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Supplementary appendix
This appendix formed part of the original submission and has been peer reviewed.
We post it as supplied by the authors.
Supplement to: Motzer RJ, Porta C, Vogelzang NJ, et al. Dovitinib versus sorafenib
for third-line targeted treatment of patients with metastatic renal cell carcinoma:
an open-label, randomised phase 3 trial. Lancet Oncol 2014; published online
February 17. http://dx.doi.org/10.1016/S1470-2045(14)70030-0.
Motzer et al; Dovitinib versus sorafenib for third-line targeted treatment of patients with
metastatic renal cell carcinoma: an open-label, randomised phase 3 trial
Webappendix
Biomarker analysis
Longitudinal analysis of plasma biomarkers over time was carried out via a linear mixed-model analysis of
postbaseline fold-change from baseline biomarker values (log2 scale) as a function of time, treatment arm, and timeby-treatment interaction terms with a spatial exponential correlation structure on the repeated measures. The modeladjusted means (95% CI) were estimated and back-transformed to yield average fold-change from baseline of the
biomarker for a treatment group at each postbaseline time point. The P values were adjusted for multiplicity via
false discovery–rate correction.
Evaluation of plasma baseline biomarker levels and time-to-event endpoints (PFS/OS) were explored via KaplanMeier survival curves, log-rank tests, and Cox proportional hazard models. The baseline biomarkers were
dichotomized into low/high categories based on their median values at baseline (< median and ≥ median). Log-rank
tests, stratified by baseline Memorial Sloan-Kettering Cancer Center (MSKCC) risk group, for differences in
Kaplan-Meier curves between biomarker category (low/high based on </≥ median baseline values) within treatment
arms were performed. The P values were adjusted for multiplicity via a false discovery–rate correction. Median
time-to-event values (95% CI) were obtained from the Kaplan-Meier estimator, without considering baseline
MSKCC risk group as a stratification factor. Hazard ratios (95% CI) for the high vs low biomarker category within a
treatment arm were computed from Cox proportional hazard models, with biomarker category, treatment, and
biomarker-by-treatment as covariates and baseline risk assessment group as the stratification factor.
Figure legends
Appendix Figure 1. Kaplan-Meier estimates of progression-free survival investigator analysis.
Appendix Figure 2. Forest plots of progression-free survival.
MSKCC, Memorial Sloan-Kettering Cancer Center.
Appendix Figure 3. Kaplan-Meier estimates of definitive worsening of Karnofsky performance status.
Appendix Figure 4. Kaplan-Meier estimates of definitive worsening of patient-reported outcomes. A) Definitive
deterioration by 10% in the quality of life scale scores of the EORTC QLQ-C30. B) Definitive deterioration in the
FKSI-DRS score (> 4 units).
Appendix Figure 5. Kaplan-Meier estimates of progression-free survival by treatment and baseline plasma
biomarker groups.
CI, confidence interval; FGF2, fibroblast growth factor 2; HGF, hepatocyte growth factor; HR, hazard ratio; PLGF,
placental growth factor; VEGFA, vascular endothelial growth factor A. Low biomarker is defined as < median, and
high biomarker is defined as ≥ median.
Appendix Figure 6. Model-adjusted average fold-change from baseline ± 1 standard error.
FGF2, fibroblast growth factor 2; HGF, hepatocyte growth factor; HR, hazard ratio; PLGF, placental growth factor;
VEGFA, vascular endothelial growth factor A. Low biomarker is defined as < median, and high biomarker is
defined as ≥ median. P values are adjusted for the false-discovery rate. *0•05 ≥ P > 0•01. **P ≤ 0•01 (change from
baseline). #P ≤ 0•05 (dovitinib to sorafenib).
