Beijing Friendship Hospital Beijing, China 5 Raanan Berger Sheba Medical Center Tel Hashomer Ramat Gan, Israel 4 Sergio Bracarda Ospedale S. Donato – ASL 8 Arezzo Arezzo, Italy 4 Yuri Bychkov Russian Research Center of Roentgenology &

Radiology under the Federal Agency for Healthcare and Soc

Moscow, Russia 4

Ana Lucia Coradazzi Fundacao Hospital Amaral Carvalho Jau, Brazil 4 Natalia Fadeeva Chelyabinsk Regiona Onc. Center Chelyabinsk, Russia 4

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Susan Feyerabend Studienpraxis Urologie Nürtingen - Germany Nürtingen, Germany 4 Lajos Géczi Orszagos Onkologiai Intezet, C Kemoterapias

Osztaly Budapest, Hungary 4

Michael Häggman Urologiska kliniken Uppsala, Sweden 4 Jorgen Johansen Regionshospitalet Holsterbro Urologic department Holsterbro, Denmark 4 Luis Alberto Kaen Centro Oncologico Riojano Integral Cori La Rioja, Argentina 4 Oleg Karyakin Medical Radiological Research Center Obninsk, Kaluga Region,

Russia 4

Akos Lakatos Csongrád Megyei Dr Bugy István Kórház Szentes, Hungary 4 Börje Ljungberg Norrlands Universitetssjukhus, Urologiska Kliniken,

Umeå Umeå, Sweden 4

Lulin Ma Peking University Third Hospital Beijing, China 4 Thamsanqa SL Madlala East Rand Urology Research Unit Vosloorus, South Africa 4 Ruben Moreno Investigacion Biomedica Aplicada de Hidalgo S.A.

de C.V. Pachuca de Soto, Mexico 4

Alexander Nosov "Scientific Research Institute of Oncology n.a. Prof. N.N. Petrov"

St. Petersburg, Russia 4

David Olmos Centro Integral Oncológico Clara Campal Madrid, Spain 4 Nelson Orellana Uromed Santiago, Chile 4 Avivit Peer Rambam Hospital Haifa, Israel 4 Marniza Saad University Malaya Medical Centre Kuala Lumpur, Malaysia 4 Bobby Shayegan St. Josephs Healthcare Hamilton, Canada 4 Robert Siemens Centre for Applied Urology Research Kingston, Canada 4 Lionel Staudacher Hopital St Joseph Paris Cedex 14, France 4 Dmitry Tevs Sverdlovsk Region Clinical Hospital #1 Ekaterinburg, Russia 4 Tomohiro Tsuchiya Gifu University Hospital Gifu, Japan 4 Vladimir Vladimirov GBUZ of Stavropol region Pyatigorsk Oncological

Dispensary Pyatigorsk, Russia 4

Constantin Volovat Centrul de Oncologie-Euroclinic SRL Iaşi, Romania 4 Keji Xie Guangzhou First Municipal People's Hospital Guangzhou, China 4 Hwan Jung Yun Chungnam National University Hospital Daejeon, Korea 4 Pawel Zalewski RS McLaughlin Durham Oshawa, Canada 4 Umberto Basso Istituto Oncologico Veneto - IRCCS Padova, Italy 3 Anders Bjartell Skånes Universitetssjukhus Malmö, Sweden 3 Sara Martínez Breijo Hospital Juan Canalejo Coruña, Spain 3 Giacomo Cartenì Divisione di Oncologia Napoli, Italy 3 Paulo Conceição Instituto Português de Oncologia Francisco Gentil -

Centro Regional de Oncologia de Coimbra, S.A. Coimbra, Portugal 3

Qiang Ding Huashan Hospital of Fu Dan University Shanghai, China 3 Els Everaert A.Z. Nikolaas Sint-Niklaas 3 Neil Flesher Princess Margaret Hospital UHN Toronto, Canada 3 Yves Fradet CHUQ- L'Hotel-Dieu de Quebec Quebec, Canada 3 Avelino Fraga Hospital Geral de Santo Antonio Porto, Portugal 3 Elizabeth Hovey Prince of Wales Hospital Randwick, Australia 3 J.C.B. Hunting Sint Antonius Ziekenhuis - Afd.Interne - INT Nieuwegein, Netherlands 3 ChanKyu Kim Soonchunhyang University Bucheon Hospital Gyeonggi-Do, Korea 3 Frank Kueppers Canterbury Urology Research Trust Christchurch, New

Zealand 3

Carlos Larios Clinica Universitaria Colombia Bogota, Colombia 3 Hangzhong Li Peking Union Hospital Beijing, China 3 Estevao Lima Hospital de Braga Braga, Portugal 3 Oleksiy Lyulko Municipal Institution "Zaporizhzhia Regional Clinical

Hospital" Urology Department Zaporizhzhia, Ukraine 3

Bernardino Miñana Hospital General Universitario Morales Meseguer Murcia, Spain 3 Obaidullah Mir Urologická ambulancia Rimavska Sobota,

Slovakia 3

Scott North Cross Cancer Institute Edmonton, Canada 3 Mototsugu Oya Keio University Hospital Tokyo, Japan 3 Mehmet Ceyhun Ozyurt Ege Universitesi TIP Fakultesi Izmir, Turkey 3 Renato Panhoca Hospital do Servidor Publico Estadual Sao Paulo, Brazil 3 Luis Pinheiro Centro Hospitalar de Lisboa Central Lisboa, Portugal 3 Rodrigo Pinochet Hospital Dr Sotero del Rio Santiago, Chile 3 Tania Rodrigues Hospital da Luz Lisboa, Portugal 3 Avishay Sella Asaf Harofe Medical Center Beer Yaakov, Israel 3 Lyudmila Sheveleva Volgograd Region Oncology Dispensary Volgograd, Russia 3 Vadim Shirinkin GBUZ 'Orenburg Regional Oncology Dispensary' Orenburg, Russia 3 Henrik Suttman Urologikum Hamburg Hamburg, Germany 3

