1
ANEXO: Publicaciones 2018
Comunicaciones a Congresos y Manuscritos en 2018
En 2018 se han publicado 42 comunicaciones a congresos, internacionales y
nacional. Si consideramos el promotor del estudio, 19 comunicaciones son de
estudios con promotor GEICAM, 19 comunicaciones de estudios con promotor
no GEICAM, y en 4 comunicaciones no aplica al ser comunicaciones generales
no específicas de un estudio concreto.
En 2018 se han publicado 14 manuscritos, todos ellos en revistas
internacionales, siendo uno de ellos un artículo de revisión. Si consideramos el
promotor del estudio, 6 manuscritos son de estudios con promotor GEICAM y 7
de estudios con promotor no GEICAM.
LISTADO DE COMUNICACIONES A CONGRESOS
ASCO 2018 - 12 comunicaciones:
Una comunicación oral [GEICAM/2010-03 (D-CARE)],
Un poster discussion [Epi-GEICAM] y,
Diez pósteres [2 análisis conjuntos de los estudios GEICAM/2006-03 y
GEICAM/2006-14, 2 análisis conjuntos de los estudios GEICAM/2012-
08_TRIO-022 (PALOMA-2) y PALOMA-3, GEICAM 2015-06 (COMETA-Breast)
(trial in progress), GEICAM/2015-05 (POSITIVE), GEICAM/2013-07_TRIO-023
(EMBRACA), un análisis conjunto de los estudios GEICAM/2013-07_TRIO-023
(EMBRACA) y GEICAM/2014-04_TRIO-024 (ABRAZO), GEICAM/2008-04
(PHEREXA), y GEICAM/2010-11 (APHINITY)].
2
PROMOTOR
GEICAM TIPO TÍTULO Y AUTORES
SI POSTER
GEICAM/2006-03 y GEICAM/2006-14
Integrative cluster classification to predict pathological complete response to neoadjuvant
chemotherapy in early breast cancer
Alba E, Rueda OM, Lluch A, Albanell J, Chin SF, Chacón López-Muñiz JI, Calvo L, De la Haba-
Rodriguez J, Bermejo B, Ribelles N, Cirauqui B, Ramos Vázquez M, Arcusa A, Carrasco E, Herranz
J, Chiesa M, Caballero R, Santonja A, Rojo F, Caldas C
J Clin Oncol 36, 2018 (suppl; abstr 579)
https://meetinglibrary.asco.org/record/162558/abstract
SI POSTER
GEICAM/2006-03 y GEICAM/2006-14
Dynamic genomic instability modulation by neoadjuvant therapy in early breast cancer
(GEICAM/2006-03_2006-14)
Alba E, Rueda OM, Lluch A, Albanell J, Chin SF, Chacon JI, Calvo L, De La Haba J, Bermejo B,
Ribelles N, Sanchez Rovira P, Plazaola A, Barnadas A, Carrasco E, Herranz J, Chiesa M,
Caballero R, Santonja Climent A, Rojo F, Caldas C
J Clin Oncol 36, 2018 (suppl; abstr 592)
https://meetinglibrary.asco.org/record/163270/abstract
SI POSTER
TiP
GEICAM 2015-06 (COMETA-Breast)
A phase II clinical trial to analyze olaparib response in patients with BRCA1 and/or BRCA2
promoter methylation with advanced breast cancer (GEICAM/2015-06 COMETA-Breast study)
De La Haba J, Guerrero-Zotano A, Perez-Fidalgo JA, Gonzalez Santiago S, Muñoz M, Andres R,
Cruz Zambrano C, Moran Salama S, Lopez-Tarruella S, Quiroga Garcia V, Servitja S, Mele M,
Alonso Soler S, Adamo B, Escudero MJ, Martin N, Bezares S, Caballero R, Esteller M, Rojo F
J Clin Oncol 36, 2018 (suppl; abstr TPS1114)
https://meetinglibrary.asco.org/record/165354/abstract
SI POSTER
DISCUSSION
EpiGEICAM-01
Dietary inflammatory index and breast cancer risk by menopausal status and histological
subtype
Castello A, Shivappa N, Ruiz A, Casas A, Lluch Hernandez A, Baena-Cañada JM, Antolin S,
Sánchez Rovira P, Ramos Vazquez M, Garcia-Saenz JA, Anton A, Munoz M, de Juan A, Jara-
Sanchez C, Jesus Vioque, Beatriz Perez-Gomez, James R. Hébert, Virginia Lope, Miguel Martin,
Marina Pollan
J Clin Oncol 36, 2018 (suppl; abstr 1521)
https://meetinglibrary.asco.org/record/162924/abstract
NO POSTER
GEICAM/2015-05 (POSITIVE)
POSITIVE (IBCSG 48-14/BIG 8-13/A221405): Evaluating outcomes after interrupting
endocrine therapy (ET) for women with endocrine responsive (ER+) early breast cancer (BC)
who desire pregnancy
Partridge AH, Pagani O, Azim HA, Peccatori F, Ruggeri M, Regan MM, Gelber RD, Sun Z, for the
POSITIVE Steering Commitee
J Clin Oncol 36, 2018 (suppl; abstr TPS596)
https://meetinglibrary.asco.org/record/165227/abstract
3
NO POSTER
GEICAM/2013-07_TRIO-023 (EMBRACA)