1 Appendix Table 1: Clinical trial sites
Site
Wojskowy Instytut Medyczny, Warszawa, Poland
Fodazione IRCCS Policlinico S. Matteo Univ. degli Studi Pavia, Pavia, Itlay
Klinika Nowotworów Układu Moczowego Centrum Onkologii Instytut, Warszawa, Poland
B.C. Cancer Agency, Vancouver, British Colombia, Canada
Memorial Sloan Kettering Cancer Center, NY, NY, US
Institut Gustave Roussy, Villejuif Cedex, France
Hospital general de Asturias, Oviedo, Spain
Fakultni Nemocnice Olomouc, Olomouc, Czech Republic
Sunnybrook Health Sciences Center, Toronto, Ontario, Canada
Severance Hospital, Seoul, Republic of Korea
Ist. Scien. Romagnolo per lo Studio e la Cura dei Tumori-IRST, Meldola, Italy
Austin Health, Heidelberg, Australia
Asan Medical Center, Seoul, Republic of Korea
Kliniken der Med. Hochschule Hannover, Hannover, Germany
Southampton General Hospital, Southampton, UK
Haem & Oncology Clinics of Australasia, Mater Medical Centre, South Brisbane Australia
Presidio Ospedaliero Area Aretina Nord S. Donato, Arezzo, Italy
Praxis Dr. Kube, Chemnitz, Germany
St. Joseph's Hospital, Hamilton, Ontario, Canada
General Hospital of Athens Alexandra, Athens, Greece
Westmead Hospital, Westmead, Australia
Orszagos Onkologiai Intezet, Budapest, Hungary
Hospital Clinico San Carlos, Madrid, Spain
London Regional Cancer Centre, London, Ontario, Canada
Cross Cancer Institute, Edmonton, Alberta, Canada
Hopital Europeen Georges Pompidou, Paris, France
Rabin Medical Center, Petach Tikva, Israel
Hôpital Saint André, Bordeaux Cedex, France
Hopital Minjoz, Besancon Cedex, France
Medical University of South Carolina, Charleston, SC, US
Centre Alexis Vautrin, Vandoeuvre-Les-Nancy Cedex, France
Gasthuisberg University Hospital, Leuven, Belgium
The Christie Hospital, Manchester, UK
A.O. Univ. Policl. di Modena Univ. Studi Modena e R.Emilia, Modena, Italy
Norrlands Universitetssjukhus, Umeå, Sweden
The Ottawa Hospital, Ottawa, Ontario, Canada
Azienda Ospedaliera S. Camillo-Forlanini, Roma, Italy
University of California at Los Angeles, Los Angeles, CA, US
Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli, Napoli, Italy
Fondazione IRCCS - Istituto Nazionale dei Tumori, Milano, Italy
Deke Slayton Cancer Center, Webster, TX, US
Masarykuv onkologicky institut, Brno, Czech Republic
Narodny Onkologicky Ustav, Bratislava, Slovakia (Slovak Republic)
The Queen Elizabeth Hospital, Woodville, Australia
Euromedica General Clinic of Thessaloniki, Thessaloniki, Greece
Comprehensive Cancer Centers of Nevada, Las Vegas, NV, US
Istituti Ospitalieri di Cremona, Cremona, Italy
Seoul National University Hospital, Seoul, Republic of Korea
Universitair Ziekenhuis Gent, Gent, Belgium
Chiba Cancer Center, Chiba, Japan
Institut de Cancérologie de la Loire, Saint Priest en Jarez Cedex, France
Bristol Haematology and Oncology Centre, Bristol, UK
Hospital São Lucas da PUC-RS, Porto Alegre, Brazil
Univ.-Klinikum Heidelberg, Heidelberg, Germany
Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany
Kantonsspital St. Gallen, St. Gallen, Switzerland
Hospital Vall D'Hebron, Barcelona, Spain
Hospital 12 De Octubre, Madrid, Spain
Amphia Ziekenhuis, Breda, Netherlands
Erasmus Medisch Centrum (Daniel Den Hoed Kliniek), Rotterdam, Netherlands