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Christine Theodore Hopital Foch Suresnes, France 3 Mahmut Gokhan Toktas Istanbul Egitim ve Arastirma Hastanesi Istanbul, Turkey 3 Hirotsugu Uemura Kindai University Hospital Osaka-Sayama, Japan 3 Wim Wynendaele Imelda ziekenhuis Bonheiden, Belgium 3 Liping Xie The First Affiliated Hospital, Zhejiang University

College of Medicine Hangzhou, China 3

Boxin Xue The Second Affiliatted Hospital of Soochow University

Su Zhou, China 3

Xin Yao Tianjin Medical University Cancer Hospital Tianjin, China 3 Massimo Aglietta Divisione di Oncologia - Istituto per la ricerca e cura

del cancro Candiolo, Italy 2

Emilio Jose Batagelj Hospital Militar Central “Cir. MY. DR. COSME Argerich”

Buenos Aires, Argentina 2

Yasar Beduk Ankara University Medical Faculty IBN-I SINA Hospital Department of Urology

Ankara, Turkey 2

Alfredo Berruti Spedali Civili di Brescia Brescia, Italy 2 Tomas Büchler Thomayerova nemocnice, Onkologicka klinika Praha 4, Czech Republic 2 Nikolay Budnik State Budgetary Institution of Rostov Region

"Hospital Veterans of War" Rostov-on-don, Russia 2

Joaquin Carballido Hospital Puerta de Hierro Madrid, Spain 2 Mesut Cetinkaya Ankara Numune Egitim Ve Arastirma Hastanesi 2.

Uroloji Klinigi Ankara, Turkey 2

Maciej Chwalinski Szpital Sw. Elzbiety Warszawa, Poland 2 Veronica Da Rosa Instituto do Cancer do Hospital Pompeia Caxias do Sul, Brazil 2 Jean de la Rosette AMC Amsterdam Zuidoost,

Netherlands 2

Jozsef Feher Baz Megyei Korhaz es Egyetemi Oktato Korhaz Miskolc, Hungary 2 Peter Gilling Tauranga Urology Research Limited Tauranga, New Zealand 2 M.P. Hendriks Medisch Centrum Alkmaar Alkmaar, Netherlands 2 Milan Hora Fakultni nemocnice Plzen, Urologicka klinika Plzen, Czech Republic 2 Hiroomi Kanayama Tokushima University Hospital Tokushima, Japan 2 Galina Kurteva Specialized Hospital for Active Treatment in

Oncology Sofia, Bulgaria 2

Changling Li Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, China 2

Wilmosh Mermershtain Soroka Hospital Beer-Sheva, Israel 2 Sergio Victorio Metrebian Hospital Privado de Cordoba Cordoba Capital,

Argentina 2

Igor Milichovsky Nemocnica Košice-Šaca Košice-Šaca, Slovakia 2 Jamie Mills Nottingham City Hospital NHS Trust Nottingham, Great

Britain 2

Juan Morote Hospital Universitario Vall d´Hebron Barcelona, Spain 2 Aydin Mungan Bulent Ecevit Universitesi TIP Fakultesi Hastanesi Zonguldak, Turkey 2 Haluk Ozen Hacettepe University Department of Urology Ankara, Turkey 2 Viktor Paramonov Cherkassy Regional Oncology Dispensary,

chemotherapy department Cherkassy, Ukraine 2

Se Hoon Park Samsung Medical Center Seoul, Korea 2 Maria Jose Ribal Hospital Clinic I Provincial Barcelona, Spain 2 Yaroslav Shparyk Lviv State Regional Oncology Medical and

Diagnostic Center, chemotherapy department Lviv, Ukraine 2

Murali Sundram Hospital Kuala Lumpur Kuala Lumpur, Malaysia 2 Hsiang Tan Royal Adelaide Hospital Adelaide, Australia 2 Yiloren Tanidir Marmara Universitesi TIP Fakultesi Pendix Egitim ve

Arastirma Hastanesi Istanbul, Turkey 2

Zuhtu Tansug Cukurova Universitesi TIP Fakultesi Adana, Turkey 2 Giuseppe Tonini Università Campus Biomedico di Roma Roma, Italy 2 Markku Vaarala Oulu University Hospital Department of Urology Oulo, Finland 2 H.P. van den Berg Ziekenhuis Hilversum Hilversum, Netherlands 2 Vincent Verschaeve Clinique Notre Dame Charleroi, Belgium 2 Hans-Erik Wittendorf Roskilde Hospital department of urology Roskilde, Denmark 2 Johann C.M. Bahlmann Private practice George, South Africa 1 Wei Chua Liverpool Hospital Liverpool, Australia 1 Wim Demey AZ Klina Brasschaat, Belgium 1 Lionel D’Hondt UCL de Mont-Godinne Yvoir, Belgium 1 Sergey Emelyanov Republican Clinical Oncology Dispensary Izhevsk, Russia 1 Stephen Frank Hadassah Hospital Jerusalem, Israel 1 Mark Frydenberg Australian Urology Associates Pty Ltd Malvern, Australia 1