EMBRACA: Efficacy outcomes in clinically relevant subgroups comparing talazoparib
(TALA), an oral poly ADP ribose polymerase (PARP) inhibitor, to physician's choice of
therapy (PCT) in patients with advanced breast cancer and a germline BRCA mutation
Rugo HS, Ettl J, Woodward NE, Hurvitz SA, Goncalves A, Lee KH, Fehrenbacher L, Yerushalmi R,
Mina LA, Martin M, Hubert Roche H, Im YH, Markova D, Tudor IC, Eiermann W, Blum JL, Hannah
AL, Keating Litton J
J Clin Oncol 36, 2018 (suppl; abstr 1069)
https://meetinglibrary.asco.org/record/160639/abstract
NO POSTER
GEICAM/2013-07_TRIO-023 (EMBRACA) y GEICAM/2014-04_TRIO-024 (ABRAZO)
Analysis of germline BRCA1/2 mutated (gBRCAmut) hormone receptor-positive (HR+) and
triple negative breast cancer (TNBC) treated with talazoparib (TALA)
Eiermann W, Rugo HS, Diab S, Ettl J, Hurvitz SA, Goncalves A, Lee KH, Fehrenbacher L,
Yerushalmi R, Mina LA, Martin M, Hubert Roche H, Im YH, Markova D, Tudor IC, Blum JL, Hannah
AL, Keating Litton J
J Clin Oncol 36, 2018 (suppl; abstr 1070)
https://meetinglibrary.asco.org/record/160640/abstract
NO POSTER
GEICAM/2008-04 (PHEREXA)
Final overall survival (OS) analysis of PHEREXA: A randomized phase III trial of trastuzumab
(H) + capecitabine (X) ± pertuzumab (P) in patients with HER2-positive metastatic breast
cancer (MBC) who experienced disease progression during or after H-based therapy
Urruticoechea A, Rizwanullah,Seock-Ah Im M, Sánchez Ruiz AC, Lang I, Tomasello G, Douthwaite
H, Badovinac Crnjevic T, Heeson S, Eng-Wong J, Munoz M
J Clin Oncol 36, 2018 (suppl; abstr 1013)
https://meetinglibrary.asco.org/record/158538/abstract
NO POSTER
GEICAM/2010-11 (APHINITY)
Patient (pt)-reported function and symptoms in APHINITY: A randomized comparison of
chemotherapy (C) + trastuzumab (H) + placebo (Pla) versus C + H + pertuzumab (P) as
adjuvant therapy in pts with HER2-positive early breast cancer (EBC)
Baselga J, Petersen JA, Clark E, Barton C, Restuccia E, Procter MJ, Sonnenblick A, Fumagalli D,
Parlier D, Arahmani A, Viale G, Reaby LL, Frank E, Gelber RD, Piccart-Gebhart MJ, Bines J, von
Minckwitz G, McGarrahan Gasper S
J Clin Oncol 36, 2018 (suppl; abstr 521)
https://meetinglibrary.asco.org/record/162838/abstract
NO POSTER
GEICAM/2012-08_TRIO-022 (PALOMA2) y PALOMA3
Hematologic adverse events following palbociclib (PAL) dose reduction in patients (pts) with
hormone receptor‒positive (HR+)/human epidermal growth factor receptor 2‒negative
(HER2‒) advanced breast cancer (ABC): Pooled analysis from randomized phase 2 and 3
studies
Verma S, Im SA, Ro J, Bondarenko I, Masuda N, Colleoni M, Verma S, Schnell P, Bananis E, Lu
DR, Ettl J, Cristofanilli M, Rugo HS, Finn RS
J Clin Oncol 36, 2018 (suppl; abstr 1060)
https://meetinglibrary.asco.org/record/161827/abstract
NO POSTER
GEICAM/2012-08_TRIO-022 (PALOMA2) y PALOMA3
Treatment effect of palbociclib (PAL) plus endocrine therapy (ET) by prognostic and intrinsic
subtype: A joint analysis of PALOMA2 and PALOMA3
4
Finn RS, Cristofanilli M, Ettl J, Gelmon KA, Verma S, Colleoni M, Giorgetti C, Roland Gauthier E,
Liu Y, Lu DR, Huang Bartlett C, Slamon DJ, Turner NC, Rugo HS
J Clin Oncol 36, 2018 (suppl; abstr 1023)
https://meetinglibrary.asco.org/record/160635/abstract
NO ORAL
GEICAM/2010-03 (D-CARE)
Adjuvant denosumab in early breast cancer: First results from the international multicenter
randomized phase III placebo controlled D-CARE study
Coleman RE, Finkelstein D, Barrios CH, Martin M, Iwata H, Glaspy JA, Zhou Y, Jandial D, Chan A
J Clin Oncol 36, 2018 (suppl; abstr 501)
https://meetinglibrary.asco.org/record/160258/abstract
SEOM 2018 - 6 comunicaciones:
Cinco presentaciones orales (una de ellas en la sesión plenaria) [(2 análisis
conjuntos de los estudios GEICAM/2006-03 y GEICAM/2006-14),
GEICAM/2011-04 (BRECOL), EpiGEICAM-01, GEICAM/2014-05 (BLISSAFE)]
y,
Un póster destacado [GEICAM/2013-02 (PEARL)].