Royal Free Hospital, Renal Cancer Clinical Trials Unit, London, UK
Kinki University Hospital, OsakaSayama, Japan
Samsung Medical Center, Seoul, Republic of Korea
Debreceni Egyetem, Orvos es Egeszsegtudomanyi Centrum, Debrecen, Hungary
2 Principal Investigator
Cezary Szczylik
Camillo Porta
Jakub Zolnierek
Christian Kollmannsberger
Robert Motzer
Bernard Escudier
Emilio Esteban
Bohuslav Melichar
Georg A. Bjarnason
Sun Young Rha
Ugo De Giorgi
Ian D. Davis
Jaelyun Lee
Viktor Gruenwald
Matthew Wheater
Paul Mainwaring
Sergio Bracarda
Ulrich Kube
Anil Kapoor
Aristotelis Bamias
Howard Gurney
Istvan Bodrogi
José Luis González Larriba
Mary MacKenzie
Scott North
Stephane Oudard
Viktoria Neiman
Alain Ravaud
Antoine Thiery-Vuillemin
Harry Drabkin
Lionel Geoffrois
Patrick Schoffski
Robert Hawkins
Roberto Sabbatini
Camilla Thellenberg
Christina Canil
Cora Sternberg
Fairooz Kabbinavar
Giacomo Cartenì
Giuseppe Procopio
Guru Sonpavde
Ivo Kocak
Jozef Mardiak
Ken Pittman
Konstantinos Papazisis
Nicholas Vogelzang
Rodolfo Passalacqua
Sehoon Lee
Sylvie Rottey
Tekeshi Ueda
Aline Guillot
Amit Bahl
Carlos Henrique Barrios
Carsten Gruellich
Christian Eichelberg
Christian Rothermundt
Cristina Suarez Rodriguez
Daniel Castellano
O.J.L. Loosveld
W.H.J. Kruit
Ekaterini Boleti
Hirotsugu Uemura
Ho Yeong Lim
János Szántό
Patients Enrolled
16
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3
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3
3
Centre Antoine Lacassagne, Nice Cedex 2, France
Highlands Oncology Group, Fayetteville, AR, US
Pécsi Tudományegyetem, Onkotherápiás Intézet, PECS, Hungary
Centro Oncologico de Rosario, Rosario, Argentina
Kobe University Hospital, Kobe, Japan
Osaka University Hospital, Suita-city, Japan
Haukeland Universitetssykehus, Bergen, Norway
Mount Vernon Hospital, Northwood, UK
Les Urologues Associés du CHUM, Montreal, Quebec, Canada
St. Luke's Hospital and Health Network, Bethlehem, PA, US
Saskatoon Cancer Centre, Saskatoon, Saskatchewan, Canada
Centre Léon Bérard, Lyon Cedex, France
Hopital Pitie Salpetriere, Paris Cedex 13, France
Baylor College of Medicine, Dallas, TX, US
JNSZ Megyei Hetenyi Geza Korhaz-Rendelointezet, Szolnok, Hungary
Siriraj Hospital, Bangkok, Thailand
Jewish General Hospital, Montreal, Quebec, Canada
Hospital Universitario Germans Trias I Pujol, Badalona, Spain
Universitatsklinikum Ulm, Ulm, German
University of Minnesota Medical Center - Fairview, Minneapolis, MN, US
Hopital de Hautepierre, Strasbourg Cedex, France
Institut Claudius Regaud, Toulouse Cedex 3, France
Centre Hospitalière Universitaire Sart Tilman, Liège, Belgium
Hôpital Foch, Suresnes Cedex, France
University of Virginia Health Systems, Charlottesville, VA, US
CHUM - Hopital Notre-Dame, Montreal, Quebec, Canada
Academisch Ziekenhuis Maastricht, Maastricht, Netherlands
Hospital Reina Sofia, Cordoba, Spain
Corporacio Sanitaria Parc Tauli Sabadell
Centre René Gauducheau, Saint Herblain Cedex, France
University Hospital, Kyoto Prefectural Univ. of Medicine, Kyoto, Japan
Nippon Medical School Hospital, Bunkyo-ku, Japan
Texas Oncology, P.A., Houston , TX, US
Institut Paoli Calmettes, Marseille, France