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Joel Gingerich Cancer Care Manitoba Winnipeg, Canada 1 Michael Holmes Urology Waikato Ltd Hamilton, New Zealand 1 Byung Woog Kang Kyungpook National University Medical Center Daegu, Korea 1 YeulHong Kim Korea University Anam Hospital Seoul, Korea 1 Ernesto Korbenfeld Hospital Britanico de Buenos Aires Urologica Buenos Aires, Argentina 1 Philippe Laplaige Polyclinique de Blois La Chaussee St Victor,

France 1

Jorn R. Malan Langenhoven Drive Oncology Port Elizabeth, South Africa

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Alberto Nogueira CENOB – Centro de Oncologia da Bahia – Oncovida Salvador, Brazil 1 Rodolfo Reis Hospital das Clínicas da Faculdade de Medicina da

USP de Ribeirão Preto Ribeirão Preto, Brazil 1

Fred Saad Hopital Notre Dame Montreal, Canada 1 Antonio Orlando Scalabrini-Neto

Universidade Federal de Minas Gerais Belo Horizonte, Brazil 1

Dirk Schrijvers ZNA Middelheim Antwerpen, Belgium 1 Santiago Solano Clínica del Country Bogota, Colombia 1 Esteban Staneloni Sanatoria Güemes Buenos Aires, Argentina 1 Thomas Steuber Martini-Klinik am UKE Hamburg Eppendorf -

Germany Hamburg, Germany 1

Piotr Swiniarski 10 Wojskowy Szpital Kliniczny z Poliklinika, Samodzielny Zaklad Opieki Zdrowotnej

Bydgoszcz, Poland 1

Giampaolo Tortora Azienda Ospedaliera Universitaria Integrata Verona Verona, Italy 1 R.J.A. van Moorselaar VU Medisch Centrum Amsterdam, Netherlands 1 Arnauld Villers Hopital Huriez Lille, France 1 David Waltregny Comité d'Ethique Hospitalo-Facultaire de Lièg Liège, Belgium 1 Nicolas Whenham Clinique St Pierre Ottignies, Belgium 1 Henry Woo Australian Clinical Trials - SAN Clinic Wahroonga, Australia 1 *Investigators are listed in descending order by number of patients enrolled in the study.

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CONSORT diagram.1

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Supplemental Figure 1: Patient-reported pain progression Kaplan-Meier curve for time to BPI-SF average pain progression.

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Supplemental Figure 2: Repeated-measures mixed-effects analysis of BPI-SF results Average pain score. Each cycle was 28 days long.

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Supplemental Figure 3: Repeated-measures mixed-effects analysis of BFI results Mean change from baseline in worst fatigue intensity score (A) and fatigue interference score (B). Each cycle was 28 days long.

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Supplemental Figure 4: Repeated-measures mixed-effects analysis of FACT-P total score and subscale Mean change from baseline in FACT-G subscale (A); trial outcomes index (B); pain-related subscale (C); prostate cancer–specific subscale (D); emotional wellbeing subscale (E); functional wellbeing subscale (F); physical wellbeing subscale (G); and social/family wellbeing subscale (H). Each cycle was 28 days long.

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Supplemental Table 1: Schedule of Assessments

Screening phase Double-blind treatment phase Follow-up phase*

Parameter

Within 2 days prior to

randomisation

Pretreatment on day 1 of cycles

1–13

Pretreatment every other

month/ cycle from

cycle 14 until clinical or

radiographic progression

End-of-treatment visit, within 30

days of last dose Every 4 months for a total of 12 months up to 60 months

BPI-SF X X X X

BFI X X X X

FACT-P X X X X

EQ-5D-5L X X X X X

*Upon completion of the follow-up phase, patients from the placebo arm were allowed to cross over to active treatment in an open-label extension phase. FACT-P and EQ-5D-5L assessments are being collected in the open-label extension phase, using a schedule similar to that used in the treatment phase.

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Supplemental Table 2: Predefined thresholds for pain progression and degradation in functional status

Change threshold Total possible score Description

BPI-SF2-6

Progression of worst pain intensity (question 3) Increase ≥30% from baseline* 10 BPI-SF is a well-established tool that evaluates several aspects of pain and pain interference with daily living. Patients evaluate each item on a scale of 0 to 10, with a lower score indicating a lower level of pain or pain interference with daily activities

Progression of pain interference with daily living (mean of question 9 subparts) Increase ≥50% of baseline SD 10

FACT-P

Total score7† 10-point decrease/worsening from baseline 156

FACT-P is a well-established tool for assessing HRQoL in patients with prostate cancer.7 A higher score indicates more favourable HRQoL

FACT-G general function7‡ 9-point decrease/worsening from baseline 108

Trial outcome index7§ 9-point decrease/worsening from baseline 104

Prostate cancer–specific subscale7 3-point decrease/worsening from baseline 48

General function subscales8 3-point decrease/worsening from baseline 48

BFI

Worst fatigue (question 3) 2-point increase from baseline 10 The BFI is a well-established tool that evaluates fatigue and fatigue interference with daily activities on a scale of 0 to 10, with a lower score indicating a lower level of fatigue or fatigue interference with daily activities

Fatigue interference progression9 1·25-point increase from baseline 10

*Observed at 2 consecutive evaluations ≥4 weeks apart. †Including general function and prostate cancer–specific subscale scores. ‡ Including physical, social and family, emotional, and functional wellbeing subscales. §Including physical and functional wellbeing and prostate cancer–specific subscales.