PROMOTOR
GEICAM TIPO TÍTULO Y AUTORES
SI
ORAL
SESIÓN
PLENARIA
GEICAM/2006-03 y GEICAM/2006-14
La clasificación en “integrative clusters” del cáncer de mama predice la
respuesta patológica completa a quimioterapia neoadyuvante
Alba E, Lluch A, Albanell J, Chacón López Muñiz J.I., Calvo L, de la Haba
Rodríguez J, Santonja A, Chiesa M, Rojo F, Caldas C
Sesión Plenaria PLE-3
SI ORAL
GEICAM/2011-04 (BRECOL)
Perfil epigenético en pacientes oncológicos con modificación de la presión
arterial secundaria a tratamiento con anti-VEGF
de la Haba J, Morales Ruiz T, García Alfonso P, Ponce Lorenzo J, Calvo L, Antón A,
García Ortiz MV, Martín N, Gallego J, Rodríguez Lescure
O-18 (sesión de comunicaciones de cáncer de mama avanzado)
5
SI ORAL
GEICAM/2006-03 y GEICAM/2006-14
Modulación dinámica de la inestabilidad genómica por terapia neoadyuvante
en cáncer de mama precoz
Alba E, Lluch A, Albanell J, Chacón López Muñiz J.I., Calvo L, de la Haba Rodriguez
J, Sánchez Rovira P, Chiesa M, Rojo F, Caldas C
O-4 (sesión de comunicaciones de cáncer de mama precoz)
SI ORAL
EpiGEICAM-01
Sobrealimentación y riesgo de cáncer de mama por subtipo histológico en el
estudio EpiGEICAM
Pollan M, Lope V, Ruiz A, Casas AM, Baena Cañada JM, Antolin S, Ramos
Vázquez M, Garcia Saenz JA, Bezares S, Martín M
O-10 (sesión de comunicaciones de cáncer hereditario y prevención)
NO ORAL
GEICAM/2014-05 (BLISSAFE)
Aplicación del gel vaginal de estriol 0,005% en mujeres postmenopáusicas
con cáncer de mama en estadio precoz y receptores hormonales positivos, en
tratamiento adyuvante con inhibidores de la aromatasa, estudio fase II,
prospectivo, aleatorizado, doble ciego y controlado con placebo: estudio
BLISSAFE
Sánchez Rovira P, Linden Hirschberg A, Gil Gil M, Antolín Novoa S, García Estévez
L, Bermejo de las Heras B, Sánchez Vigil de la Villa I, Suárez Almarza J, Palma
Santisteban M , Nieto Magro C
O-1 (sesión de comunicaciones de cáncer de mama precoz)
SI POSTER
DESTACADO
GEICAM/2013-02 (PEARL)
Evaluación de las posibles interacciones farmacológicas entre Palbociclib y
Exemestano - Resultados del subestudio farmacocinético del ensayo PEARL
(GEICAM/2013-02)
Gil-Gil M, Hoffman J, Ruiz-Borrego M, Muñoz M, Calvo L, Crownover P, García-
Sáenz JA, Alba E, Martín N, Martín M
P. DEST-4
ESMO CONGRESS 2018 – 9 comunicaciones:
Ocho pósteres [EpiGEICAM-01, GEICAM/2012-08_TRIO-022 (PALOMA2): 2 análisis
conjuntos con otros estudios, GEICAM/2013-07_TRIO-023 (EMBRACA) y
GEICAM/2014-04_TRIO-024 (ABRAZO) ].
Una comunicación oral [GEICAM/2013-07_TRIO-023 (EMBRACA)].
6
PROMOTOR
GEICAM TIPO TÍTULO Y AUTORES
SI POSTER
EpiGEICAM-01
Psychological distress and health-related quality of life in women recently
diagnosed with breast cancer
Fernández de Larrea N, Pérez Gómez B, Ruiz A, Casas AM, Bermejo B, Baena
Cañada JM, Antolin S, Sánchez Rovira P, Ramos Vázquez M, Garcia Saénz JA, Antón
A, Muñoz M, Jara Sánchez C, Moreno F, Adrover E, Oltra A, Brunet J, Bezares S,
Martín M, Pollán M
Abstract 268P: Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018,
mdy270.262,
https://doi.org/10.1093/annonc/mdy270.262
NO POSTER
GEICAM/2012-08_TRIO-022 (PALOMA2)
First-line treatment for endocrine sensitive bone-only metastatic breast cancer:
is more always better? (Studies SWOG, FACT, FALCON, MONALEESA2,
MONALEESA7, MONARCH3 AND PALOMA2)
Toss A, Venturelli M, Sperduti I, Isca C, Barbieri E, Piacentini F, Omarini C, Cortesi L,
Cascinu S, Moscetti L
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy272.327
https://doi.org/10.1093/annonc/mdy272.327
NO POSTER
GEICAM/2012-08_TRIO-022 (PALOMA2)
Progression Free Survival (PFS) Benefit from First line Endocrine Based
Therapies in Postmenopausal Women with HR+ HER2- Metastatic Breast Cancer
(MBC) according to different Prognostic Subgroups: A Combined Analysis of
Data from PALOMA 2, MONALEESA 2, MONARCH 3, FALCON, SWOG and FACT
Trials
Rossi V, Giannarelli D, Berchialla P, Nisticò C, Ferretti G, Gasparro S, Malaguti P,
Russillo M, Catania G, Vigna L, Mancusi RL, Cognetti F, Fabi A
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy272.330
https://doi.org/10.1093/annonc/mdy272.330
NO POSTER
PRP-001, PRP-002, GEICAM/2013-07_TRIO-023 (EMBRACA) Y GEICAM/2014-
04_TRIO-024 (ABRAZO)
Population pharmacokinetic analyses for talazoparib (TALA) in cancer patients
Yu Y, Durairaj C, Shi H, Wang DD
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy279.419
https://doi.org/10.1093/annonc/mdy279.419
NO POSTER
GEICAM/2013-07_TRIO-023 (EMBRACA) Y GEICAM/2014-04_TRIO-024 (ABRAZO)
Exposure-safety analyses in breast cancer patients with germline BRCA1/2
mutations receiving talazoparib (TALA) in EMBRACA and ABRAZO trials
Elmeliegy M, Yu Y, Litton JK, Turner NC, Czibere A, Wilson GG, Tudor IC, Zheng J,
Wang DD
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy272.296
https://doi.org/10.1093/annonc/mdy272.296