Vanderbilt University Medical Center, Nashville, TN, US
Semmelweis University, Budapest Urology Clinic, Budapest, Hungary
Princess Margaret Hospital, Toronto, Ontario, Canada
Hospital Gregorio Marañon, Madrid, Spain
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Fakultni Nemocnice V Motole, Praha 5, Czech Republic
SOTIRIA General Hospital, Athens, Greece
St George's Hospital, London, UK
QE II Health Sciences Centre, Halifax, Nova Scotia, Canada
Hospital Virgen de la Victoria, Malaga, Spain
Klinikum Nuernberg Nord, Nuernberg, Germany
IRCC - Fondazione del Piemonte per l'Oncologia Univ. Torino, Candiolo, Italy
Saitama Medical University International Medical Center, Hidaka, Japan
Royal North Shore Hospital, St. Leonards, Australia
Complejo Hospitalario de Navarra, Pamplona, Spain
University of Kansas Cancer Center, Westwood, KS, US
The Chaim Sheba Medical Center, Ramat Gan, Israel
Western Hospital, Footscray, Australia
Humboldt-Univ. Charité Campus Mitte, Berlin, Germany
Kanagawa Cancer Center, Yokohama, Japan
Toranomon Hospital, Minato-ku, Japan
Wayne State University/Karmanos Cancer Institute, Detroit, MI, US
Utah Cancer Specialists, Salt Lake City, UT, US
Nagoya University Hospital, Nagoya-city, Japan
Hiroshima University Hospital, Hiroshima, Japan
Rocky Mountain Cancer Centers, Denver, CO, US
Univ.-Klinikum Leipzig, Leipzig, Germany
Hokkaido P.W.F.A.C Obihiro-Kosei General Hospital, Obihiro, Japan
Assaf Harofeh Medical Center, Zrifin, Israel
Hospital Clinic I Provincial De Barcelona, Barcelona, Spain
The West Clinic, Memphis, TN, US
Centre Eugène Marquis, Rennes Cedex, France
3 Jean-Marc Ferrero
Joseph Beck
Laszlo Mangel
Luis Fein
Masato Fujisawa
Norio Nonomura
Oddbjorn Straume
Paul Nathan
Pierre I. Karakiewicz
Sanjiv Agarwala
Sunil Yadav
Sylvie Negrier
Thibault de la Motte Rouge
Thomas Hutson
Tibor Csoszi
Vichien Srimuninnimit
Wilson Miller
Albert Font Pous
Andres Schrader
Arkadiusz Dudek
Brigitte Duclos
Christine Chevreau
Christine Gennigens
Christine Theodore
Christopher Thomas
Denis Soulieres
P.M.M.B Soetekouw
Enrique Aranda Aguilar
Enrique Gallardo Diaz
Frederic Rolland
Fumiya Hongo
Go Kimura
Gurjyot Doshi
Gwenaelle Gravis
Igor Puzanov
Imre Romics
Jennifer Knox
Jose Angel Arranz
Jose Pablo Maroto Rey
Katerina Kubackova
Konstantinos Syrigos
Lisa Pickering
Lori Wood
María Isabel Sáez Medina
Martin Wilhelm
Massimo Aglietta
Munehisa Ueno
Nick Pavlakis
Nuria Lainez
Peter Van Veldhuizen
Raanan Berger
Shirley Wong
Steffen Weikert
Takeshi Kishida
Toshimi Takano
Ulka Vaishampayan
W. Graydon Harker
Yasushi Yoshino
Akio Matsubara
Allen Cohn
Anja Dietel
Ataru Sazawa
Avishay Sella
Begona Mellado Gonzalez
Bradley Somer
Brigitte Laguerre
3
3
3
3
3
3
3
3
3
3
3
3
3
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3
2
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2
2
2
2
2
2
2
2
2
2
2
2
1
1
1
1
1
1
1
1
Tom Baker Cancer Centre, Calgary, Alberta, Canada
Univ.-Klinikum Münster, Muenster, Germany
Hospital Nuestra Senora De Valme, Dos Hermanas, Spain
Centre Francois Baclesse, Caen Cedex, France
Hospital Durans I Reynals-ICO, Hospitalet de Llobregat, Spain
University of California San Diego, La Jolla, CA, US
Allgem. oeffentl. Krankenhaus der Stadt Linz, Linz, Austria