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Supplemental Table 3: Compliance data Compliance across both treatment arms, n/N (%) BPI-SF FACT-P BFI EQ-5D-5L Baseline 1149/119 (96) 1147/1199 (96) 1146/1199 (96) 1148/1199 (96) Cycle 2 1174/1199 (98) 1171/1199 (98) 1172/1199 (98) 1174/1199 (98) Cycle 3 1144/1184 (97) 1144/1184 (97) 1143/1184 (97) 1148/1184 (97) Cycle 4 1133/1168 (97) 1131/1168 (97) 1134/1168 (97) 1132/1168 (97) Cycle 5 1102/1146 (96) 1104/1146 (96) 1104/1146 (96) 1104/1146 (96) Cycle 6 1059/1112 (95) 1058/1112 (95) 1058/1112 (95) 1061/1112 (95) Cycle 7 1034/1072 (97) 1032/1072 (96) 1034/1072 (97) 1035/1072 (97) Cycle 8 991/1035 (96) 989/1035 (96) 989/1035 (96) 991/1035 (96) Cycle 9 960/1006 (95) 960/1006 (95) 960/1006 (95) 962/1006 (96) Cycle 10 923/965 (96) 921/965 (95) 921/965 (95) 924/965 (96) Cycle 11 874/909 (96) 874/909 (96) 874/909 (96) 874/909 (96) Cycle 12 854/889 (96) 851/889 (96) 853/889 (96) 855/889 (96) Cycle 13 832/866 (96) 831/866 (96) 832/866 (96) 832/866 (96) Cycle 15 772/833 (93) 770/833 (92) 771/833 (93) 773/833 (93) Cycle 17 702/763 (92) 701/763 (92) 701/763 (92) 703/763 (92) Cycle 19 657/699 (94) 657/699 (94) 657/699 (94) 657/699 (94) Cycle 21 598/648 (92) 598/648 (92) 598/648 (92) 601/648 (93) Cycle 23 549/602 (91) 549/602 (91) 549/602 (91) 548/602 (91) Cycle 25 521/557 (94) 521/557 (94) 521/557 (94) 522/557 (94) Cycle 27 460/500 (92) 458/500 (92) 460/500 (92) 459/500 (92) Cycle 29 393/430 (91) 393/430 (91) 393/430 (91) 393/430 (91) Cycle 31 340/373 (91) 340/373 (91) 340/373 (91) 343/373 (92) Cycle 33 277/300 (92) 277/300 (92) 277/300 (92) 276/300 (92) Cycle 35 207/223 (93) 207/223 (93) 206/223 (92) 207/223 (93) Cycle 37 162/168 (96) 162/168 (96) 162/168 (96) 162/168 (96) Cycle 39 109/118 (92) 109/118 (92) 109/118 (92) 109/118 (92) Cycle 41 77/85 (91) 77/85 (91) 77/85 (91) 77/85 (91) Cycle 43 51/55 (93) 51/55 (93) 51/55 (93) 51/55 (93) Cycle 45 27/30 (90) 27/30 (90) 27/30 (90) 27/30 (90) Cycle 47 4/4 (100) 4/4 (100) 4/4 (100) 4/4 (100) Note: Reasons for missing PROs were not centrally recorded.

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22Approved, Date: 5 December 2016

Janssen Research & Development *

Statistical Analysis Plan

PRO Endpoints

Protocol 212082PCR3011; Phase 3

JNJ-212082 (abiraterone acetate)

Status: Approved

Date: 5 December 2016

Prepared by: Janssen Research & Development

Document No.: EDMS-ERI-134816070, 1.0

Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP).

Confidentiality StatementThe information in this document contains trade secrets and commercial information that are privileged or confidential and may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom theinformation is disclosed must be informed that the information is privileged or confidential and may not be further disclosedby them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or confidential.

JNJ-212082 (abiraterone acetate)Statistical Analysis Plan 212082PCR3011


TABLE OF CONTENTS

TABLE OF CONTENTS ............................................................................................................................... 23

1. OBJECTIVES ...................................................................................................................................... 241.1. Research Questions and Study Objectives ..................................................................................... 24

2. METHODS ........................................................................................................................................... 242.1. PRO Time and Events Schedule ..................................................................................................... 242.2. PRO Scales/Variables...................................................................................................................... 242.2.1. Brief Pain Inventory – Short Form (BPI-SF) ................................................................................. 242.2.2. Functional Assessment of Cancer Therapy-Prostate (FACT-P) .................................................. 252.2.3. Brief Fatigue Inventory (BFI) ........................................................................................................ 252.2.4. EQ-5D-5L...................................................................................................................................... 252.2.5. List of PRO Scales........................................................................................................................ 262.3. Analysis Methods ............................................................................................................................. 262.3.1. Tabulation of Missing PRO Forms................................................................................................ 272.4. Descriptive Statistics Over Time...................................................................................................... 272.5. Time to PRO Progression/Deterioration ......................................................................................... 272.6. Repeated Measures Model of PRO .................................................................................................30

REFERENCES............................................................................................................................................ 31

APPENDIX 1: FACT-PROSTATE QUESTIONNAIRES AND SCORING GUIDELINE............................. 32



1. OBJECTIVES

1.1. Research Questions and Study Objectives

The major research question is whether abiraterone acetate postpones pain progression and

functional status deterioration, as part of the secondary objectives to evaluate the clinically

relevant improvements of abiraterone acetate plus low dose prednisone plus androgen

deprivation therapy (ADT) versus ADT alone in newly diagnosed subjects with high risk,

metastatic hormone-naive prostate cancer.

This analysis plan describes pre-specified analyses of the PRO measures collected in Study

212082PCR3011.

2. METHODS

2.1. PRO Time and Events Schedule

Table 1 below shows the expected data collection points for each of the PRO measures. For

analysis purposes, the last available value collected prior to the first dose of study drug will be

used as the baseline value.