7
NO POSTER
GEICAM/2013-07_TRIO023 (EMBRACA)
Exposure-efficacy progression-free survival (PFS) analyses of breast cancer
patients with germline BRCA1/2 mutations receiving talazoparib in the phase 3
EMBRACA trial
Yu Y, Elmeliegy M, Litton JK, Tudor IC, Czibere A, Zheng J, Wang DD
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy272.295
https://doi.org/10.1093/annonc/mdy272.295
NO POSTER
GEICAM/2013-07_TRIO023 (EMBRACA)
EMBRACA: Efficacy and safety in comparing talazoparib (TALA) with physician's
choice of therapy (PCT) in patients (pts) with advanced breast cancer (aBC) and
a germline BRCA mutation (gBRCAm); BRCA1/BRCA2 subgroup analysis
Gonçalves A, Eiermann W, Rugo HS, Ettl J, Hurvitz SA, Yerushalmi R, Martín M, Al-
Adhami M, Tudor IC, Blum JL, Hannah AL, Litton JK
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy272.294
https://doi.org/10.1093/annonc/mdy272.294
NO POSTER
GEICAM/2013-07_TRIO023 (EMBRACA)
EMBRACA: Comparison of efficacy and safety of talazoparib (TALA) and
physician's choice of therapy (PCT) in patients (pts) with advanced breast
cancer (aBC), a germline BRCA1/2 mutation (gBRCAm), and prior platinum
treatment
Martín M, Eiermann W, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Yerushalmi R,
Markova D, Tudor IC, Blum JL, Hannah AL, Litton JK
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy272.293
https://doi.org/10.1093/annonc/mdy272.293
NO ORAL
GEICAM/2013-07_TRIO023 (EMBRACA)
Patient-reported outcomes (PRO) in patients (pts) with advanced breast cancer
and a germline BRCA1/2 mutation (gBRCAm) receiving talazoparib (TALA) vs
physician’s choice chemotherapy treatment (PCT): a focus on the EMBRACA
triple negative (TNBC) subpopulation
Rugo HS, Quek R, Ettl J, Hurvitz SA, Bhattacharyya H, Hannah AL, Litton JK
Annals of Oncology, Volume 29, Issue suppl_8, 1 October 2018, mdy272.284
https://doi.org/10.1093/annonc/mdy272.284
CONGRESO DE LA SOCIEDAD ESPAÑOLA DE EPIDEMIOLOGÍA – 1
comunicación:
Un póster [EpiGEICAM-01].
8
PROMOTOR
GEICAM TIPO TÍTULO Y AUTORES
SI POSTER
EpiGEICAM-01
Personality traits and health related quality of life
Fernández de Larrea N, Pérez Gómez B, Gavilá J, Casas A.M, Baena Cañada JM,
Antolín S, Bezares S, Martín M, Pollán M; on behalf of GEICAM
Número de póster: C-830
IX CONGRESO NACIONAL DE BIOBANCOS 2018: Trabajando el presente
para la investigación del futuro, un tesoro por descubrir – 4
comunicaciones:
Cuatro pósteres (no relacionados con un estudio específico).
PROMOTOR
GEICAM TIPO TÍTULO Y AUTORES
NO APLICA PÓSTER
Evaluación de los cambios en la calidad de muestras de ARN de tejido
tumoral parafinado almacenadas a -80ºC tras cinco ciclos de
congelación-descongelación
Méndez O. Mª., Chamizo C, Zazo S, García A. Mª, Lázaro S, Carrasco A,
Caballero R, Almeida M
P13
NO APLICA PÓSTER
Diseño de un protocolo de recogida de muestras biológicas para el
análisis del microbioma en pacientes oncológicos en el contexto de un
estudio clínico multicéntrico
García AM, Méndez OM, Carrasco A, Lázaro S, Caballero R, Almeida M
P30
9
NO APLICA PÓSTER
(SPEED)
Calidad en la gestión de la información asociada a las muestras
biológicas en el marco de un biobanco de colecciones remanentes de
ensayos clínicos
Almeida M, Caro R, Méndez O. Mª, García A. Mª, Lázaro S, Carrasco A,
Caballero R
SP03
NO APLICA PÓSTER
Avances del proyecto OPTIMARK
Artiga MJ, Aguilar R, Almeida M, Almenara I, Astudillo A, Bahamonde O,
Belar O, Bermudo R, Campos Y, Castro E, Concha A, DeLaPuente R,
Escalante M, Escámez T, Esteva-Socias M, Fraga M, Garcia-Molina E,
Gómez E, Guerrero C, Jauregui L, Iglesias M, Isidro P, Martín-Arruti M,
Novoa I, Peiró-Chova L, Rábano A, Rebolledo A.B, Ruíz Miró M, Serrate A,
Torá M, Vieiro P, Villar V, Villena C, Zazo S, Rejón JD
P03
ESMMO IMMUNO-ONCOLOGY CONGRESS 2018 – 1 comunicación:
Un póster [GEICAM/2015-04 (PANGEA-Breast)].
PROMOTOR
GEICAM TIPO TÍTULO Y AUTORES
SI PÓSTER
GEICAM/2015-04 (PANGEA-Breast)
Run-in-phase results from a multicenter phase II trial to evaluate
pembrolizumab (P) and gemcitabine (Gem) in patients (pts) with HER2-
negative advanced breast cancer (ABC): GEICAM/2015-04 PANGEA-
Breast
Quiroga V, Holgado E, Alonso J.L, Andres R, Moreno Anton F, Alamo De La
Gala MDC, Henao F, Cirauqui Cirauqui B, Margeli M, Cortes Castan J, Gion
Cortes M, Soto A, Benito S, Escudero MJ, Chiesa M, Caballero R, Bezares
Montes S, Carrasco E.M, De La Cruz Merino L
Annals of Oncology, Volume 29, Issue suppl_10, 1 December 2018,
mdy487.019
https://oncologypro.esmo.org/Meeting-Resources/ESMO-Immuno-Oncology-
Congress-2018/Run-in-phase-results-from-a-multicenter-phase-II-trial-to-
evaluate-pembrolizumab-P-and-gemcitabine-Gem-in-patients-pts-with-
HER2-negative-advanced-breast-cancer-ABC-GEICAM-2015-04-PANGEA-
Breast
10
SABCS 2018 – 8 comunicaciones:
Una comunicación oral [CIBOMA/2004-01_GEICAM/2003-11 Study].