Sanatorio de la Providencia, Buenos Aires, Argentina
Straub Clinic & Hospital, Honolulu, HI, US
Yokohama Minami Kyousai Hospital, Yokohama-city, Japan
University of Texas Southwestern Medical Center, Dallas, TX, US
Cliniques Universitaires Saint-Luc, Bruxelles, Belgium
Kaiser Permanente Hawaii, Honolulu, HI, US
Hospital Fundacion Alcorcón, Alcorcón, Spain
Hospital del Mar, Barcelona, Spain
Saludcoop, Bogota, Colombia
Hospital Clinica Benidorm, Benidorm, Spain
Kyushu University Hospital, Fukuoka-city, Japan
Tokyo Women's Medical University Hospital, Shinjuku, Japan
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
Rockwood Clinic, Spokane, WA, US
Gemeinschaftspraxis Dr. Klausmann/Dr. Welslau, Aschaffenburg, Germany
Univ.Klinik für Innere Medzin I, Wien, Austria
Friedrich-Schiller-Universität Jena, Jena, Germany
Hopital Albert Michallon, Grenoble cedex, France
Willamette Valley Clinical Studies, Springfield, OR, US
Instituto Valenciano de Oncologia (I.V.O), Valencia, Spain
Keio University Hospital, Shinjuku-ku, Japan
H. Universitario Insular de Gran Canaria, Las Palmas de Gran Canarias, Spain
Kobe City Medical Center General Hospital, Kobe, Japan
Ehime University Hospital, Toon-city, Japan
Ållesuns sykehus, Ålesund, Norway
Shinshu University Hospital, Matsumoto, Japan
Universitätsklinikum Erlangen-Nürnberg, Erlangen, Germany
Universitätsklinikum Giessen und Marburg GmbH, Marburg, Germany
Northeast Georgia Cancer Care, Athens, GA, US
Leiden University Medical Cente, Leiden, Netherlands
Hospital Clinico Universitario Santiago De Compostela, Santiago de Compostela, Spain
Cedars Sinai Medical Center, Los Angeles, CA, US
CINJ at Cooper University Hospital, Voorhes, NJ, US
Osaka City University Hospital, Osaka-city, Japan
King Faisal Specialist Hospital & Research Center Riyadh, Riyadh, Saudi Arabia
Cancer Institute Hospital of JFCR, Koto, Japan
The Leicester Royal Infirmary, Leicester, UK
Osaka Medical College Hospital, Takatsuki, Japan
Klinikum Weiden, Weiden, Germany
Karolinska Universitetssjukhuset Solna, Stockholm, Sweden
Univ.-Klinikum Greifswald, Greifswald, Germany
Albert Schweitzer Ziekenhuis, Dordrecht, Netherlands
VU Medisch Centrum, Amsterdam, Netherlands
Florida Cancer Specialists, Fort Myers, FL, US
Yamagata University Hospital, Yamagata, Japan
Saitama Cancer Center Hospital, Kitaadachi-gun, Japan
4 Daniel Heng
Edwin Herrmann
Eva Maria Fernandez Parra
Florence Joly
Francisco Javier Garcia del
Muro Solans
Frederick Millard
Frens Krause
Guillermo Lerzo
Ian Okazaki
Ichiro Ikeda
James Brugarolas
Jean-Pascal Machiels
Jennifer Carney
Jesus García-Donas
Joaquim Bellmunt Molins
Jose Lobatón
Jose Manuel Cervera
Katsunori Tatsugami
Kazunari Tanabe
Kazuo Nishimura
Kirk Lund
Manfred Welslau
Manuela Schmidinger
Marc-Oliver Grimm
Mathieu Laramas
Michael Monticelli
Miguel Angel Climent
Duran
Mototsugu Oya
Adolfo Murias Rosales
Mutsushi Kawakita
Nozomu Tanji
Olbjorn Klepp
Osamu Ishizuka
Peter Goebell
Peter Olbert
Petros Nikolinakos
S. Osanto
Rafael Lopez Lopez
Robert Figlin
Robert Somer
Satoshi Tamada
Shouki Bazarbashi
Shunji Takahashi
Steve Nicholson
Teruo Inamoto
Theordor Klotz
Ulrika Harmenberg
Uwe Zimmermann
Van den Bosch, dr. J.