Table 1: Schedule of PRO Data Collection

Treatment Visit

Brief Pain Inventory-Short Form (BPI-SF)

Functional Assessment of Cancer Therapy–Prostate (FACT-P)

Brief Fatigue Inventory (BFI)

EQ-5D-5L

Baselinea

X X X X

q1M from Cycle 2 to Cycle 13, then q2M until radiographic or clinical progression

X X X X

End of Study Treatment Visit X X X X

Q4M for a total of 12months after radiographic or clinical progression

X

a Only 1 baseline PRO assessment is required. Baseline PRO assessments can occur either within 2 days prior to randomization or on Cycle 1 Day 1 (before any procedures are performed)

2.2. PRO Scales/Variables

2.2.1. Brief Pain Inventory – Short Form (BPI-SF)

The BPI-SF which is a validated tool consists of four (4) questions regarding pain intensity (pain

at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on the average, and pain

you have right now), two questions on the use of analgesics, and seven questions on the level

pain has interfered with the subject’s general activity, mood, walking ability, normal work,



relations with other people, sleep and enjoyment of life. The five BPI-SF scales to be analyzed

here are the BPI-SF Worst Pain Intensity (item 3), Least Pain Intensity (item 4), Average Pain

Intensity (item 5), Pain Intensity Right Now (item 6), and the BPI-SF Interference scale. The

four BPI-SF Intensity scales are 11-response numerical rating scales scored from zero (0) to ten

(10), with zero representing “No Pain” and ten representing “Pain As Bad As You Can Imagine.”

The BPI-SF Interference scale is derived from the seven items asking about the impact of pain on

interference with activities, combining scale scores from items 9a through 9g; where each of the

seven items is an 11-response numerical rating scale scored from zero (0) to ten (10), with zero

representing “Does Not Interfere” and ten representing “Completely Interferes”. The BPI-SF

Interference scale is the mean of non-missing items, if there are four or more items not missing;

otherwise this scale is set to missing.

2.2.2. Functional Assessment of Cancer Therapy-Prostate (FACT-P)

Scoring guidelines for the FACT-P which is well validated, as well as handling of missing items

(as opposed to missing assessments) will be in accordance with methodology described in the

Manual of the Functional Assessment of Chronic Illness Therapy (FACIT) Measurement

System, version 4.0 (November 1997). See Appendix 1. The scales from the FACT-P are

composed of the following items, all with higher scores indicating better functioning:

PWB: items GP1-GP7 (scale values range from 0 to 28),

SFWB: items GS1-GS7 (scale values range from 0 to 28),

EWB: items GE1-GE6 (scale values range from 0 to 24),

FWB: items GF1-GF7 (scale values range from 0 to 28),

FACT-G: items from the PWB, SFWB, EWB, and FWB (scale values range from 0 to 108),

PCS: the 12 items from the additional concerns section (scale values range from 0 to 48),

TOI: PWB, FWB, and PCS scales (scale values range from 0 to 104), and

FACT-P: scales FACT-G and PCS (scale values range from 0 to 156)

2.2.3. Brief Fatigue Inventory (BFI)

The BFI which is a validated tool consists of three questions assessing the severity of fatigue and

six questions assessing the impact of fatigue on the subject’s mood, social functioning and

physical functioning. Each question is asked in relation to the last 24 hours and is scored on an

11-point numerical rating scale, with higher scores indicating greater fatigue and interference

with functionality.

2.2.4. EQ-5D-5L

The EQ-5D-5L1 is a validated tool that measures mobility, self-care, usual activities,

pain/discomfort, and anxiety/depression. The EQ-5D quality of life instrument consists of a 5-

item questionnaire and a visual analogue scale ranging from 0 (worst imaginable health state) to

100 (best imaginable health state) that integrates many aspects of the subject’s disease process

into a single assessment.



2.2.5. List of PRO Scales

All PRO scales included in the analyses specified here are listed below. The BPI-SF Worst Pain

Intensity, the FACT-P PCS and Total score are considered the primary PRO scales.

BPI-SF

Worst Pain (Item 3)

Pain Interference score (combination of BPI scale scores 9a through 9g)

Average pain (Average of Items 3-6)

FACT-P

PWB

SFWB

EWB

FWB

FACT-G

PCS

TOI

FACT-P Total

FACT-P Pain Scale (average of P1-P3, and GP)

BFI

Worst Fatigue (Item 3)

Fatigue Interference (Average of Items 4A-4F)

EQ-5D-5L

Health State

EQ VAS score

2.3. Analysis Methods

All analysis will be performed by treatment arm.

Based on the PRO assessment date, the associated visit will be mapped and used for analysis. For

subjects with multiple records at the same visit, the closest one to the visit date will be selected

as scheduled assessment, and others will be unscheduled assessments. For those with multiple

records on the same assessment date, the first one by time point and sequence number is assumed

to be selected as scheduled assessment. Only scheduled assessments will be included in the by-

visit analysis, while all assessments will be included in time-to-event analysis.



2.3.1. Tabulation of Missing PRO Forms

Missing PRO assessments defined as the expected number of assessments for a particular visit

minus the actual number of assessments for that visit will be tabulated by treatment group and

overall for each baseline, each cycle, end of treatment, and cumulatively. Separate tables will be

constructed for each PRO Form. Expected number of assessments per visit will be determined

by subject-level study completion status. These tables will resemble the example in Table 2,

below.