Un póster discussion [GEICAM/2009-03 (ConvertHER Study)].
Seis pósteres [(Análisis conjunto de los estudios GEICAM/9906,
GEICAM/2003-02, ABCSG6, ABCSG8 y TransATAC), (Análisis conjunto de los
estudios GEICAM/2012-09 y CIBOMA/2004-01_GEICAM/2003-11),
(GEICAM/2017-08 (PANTHERA Study), (Análisis conjunto de los estudios
GEICAM/2006-03 y GEICAM/2006-14), (GEICAM/2006-11 (LEA Study)), y
(GEICAM/2015-05 (POSITIVE Study)].
PROMOTOR
GEICAM TIPO TÍTULO Y AUTORES
SI ORAL
CIBOMA/2004-01_GEICAM/2003-11
Efficacy results from CIBOMA/2004-01_GEICAM/2003-11 study: a randomized
phase III trial assessing adjuvant capecitabine after standard chemotherapy for
patients with early triple negative breast cancer
Martín M, Barrios C.H, Torrecillas L, Ruiz-Borrego M, Bines J, Segalla J, Ruiz A,
García-Sáenz JA, Torres R, de la Haba J, García E, Gómez HL, Llombart A, Rodríguez
de la Borbolla M, Baena JM, Barnadas A, Calvo L, Pérez-Michel L, Ramos M,
Castellanos J, Rodríguez-Lescure A, Cárdenas J, Vinholes J, Martínez de Dueñas E,
Godes M.J, Seguí MA, Antón A, López-Álvarez P, Moncayo J, Amorim G, Villar E,
Reyes S, Sampaio C, Cardemil B, Escudero M.J, Bezares S, Carrasco E, Lluch A, on
behalf of CIBOMA (Iberoamerican Coalition for Research in Breast Oncology), LACOG
(Latin American Cooperative Oncology Group) and GEICAM Spanish Breast Cancer
Group
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr GS2-04.
http://cancerres.aacrjournals.org/content/79/4_Supplement/GS2-04
SI POSTER
DISCUSSION
GEICAM/2009-03 (ConvertHER)
FGFR4 as a master regulator of HER2E subtype in the primary and metastatic
setting
Garcia-Recio S, Parker JS, Prat A, Fan C, Mott K, and Perou CM
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr PD9-04.
http://cancerres.aacrjournals.org/content/79/4_Supplement/PD9-04
SI POSTER
GEICAM/9906, GEICAM/2003-02, ABCSG6, ABCSG8 y TransATAC
Prediction of Distant Recurrence by EndoPredict in Patients with Estrogen
Receptor-Positive, HER2-Negative Breast Cancer who Received Adjuvant
Endocrine Therapy plus Chemotherapy (ET+C) or Endocrine Therapy Alone (ET)
Sestak I/Martín M (joined first authors), Dubsky P, Rojo F, Cuzick J, Filipits M, Ruiz A,
Buus R, Hlauschek D, Rodríguez-Lescure A, Dowsett M, Gnant M
11
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr P2-08-04.
http://cancerres.aacrjournals.org/content/79/4_Supplement/P2-08-04
SI POSTER
GEICAM/2012-09 y CIBOMA/2004-01_GEICAM/2003-11
Standardized nCounter-based determination of estrogen receptor (ER),
progesterone receptor (PR) and HER2 receptor status in breast cancer
Pascual T, Tsai Y.S, Martin M, Lluch A, Cortes J, Llombart A, Conte PF, Guarneri V,
Rimawi MF, Alba E, Adamo B, Vidal M, Pare L, Muñoz M, Galvan P, Gonzalez-Farre
B, Brauer HA, Sullivan A, Nuciforo P, Parker JS, Prat A
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr P2-08-06.
http://cancerres.aacrjournals.org/content/79/4_Supplement/P2-08-06
NO POSTER
GEICAM/2017-08 (PANTHERA)
Phase Ib clinical trial of coPANlisib in combination with Trastuzumab emtansine
(T-DM1) in pretreated unresectable locally advanced or metastatic HER2-positive
breAst cancer “Panthera”
Hassan A, Gullo G, O'Reilly S, Ruiz-Borrego M, Toomey S, Grogan L, Breathnach O,
Morris PG, Walshe JM , Crown J, O'Mahony D, Falcon A, Egan K, Hernando A,
Teiserskiene A, Kelly CM, Coate L and Hennessy BT
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr OT3-06-01.
http://cancerres.aacrjournals.org/content/79/4_Supplement/OT3-06-01
SI POSTER
GEICAM/2006-03 y GEICAM/2006-14
Genome copy number entropy as predictor of response for neoadjuvant therapy
in early breast cancer
Alba E, Rueda OM, Lluch A, Albanell J, Suet-Feung Chin, Chacón López-Muñiz JI,
Calvo L, De la Haba-Rodriguez J, Bermejo B, Ribelles N, Sánchez Rovira P, Plazaola
A, Barnadas A, Cirauqui B, Ramos Vázquez M, Arcusa A, Carrasco E, Herranz J,
Chiesa M, Caballero R, Santonja A, Rojo F, Caldas C
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr P5-12-03.