A.J.M. van den Eertwegh
Waide Weaver
Yoshihiko Tomita
Yukio Kageyama
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Supplemental Figure 1.
n/N
Probability event free (%)
100
Dovitinib
Sorafenib
80
Median, months Hazard Ratio
(95% CI)
(95% CI)
3·9 (3·7-5·1)
1·00 (0·82-1·21)
3·9 (3·7-5·0)
212/284
214/286
60
40
20
0
0
3
6
9
12
15
18
21
Months
Patients at risk
Dovitinib
284
169
56
30
5
1
0
0
Sorafenib
286
177
59
24
6
2
0
0
Supplemental Figure 2.
n
All patients
570
Favors dovitinib Favors sorafenib
Karnofsky performance
< 90
220
≥ 90
350
Region
Asia Pacific and Japan
96
Americas
133
Europe and Middle East
341
MSKCC risk group
Favorable
117
Intermediate
326
Poor
127
Age
< 65 years
352
≥ 65 years
218
Sex
Male
432
Female
138
0 ·4
0 ·6
0 ·8
1
1·2
1·4
1·6
Supplemental Figure 3.
Probability event free (%)
100
n/N
80
Dovitinib
Sorafenib
60
Median, months Hazard Ratio
(95% CI)
(95% CI)
5·1 (3·8-6·5)
1·12 (0·87-1·45)
5·7 (4·6-7·4)
120/284
115/286
40
20
0
0
3
6
9
12
15
18
21
1
2
1
0
0
0
Months
Patients at risk
Dovitinib
Sorafenib
284
286
117
128
49
58
20
17
7
6
Supplemental Figure 4.