Table 2: Sample Table of Compliance with PRO Assessment

Timing of Assessment1

AA+P+ADT (N = xxx) ADT (N = xxx) Total (N = xxx)Number of Forms, n (%) Number of Forms, n (%) Number of Forms, n (%)

Expected Received Missing Expected Received Missing Expected Received Missing

Baseline Xxx xx (xx.x) xx (xx.x) Xxx xx (xx.x) xx (xx.x) xxx xx (xx.x) xx (xx.x)Cycle 2 Xxx xx (xx.x) xx (xx.x) Xxx xx (xx.x) xx (xx.x) xxx xx (xx.x) xx (xx.x)Cycle 3 Xxx xx (xx.x) xx (xx.x) Xxx xx (xx.x) xx (xx.x) xxx xx (xx.x) xx (xx.x)Cycle 4 Xxx xx (xx.x) xx (xx.x) Xxx xx (xx.x) xx (xx.x) xxx xx (xx.x) xx (xx.x)… Xxx xx (xx.x) xx (xx.x) Xxx xx (xx.x) xx (xx.x) xxx xx (xx.x) xx (xx.x)Total Xxx xx (xx.x) xx (xx.x) Xxx xx (xx.x) xx (xx.x) xxx xx (xx.x) xx (xx.x)Note: Percentages calculated with the number of expected forms in each group as denominator1 The End of Treatment assessment may occur at the last scheduled cycle or at some other time for patients who discontinue. To avoid

double-counting of assessments and to standardize the measurement points, the end of treatment assessment will be parsed out to its appropriate cycle assessment.

2.4. Descriptive Statistics Over Time

Descriptive statistics (number of observations, mean, standard deviation, minimum, maximum)

of scores at baseline and follow-up assessments, by treatment groups will be produced for each

PRO scale. Plots of mean score at assessment, by treatment group (showing number of subjects

at each visit) will be produced. For these descriptive statistics, and for all analyses specified

below, the scores obtained at the end of study treatment visit will be assigned a cycle number as

the next cycle that would have been completed if the subject were to have continued receiving

study treatment.

For EQ-5D-5L Scores, frequency count and percentage of each reporting level (1 to 5) over Time

will be provided.

2.5. Time to PRO Progression/Deterioration

Progression/deterioration is defined based on a clinically meaningful threshold for each specific

PRO scale. Table 3 summarizes the threshold values for determining a PRO

progression/deterioration. Time to progression/deterioration will be defined as the time interval

from randomization to the first date a patient experiences a clinically meaningful threshold

change. Subjects who did not experience progression/deterioration will be censored at their last

available PRO assessment. Time to progression/deterioration will be compared between 2

treatment groups.

Time to pain progression was defined as the time interval from randomization to the first date a

patient experience an increase by ≥30% from baseline in the BPI-SF worst pain intensity item



(item 3) observed at 2 consecutive evaluations ≥4 weeks apart. Subjects who have not

experienced pain progression at the time of analysis will be censored on the last known date

when a patient was known to have not progressed. Subjects with no on-study assessment or no

baseline assessment will be censored at date of randomization. As sensitivity analysis, time to

progression in worst intensity pain may be defined as 2-point increase from baseline and

compared between the treatment groups.

A change of one half standard deviation of baseline BPI-SF interference score is the threshold

value for deterioration of the BPI-SF Pain Interference scale. Time to pain interference

progression was defined as the time interval from randomization to the first date a patient

experience an increase of the threshold value specified by one half the standard deviation of

baseline scores from baseline in the BPI-SF pain interference items.

Time to fatigue intensity progression was defined as the time interval from randomization to the

first date a patient experience an increase by ≥2 points from baseline in the worst BFI intensity

item (item 3) observed at 2 consecutive evaluations ≥4 weeks apart. Fatigue interference

progression was defined as an increase of ≥1.25 points from baseline in the average BFI

interference score observed at 2 consecutive evaluations ≥4 weeks apart.2 Subjects who have not

experienced fatigue progression at the time of analysis will be censored on the last known date a

patient was known to have not progressed. The subjects with no on-study assessment or no

baseline assessment will be censored at date of randomization

Change thresholds for deterioration on the FACT-P PCS, TOI, and FACT-P Total scales are

based upon an article,3 which provided clinically meaningful change estimates in a prostate

cancer sample based upon an anchoring methodology). The FACT-G scales (PWB, SFWB,

EWB, FWB, and the FACT-G) were not addressed in that article, and so the clinically

meaningful change estimates for those scales are derived from an earlier article,4 which reports

normative values from a large sample from the general population for the FACT-G scales.

Standard deviations (once normalized back to their original scales from the zero to 100 scale

reported in the article) for the PWB, SFWB, EWB, FWB, and the FACT-G were 5.35, 6.80,

4.78, 6.83, and 18.04, respectively. Taking one half the standard deviation is equivalent to

finding a 0.5 effect size. Using this distributional technique to find the clinically meaningful

change estimates produced values of about 3 points for PWB, SFWB, EWB, and FWB and about

9 points for the FACT-G.



Table 3: Time to progression/Deterioration Thresholds

Scale/Sub-Scale Threshold for definition of progression/deteriorationBPI-SF (Increase from baseline)

Worst Pain (BPI3) ≥30% of baseline≥2 point **

Pain Interference score (combination of BPI scale scores 9a through 9g)

≥ half standard deviation of baseline

Average pain (Average of BPI3-6) ≥30% of baseline

BFI (Increase from baseline)

Worst Fatigue (BFI 3) ≥2 point

Fatigue Interference Progression ≥1.5 point

FACT-P (decrease from baseline)

Physical Well-Being (PWB) 3

Social/Family Well-Being (SFWB) 3

Emotional Well-Being (EWB) 3

Functional Well-Being (FWB) 3

FACT-G (General) Scale 9

Prostate Cancer Subscale (PCS) 3

Trial Outcome Index (TOI) 9

FACT-P Total Scale 10

FACT-P Pain Scale 2** sensitivity analysis

The table below lists the time to progression/deterioration analyses to be performed. For each

PRO endpoint, the median time to deterioration will be estimated using a Kaplan-Meier method.