http://cancerres.aacrjournals.org/content/79/4_Supplement/P5-12-03
SI POSTER
GEICAM/2006-11 (LEA) (análisis conjunto con otros estudios)
A clinical calculator to predict disease outcomes in women with hormone
receptor-positive advanced stage breast cancer treated with first-line endocrine
therapy
Polley M-YC, Dickler MN, Johnston S, Goetz MP, de la Haba J, Loibl S, Mehta RS,
Bergh J, Roberston J, Barlow W, Liu H, Tenner K, Martin M
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr P2-07-05.
http://cancerres.aacrjournals.org/content/79/4_Supplement/P2-07-05
12
NO POSTER
GEICAM/2015-05 (POSITIVE)
POSITIVE: A study evaluating Pregnancy, disease outcome and safety of
interrupting endocrine therapy for premenopausal women with endocrine
responsIVE breast cancer who desire pregnancy (IBCSG 48-14/BIG 8-13)
Pagani O, Partridge AH, Peccatori F, Azim HA, Colleoni M, Saura C, Kroep JR, Warner
E, Gombos A, Sætersdal AB, Ruggeri M, Gelber RD, Sun Z
Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8;
San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract
nr OT1-01-06.
http://cancerres.aacrjournals.org/content/79/4_Supplement/OT1-01-06
LISTADO DE MANUSCRITOS PUBLICADOS
Artículos de revisión
1. New Horizons in Breast Cancer, the Promise of Immunotherapy.
de la Cruz-Merino L, Palazón Carrión N, Henao Carrasco F, Nogales Fernández E, Álamo de la
Gala MC, Vallejo Benítez A, Chiesa M, Sánchez-Margalet V; GEICAM (Spanish Breast Cancer
Research Group) and GÉTICA (Spanish Group for Cancer Immuno-Biotherapy).
Clin Transl Oncol. 2018 Jun 18. doi: 10.1007/s12094-018-1907-3. [Epub ahead of print].
Abstract:
Immunology and immunotherapy of cancer is an expanding field in oncology, with recent great
achievements obtained through the new successful approaches implemented to circumvent immune
evasion, which is undoubtedly considered a novel hallmark of cancer. Translational research in this topic
has revealed targets that can be modulated in the clinical setting with new compounds and strategies. Like
most of the tumors, breast cancer is considered a complex and heterogeneous disease in which host
immune responses have been also recently demonstrated of critical relevance. T infiltrating lymphocyte
measurement is suggested as a powerful new tool necessary to predict early breast cancer evolution,
especially for the her2-positive and triple-negative subtypes. Other biomarkers in tissue and peripheral
blood are under intense scrutiny to ascertain their eventual role as prognostic and/or predictive factors.
This background has fueled the interest in developing clinical research strategies to test activity of modern
immunotherapy in breast cancer, which constitutes the main focus of this review.
Artículos de estudios con promotor GEICAM
13
Estudios GEICAM/2006-03 y GEICAM/2006-14
2. Shallow whole genome sequencing for robust copy number profiling of formalin-
fixed paraffin-embedded breast cancers.
Chin SF, Santonja A, Grzelak M, Ahn S, Sammut SJ, Clifford H, Rueda OM, Pugh M,
Goldgraben MA, Bardwell HA, Cho EY, Provenzano E, Rojo F, Alba E, Caldas C.
Exp Mol Pathol. 2018 Jun;104(3):161-169. doi: 10.1016/j.yexmp.2018.03.006. Epub 2018
Mar 31.
Abstract:
Pathology archives with linked clinical data are an invaluable resource for translational research, with the
limitation that most cancer samples are formalin-fixed paraffin-embedded (FFPE) tissues. Therefore, FFPE
tissues are an important resource for genomic profiling studies but are under-utilised due to the low
amount and quality of extracted nucleic acids. We profiled the copy number landscape of 356 breast
cancer patients using DNA extracted FFPE tissues by shallow whole genome sequencing. We generated a
total of 491 sequencing libraries from 2 kits and obtained data from 98.4% of libraries with 86.4% being of
good quality. We generated libraries from as low as 3.8 ng of input DNA and found that the success was
independent of input DNA amount and quality, processing site and age of the fixed tissues. Since copy
number alterations (CNA) play a major role in breast cancer, it is imperative that we are able to use FFPE
archives and we have shown in this study that sWGS is a robust method to do such profiling.
Estudio GEICAM/9906
3. Outcomes of single versus double hormone receptor-positive breast cancer. A
GEICAM/9906 sub-study.
Ethier JL, Ocaña A, Rodríguez Lescure A, Ruíz A, Alba E, Calvo L, Ruíz-Borrego M, Santaballa
A, Rodríguez CA, Crespo C, Ramos M, Gracia Marco J, Lluch A, Álvarez I, Casas M, Sánchez-
Aragó M, Carrasco E, Caballero R, Amir E, Martin M.
Eur J Cancer. 2018 May;94:199-205. doi: 10.1016/j.ejca.2018.02.018. Epub 2018 Mar 21.
Abstract:
BACKGROUND: Retrospective data suggest better outcomes for patients with double hormonal receptor
(oestrogen [ER] and progesterone receptor [PgR])-positive (dHR+) early breast cancer, compared with
single hormonal receptor-positive, sHR+, (ER+/PgR- or ER-/PgR+) disease. Here, we evaluate the
classification according to intrinsic subtypes and clinical outcomes of sHR+ versus dHR+ in HER2-
negative breast cancer patients enrolled in GEICAM/9906 study (NCT00129922).
14
METHODS: Archival tumours were retrieved retrospectively for the analysis of ER, PgR and HER2 status
and classified into intrinsic subtypes using the PAM50 gene expression assay. Disease-free survival (DFS)
and overall survival (OS) were explored using a Cox proportional hazard analysis.