A
Probability event free (%)
100
n/N
Dovitinib
Sorafenib
80
152/284
148/286
Median, months Hazard Ratio
(95% CI)
(95% CI)
4·1 (3·2-5·3)
1·08 (0·86-1·36)
4·7 (3·8-5·6)
60
40
20
0
0
3
6
9
12
15
18
21
Months
Patients at risk
Dovitinib
284
123
53
21
8
1
1
0
Sorafenib
286
142
55
16
5
2
0
0
B
Probability event free (%)
100
n/N
Dovitinib
Sorafenib
80
110/284
98/286
Median, months Hazard Ratio
(95% CI)
(95% CI)
7·1 (5·4-10·2)
1·20 (0·91-1·58)
11·3 (6·5-14·3)
60
40
20
0
0
3
6
9
12
15
18
21
Months
Patients at risk
Dovitinib
284
150
62
28
9
1
1
0
Sorafenib
286
168
70
25
6
1
0
0
1·0
Sorafenib: FGF2 < median
Sorafenib: FGF2 ≥ median
Dovitinib: FGF2 < median
0·2
Progression Free Survival Probability
3·8 (3·6-5·0)
3·7 (2·4-3·8)
1·09
0·3290
Sorafenib 3·7 (3·5-3·7)
3·5 (2·2-3·7)
1·03
0·3975
10
Months
15
20
Sorafenib: HGF < median
Sorafenib: HGF ≥ median
Dovitinib: HGF < median
Median, months (95% CI)
Dovitinib: HGF ≥ median
0·8
High
biomarker
5·4 (3·8-5·7)
2·3 (2·0-3·6)
1·84
< 0·0001
Sorafenib 3·8 (3·6-4·4)
2·8 (2·0-3·6)
1·45
0·0086
0·6
Dovitinib
0·4
Cox HR
Log-rank
(High/Low) p-value
Low
biomarker
·
0·2
5
1·0
10
Months
15
20
Sorafenib: PLGF < median
Sorafenib: PLGF ≥ median
Dovitinib: PLGF < median
Median, months (95% CI)
Dovitinib: PLGF ≥ median
0·8
High
biomarker
3·8 (3·7-5·3)
3·5 (2·1-3·7)
1·20
0·1409
Sorafenib 3·7 (3·6-5·2)
3·3 (2·0-3·6)
1·47
0·0050
Dovitinib
0·4
0·2
Cox HR
Log-rank
(High/Low) p-value
Low
biomarker
0·6
0·0
Progression Free Survival Probability
Cox HR Log-rank
(High/Low) p-value
0·0
5
1·0
10
Months
15
20
Sorafenib: VEGFA < median
Sorafenib: VEGFA ≥ median
Dovitinib: VEGFA < median
Median, months (95% CI)
Dovitinib: VEGFA ≥ median
0·8
Low
biomarker
High
biomarker
Cox HR
(High/Low)
Log-rank
p-value
3·9 (3·7-5·4)
3·3 (2·0-3·7)
1·55
0·0085
Sorafenib 3·7 (3·5-3·9)
2·1 (1·9-3·6)
1·35
0·0356
0·6
Dovitinib
0·4
0·2
0·0
Progression Free Survival Probability
5
1·0
0
VEGFA
High
biomarker
Dovitinib
0·4
0
PLGF
Low
biomarker
0·6
0
HGF
Median, months (95% CI)
Dovitinib: FGF2 ≥ median
0·8
0·0
FGF2
Progression Free Survival Probability
Supplemental Figure 5.
0
5
10
Months
15
20
Dovitinib
Sorafenib
2·5
2·0
HGF
1·5
1·0
#
0·5
*
0·0
Baseline
4
Number of samples
PLGF
Mean Fold-Change From Baseline (± 1 SE)
Dovitinib 281
Sorafenib 280
3·0
9
21
Week
242 207
240 206
98
95
Dovitinib
Sorafenib
**
2·5
**
2·0
**
1·5
33
**
48
40
**
**
0·5
0·0
Number of samples
Dovitinib 265
Sorafenib 264
231 197
230 195
94
88
2·0
**
1·5
1·0
0·5
#
#
#
**
**
*
33
VEGFA
3·0
4
9
21
Week
235 202
235 203
95
91
#
33
45
44
39
19
11
Dovitinib
2·5
2·0
**
**
**
**
**
*
**
1·5
**
1·0
*
0·5
0·0
Baseline
45
19
11
#
Sorafenib
Number of samples
47
39
**
**
0·0
Dovitinib 281
Sorafenib 279
**
**
9
21
Week
2·5
Baseline
19
11
1·0
4
Dovitinib
Sorafenib
Number of samples
**
Baseline
3·0
45
**
#
Mean Fold-Change From Baseline (± 1 SE)
3·0
Mean Fold-Change From Baseline (± 1 SE)
FGF2
Mean Fold-Change From Baseline (± 1 SE)
Supplemental Figure 6.
Dovitinib 253
Sorafenib 250
4
9
21
33
45
86
83
44
37
19
11
Week
216 184
218 185
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