Additionally, hazard ratio (AA+P+ADT / ADT) will be estimated by fitting Cox’s proportional

hazards model stratified by baseline ECOG and visceral status. In cases where median values

cannot be computed because less than 50% of subjects experienced progression/deterioration,

25th percentiles will be reported and compared instead.

Table 4: Time to PRO Progression/Deterioration, Zytiga plus Low dose Prednisone Plus Androgen Deprivation Therapy (ADT) Versus ADT Alone

PRO Measure Median # of Months to Progression/Deterioration Hazard ratio (95%

Confid. Interval)P-value

Time to progression/deterioration AA+P+ ADT

ADT

BPI-SF Progression

Worst Pain Intensity N N x.xxx (x.xxx, x.xxx) 0.xxxx

Average Pain ScorePain Interference

NN

NN

x.xxx (x.xxx, x.xxx)x.xxx (x.xxx, x.xxx)

0.xxxx0.xxxx

FACT-P Deterioration

FACT-P Total Scale N N x.xxx (x.xxx, x.xxx) 0.xxxx

FACT-P PCSFACT-P PWBFACT-P SFWBFACT-P EWBFACT-P FWBFACT-P TOIFACT-G

NNNNNNN

NNNNNNN

x.xxx (x.xxx, x.xxx)x.xxx (x.xxx, x.xxx)x.xxx (x.xxx, x.xxx)x.xxx (x.xxx, x.xxx)x.xxx (x.xxx, x.xxx)x.xxx (x.xxx, x.xxx)x.xxx (x.xxx, x.xxx)

0.xxxx0.xxxx0.xxxx0.xxxx0.xxxx0.xxxx0.xxxx

Hazard ratio is from stratified proportional hazards model. Hazard ratio <1 favors AA-P. P value is from a log-rank test stratified by ECOG PS score (0/1 or 2) and visceral (absent or present).



2.6. Repeated Measures Model of PRO

For each PRO scale, repeated measures mixed effect model will be fitted to estimate the mean

PRO scores at each cycle.5 In this model the dependent variable will be the PRO score change

from baseline. Fixed effects for the models will include, treatment and visit number as discrete

parameters, and interaction between time and treatment; subject is included as random effect.

Serial correlation is assumed, and a AR(1) correlation matrix will be explored, if appropriate, to

account for the correlations between repeated measures within subjects. Lsmeans of change

from baseline will be plotted for each PRO scale, by cycle and treatment group. T-tests will be

performed to test for the differences in mean PRO scores between treatment groups at each

cycle. In the event of a significant amount of missing data during final treatment cycles,

truncation will be applied for all subsequent visits at the first visit where 90% or more of the

subjects are missing for any endpoint and from either arm. Once the truncation cycle is

determined, this cycle will be applied across both treatment arms.



REFERENCES

1. EQ-5D-5L User Guide.http://www.euroqol.org/fileadmin/user_upload/Documenten/PDF/Folders_Flyers/UserGuide_EQ-5D-5L_v2.0_October_2013.pdf

2. C. N. Sternberg, A. Molina, S. North, P. Mainwaring, K. Fizazi, Y. Hao, M. Rothman, D. D. Gagnon,T. Kheoh, C. M. Haqq, C. Cleeland, J. S. de Bono, H. I. Scher. Effect of abiraterone acetate on fatigue inpatients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy. Annals of Oncology24(4): 1017-1025, 2013.

3. Cella D, Nichol MB, Eton D, Nelson JB, Mulani P. Estimating Clinically Meaningful Changes for theFunctional Assessment of Cancer Therapy—Prostate: Results from a Clinical Trial of Patients with MetastaticHormone-Refractory Prostate Cancer. Value in Health 12(1): 124-129, 2009.

4. Cella D, Zagari MJ, Vandoros C, Gagnon DD, Hurtz HJ, and Nortier JWR. Epoetin Alfa Treatment Results inClinically Significant Improvements in Quality of Life in Anemic Cancer Patients When Referenced to theGeneral Population. JCO 21(2): 366-373, 2003.

5. Fitzmaurice G, Laird N, Ware J. Applied Longitudinal Analysis, 2004



APPENDIX 1: FACT-PROSTATE QUESTIONNAIRES AND SCORING GUIDELINE

Below is a list of statements that other people with your illness have said are important. Please

circle or mark one number per line to indicate your response as it applies to the past 7

days.

PHYSICAL WELL-BEING Not at all

A little bit

Some-what

Quitea bit

Very much

GP1 I have a lack of energy 0 1 2 3 4GP2 I have nausea 0 1 2 3 4GP3 Because of my physical condition, I have trouble meeting the needs of

my family 0 1 2 3 4GP4 I have pain 0 1 2 3 4GP5 I am bothered by side effects of treatment 0 1 2 3 4GP6 I feel ill 0 1 2 3 4GP7 I am forced to spend time in bed 0 1 2 3 4

SOCIAL/FAMILY WELL-BEING Not at all

A little bit

Some-what

Quitea bit

Very much

GS1 I feel close to my friends 0 1 2 3 4GS2 I get emotional support from my family 0 1 2 3 4GS3 I get support from my friends 0 1 2 3 4GS4 My family has accepted my illness 0 1 2 3 4GS5 I am satisfied with family communication about my illness

0 1 2 3 4GS6 I feel close to my partner (or the person who is my main support)

0 1 2 3 4

Q1 Regardless of your current level of sexual activity, please answer the following question. If you prefer not to answer it, please mark this box and go to the next section.