RESULTS: Data on intrinsic subtypes were available in 571 (50%) patients with ER+ and/or PR+, and
HER2-negative primary tumours. The incidence of luminal A and luminal B subtypes were 52%/36% in
dHR+ tumours (ER+/PgR+), and 15%/58% in ER+/PgR-tumours. ER-/PgR+ tumours were mainly luminal
A (52%). Compared with ER+/PgR+ patients, DFS was similar in ER-/PgR+ (hazard ratio [HR] 1.15, 95%
confidence interval [CI] 0.57-2.34, p = 0.70) but worse in ER+/PgR- patients (HR 1.60, 95% CI 1.12-2.28, p
< 0.01). Similar results were observed for OS (HR 1.50, p = 0.30 and HR 1.86, p < 0.01, respectively).
CONCLUSIONS: The ER+/PgR- group is characterised by higher proliferation and worse outcomes. In
spite of the ER-/PgR+ subgroup resembles ER+/PgR+ disease in terms of molecular subtypes and
outcomes, the small number of patients in this subgroup prevents from drawing any conclusions.
TRIAL REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005).
CLINICALTRIALS.
GOV IDENTIFIER: NCT00129922 (retrospectively registered 10/08/2005).
4. Prognostic role for the derived neutrophil to lymphocyte ratio in early breast
cancer: a GEICAM/9906 substudy.
Templeton AJ, Rodríguez-Lescure Á, Ruíz A, Alba E, Calvo L, Ruíz-Borrego M, Santaballa A,
Rodríguez CA, Crespo C, Ramos M, Gracia-Marco JM, Lluch A, Álvarez I, Casas MI, Sánchez-
Aragó M, Caballero R, Carrasco E, Amir E, Martin M, Ocaña A; GEICAM 9906 Study
Investigators.
Clin Transl Oncol. 2018 May 15. doi: 10.1007/s12094-018-1885-5. [Epub ahead of print].
Abstract:
PURPOSE: Elevated markers of host inflammation, a hallmark of cancer, have been associated with
worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-
lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer.
PATIENTS AND METHODS: This was a retrospective analysis of 1246 patients with lymph node-positive,
operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study
evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference
15
between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival
(DFS) and overall survival were explored using a Cox proportional hazard analysis.
RESULTS: The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10
years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%,
HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08-1.71]. In
the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However,
dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+
population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32,
p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched
tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the
treatment arm and dNLR.
CONCLUSION: Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative
early breast cancer.
TRIAL REGISTRATION: EudraCT: 2005-003108-12 (retrospectively registered 28/06/2005).
ClinicalTrials.gov Identifier: NCT00129922 (retrospectively registered 10/08/2005). Results of this study
were presented in part at the 2016 ESMO conference October 7-11, 2016, Copenhagen, Denmark (oral
presentation).
Estudio GEICAM/2006-03
5. Triple negative breast cancer subtypes and pathologic complete response rate to
neoadjuvant chemotherapy.
Santonja A, Sánchez-Muñoz A, Lluch A, Chica-Parrado MR, Albanell J, Chacón JI, Antolín S,
Jerez JM, de la Haba J, de Luque V, Fernández-De Sousa CE, Vicioso L, Plata Y, Ramírez-
Tortosa CL, Álvarez M, Llácer C, Zarcos-Pedrinaci I, Carrasco E, Caballero R, Martín M, Alba
E.
Oncotarget. 2018 May 29;9(41):26406-26416. doi: 10.18632/oncotarget.25413. eCollection
2018 May 29.
Abstract:
Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that
differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the
clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant
chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined
pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines and/or
taxanes +/- carboplatin. We explored the clinicopathological characteristics of Lehmann subtypes and their
association with the pathologic complete response (pCR) to different treatments. The global pCR rate was
37%, and it was unevenly distributed within Lehmann's subtypes. Basal-like 1 (BL1) tumors exhibited the
16
highest pCR to carboplatin containing regimens (80% vs 23%, p=0.027) and were the most proliferative
(Ki-67>50% of 88.2% vs. 63.7%, p=0.02). Luminal-androgen receptor (LAR) patients achieved the lowest
pCR to all treatments (14.3% vs 42.7%, p=0.045 when excluding mesenchymal stem-like (MSL) samples)
and were the group with the lowest proliferation (Ki-67≤50% of 71% vs 27%, p=0.002). In our cohort, only
tumors with LAR phenotype presented non-basal-like intrinsic subtypes (HER2-enriched and luminal A).
TNBC patients present tumors with a high genetic diversity ranging from highly proliferative tumors, likely
responsive to platinum-based therapies, to a subset of chemoresistant tumors with low proliferation and
luminal characteristics.
Estudio GEICAM/2012-12 (EDALINE)
6. A phase Ib study of sonidegib (LDE225), an oral small molecule inhibitor of
smoothened or Hedgehog pathway, in combination with docetaxel in triple
negative advanced breast cancer patients: GEICAM/2012-12 (EDALINE) study.
Ruiz-Borrego M, Jimenez B, Antolín S, García-Saenz JA, Corral J, Jerez Y, Trigo J,
Urruticoechea A, Colom H, Gonzalo N, Muñoz C, Benito S, Caballero R, Bezares S, Carrasco
E, Rojo F, Martín M.
Invest New Drugs. 2018 Jun 9. doi: 10.1007/s10637-018-0614-9. [Epub ahead of print].
Abstract:
Up-regulation of the Hedgehog (Hh) pathway is implicated in the genesis of a wide range of tumors
including triple negative breast cancer (TNBC). Sonidegib is a potent and selective oral inhibitor of Smo, a
key component of the Hh signaling pathway. We designed a phase I clinical study to explore the
combination of sonidegib plus docetaxel (fixed dose at 75 mg/m2) in advanced TNBC patients. The
primary objective was to ascertain the combination's maximum tolerated dose and the recommended
phase II dose (RP2D), based on dose limiting toxicities (DLTs) in the first 2 cycles. A standard "3 + 3"
design was followed including three dose levels (DL) of sonidegib: 400 mg (DL1), 600 mg (DL2), and 800
mg (DL3). Twelve patients were included. Sonidegib 800 mg orally q.d. plus docetaxel 75 mg/m2 given
intravenously on day 1 of 21-day cycles was established as the RP2D. No DLTs were observed at any DL.