GS7 I am satisfied with my sex life 0 1 2 3 4



Please circle or mark one number per line to indicate your response as it applies to the past

7 days.

EMOTIONAL WELL-BEING Not at all

A little bit

Some-what

Quitea bit

Very much

GE1 I feel sad 0 1 2 3 4GE2 I am satisfied with how I am coping with my illness 0 1 2 3 4GE3 I am losing hope in the fight against my illness 0 1 2 3 4GE4 I feel nervous 0 1 2 3 4GE5 I worry about dying 0 1 2 3 4GE6 I worry that my condition will get worse 0 1 2 3 4

FUNCTIONAL WELL-BEING Not at all

A little bit

Some-what

Quitea bit

Very much

GF1 I am able to work (include work at home) 0 1 2 3 4GF2 My work (include work at home) is fulfilling 0 1 2 3 4GF3 I am able to enjoy life 0 1 2 3 4GF4 I have accepted my illness 0 1 2 3 4GF5 I am sleeping well 0 1 2 3 4GF6 I am enjoying the things I usually do for fun 0 1 2 3 4GF7 I am content with the quality of my life right now 0 1 2 3 4

Please circle or mark one number per line to indicate your response as it applies to the past 7 days.

ADDITIONAL CONCERNS Not at all

A little bit

Some-what

Quitea bit

Very much

C2 I am losing weight 0 1 2 3 4C6 I have a good appetite 0 1 2 3 4P1 I have aches and pains that bother me 0 1 2 3 4P2 I have certain parts of my body where I experience pain 0 1 2 3 4P3 My pain keeps me from doing things I want to do 0 1 2 3 4P4 I am satisfied with my present comfort level 0 1 2 3 4P5 I am able to feel like a man 0 1 2 3 4P6 I have trouble moving my bowels 0 1 2 3 4P7 I have difficulty urinating 0 1 2 3 4BL2 I urinate more frequently than usual 0 1 2 3 4P8 My problems with urinating limit my activities 0 1 2 3 4BL5 I am able to have and maintain an erection 0 1 2 3 4



FACT-P Scoring Guidelines (Version 4) – Page 1

Instructions:* 1. Record answers in "item response" column. If missing, mark with an X2. Perform reversals as indicated, and sum individual items to obtain a score.3. Multiply the sum of the item scores by the number of items in the subscale,then divide by the number of items answered. This produces the subscale score.4. Add subscale scores to derive total scores (TOI, FACT-G & FACT-P).5. The higher the score, the better the QOL.

Subscale Item Code Reverse item? Item response Item Score

PHYSICAL GP1 4 - ________ =________WELL-BEING GP2 4 - ________ =________ (PWB) GP3 4 - ________ =________

GP4 4 - ________ =________ GP5 4 - ________ =________

GP6 4 - ________ =________GP7 4 - ________ =________

Sum individual item scores: ________ Multiply by 7: ________

Divide by number of items answered: ________=PWB subscale score

SOCIAL/FAMILY GS1 0 + ________ =________WELL-BEING GS2 0 + ________ =________ (SWB) GS3 0 + ________ =________

GS4 0 + ________ =________ GS5 0 + ________ =________

GS6 0 + ________ =________GS7 0 + ________ =________


Divide by number of items answered: ________=SWB subscale score

EMOTIONAL GE1 4 - ________ =________WELL-BEING GE2 0 + ________ =________ (EWB) GE3 4 - ________ =________

GE4 4 - ________ =________ GE5 4 - ________ =________

GE6 4 - ________ =________


Divide by number of items answered: ________=EWB subscale score

FUNCTIONAL GF1 0 + ________ =________WELL-BEING GF2 0 + ________ =________ (FWB) GF3 0 + ________ =________

GF4 0 + ________ =________ GF5 0 + ________ =________ GF6 0 + ________ =________

GF7 0 + ________ =________


Divide by number of items answered: ________=FWB subscale score

Score range: 0-28

Score range: 0-28

Score range: 0-24

Score range: 0-28



FACT-P Scoring Guidelines (Version 4) – Page 2


PROSTATE C2 4 - ________ =________CANCER C6 0 + ________ =________SUBSCALE P1 4 - ________ =________ (PCS) P2 4 - ________ =________

P3 4 - ________ =________P4 0 + ________ =________P5 0 + ________ =________P6 4 - ________ =________P7 4 - ________ =________BL2 4 - ________ =________P8 4 - ________ =________BL5 0 + ________ =________

Sum individual item scores:________ Multiply by 12: ________

Divide by number of items answered: ________=PC Subscale score

To derive a FACT-P Trial Outcome Index (TOI):

__________ + __________ + __________ =________=FACT-P TOI (PWB score) (FWB score) (PCS score)

To Derive a FACT-G total score:

__________ + __________ + __________ + __________=________=FACT-G Total score (PWB score) (SWB score) (EWB score) (FWB score)

To Derive a FACT-P total score:

_________ + __________ + __________ + __________ + __________ =________=FACT-P Total score(PWB score) (SWB score) (EWB score) (FWB score) (PCS score)


PAIN P1 4 - ________ =________RELATED P2 4 - ________ =________SUBSCALE P3 4 - ________ =________(PRS) GP4 4 - ________ =________

Sum individual item scores:________ Multiply by 4: ________

Divide by number of items answered: ________=PR Subscale score

*For guidelines on handling missing data and scoring options, please refer to the Administration and ScoringGuidelines in the manual or on-line at www.facit.org.

Score range: 0-48

Score range: 0-104

Score range: 0-108

Score range: 0-156

Score range: 0-16

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