The median number of administered cycles at DL3 was 8 (range: 6 to 9). Grade 3 adverse events (AEs) at
DL3 were neutropenia (66.7%), CPK increase (33.3%), leukopenia (33.3%), and paresthesia (33.3%),
grade 4 AEs were not reported at this DL. At the RP2D, the combination showed antitumor activity in three
out of 10 patients with measurable disease. Median time to progression for the overall study was 42.5 days
(95% Confidence Interval: 29-155), and 188 days at DL3. No drug-to-drug interactions between sonidegib
and docetaxel were found in the PK assessment. TRIAL REGISTRATION: EudraCT study number: 2013-
001750-96. Study GEICAM/2012-12. ClinicalTrials.gov: NCT02027376.
17
7. Targeting stromal remodeling and cancer stem cell plasticity to overcome
chemoresistance in triple negative breast cancer.
Cazet AS, Hui MN, Elsworth BL, Wu SZ, Roden D, Chan CL, Skhinas JN, Collot R, Yang J,
Harvey K, Johan MZ, Cooper C, Nair R, Herrmann D, McFarland A, Deng N, Ruiz-Borrego M,
Rojo F, Trigo JM, Bezares S, Caballero R, Lim E, Timpson P, O'Toole S, Watkins DN, Cox TR,
Samuel MS, Martín M, Swarbrick A.
Nat Commun. 2018 Jul 24;9(1):2897. doi: 10.1038/s41467-018-05220-6.
Abstract:
The cellular and molecular basis of stromal cell recruitment, activation and crosstalk in carcinomas is
poorly understood, limiting the development of targeted anti-stromal therapies. In mouse models of triple
negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-
associated fibroblasts (CAFs) to provide a supportive niche for the acquisition of a chemo-resistant, cancer
stem cell (CSC) phenotype via FGF5 expression and production of fibrillar collagen. Stromal treatment of
patient-derived xenografts with smoothened inhibitors (SMOi) downregulates CSC markers expression and
sensitizes tumors to docetaxel, leading to markedly improved survival and reduced metastatic burden. In
the phase I clinical trial EDALINE, 3 of 12 patients with metastatic TNBC derived clinical benefit from
combination therapy with the SMOi Sonidegib and docetaxel chemotherapy, with one patient experiencing
a complete response. These studies identify Hedgehog signaling to CAFs as a novel mediator of CSC
plasticity and an exciting new therapeutic target in TNBC.
18
Artículos de estudios con promotor no GEICAM
Estudio GEICAM/2012-10 (ETNA)
8. Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by
Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-
The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial: A
Randomized Phase 3 Clinical Trial.
Gianni L, Mansutti M, Anton A, Calvo L, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chacon
JI, Chan A, Morales S, Alvarez I, Plazaola A, Zambetti M, Redfern AD, Dittrich C, Dent RA,
Magazzù D, De Fato R, Valagussa P, Tusquets I.
JAMA Oncol. 2018 Mar 1;4(3):302-308. doi: 10.1001/jamaoncol.2017.4612.
Abstract:
IMPORTANCE: Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes
have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-
based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound
nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a
significantly higher rate of pCR in the GeparSepto trial.
OBJECTIVE: To determine whether nab-paclitaxel improves the outcomes of early and locally advanced
human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast cancer compared with
paclitaxel when delivered in a neoadjuvant setting.
DESIGN, SETTING AND PARTICIPANTS: In this multicenter, open-label study, in collaboration with
Grupo Español de Investigación en Cancer de Mama (GEICAM) and Breast Cancer Research Center-
Western Australia (BCRC-WA), patients with newly diagnosed and centrally confirmed ERBB2/HER2-
negative breast cancer were recruited. Participants were randomly allocated to paclitaxel, 90 mg/m2 (349
patients), or nab-paclitaxel, 125 mg/m2 (346 patients). The 2 drugs were given on weeks 1, 2, and 3
followed by 1 week of rest for 4 cycles before 4 cycles of an anthracycline regimen per investigator choice.
19
MAIN OUTCOMES AND MEASURES: The primary end point was the rate of pCR, defined as absence of
invasive cells in the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A secondary end
point was to assess tolerability and safety of the 2 regimens.
RESULTS: From May 2013 to March 2015, 814 patients were registered to the study; 695 patients met
central confirmation eligibility and were randomly allocated to receive either paclitaxel (349), or nab-
paclitaxel (346) (median age, 50 years; range, 25-79 years). The intention-to-treat analysis of the primary
end point pCR revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not statistically
significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77; 95% CI, 0.52-1.13; P = .19). Overall, 38
of 335 patients (11.3%) 11.3% of patients had at least 1 serious adverse event in the paclitaxel arm and 54
of 337 patients (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or higher occurred in 6
of 335 patients (1.8%) and in 15 of 337 (4.5%), respectively.
CONCLUSIONS AND RELEVANCE: The improved rate of pCR after nab-paclitaxel was not statistically
significant. The multivariate analysis revealed that tumor subtype (triple-negative vs luminal B-like) was the
most significant factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01822314.
Estudio GEICAM/2002-04 (CALOR)
9. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional
Recurrence of Breast Cancer: Final Analysis of the CALOR Trial.
Wapnir IL, Price KN, Anderson SJ, Robidoux A, Martín M, Nortier JWR, Paterson AHG, Rimawi
MF, Láng I, Baena-Cañada JM, Thürlimann B, Mamounas EP, Geyer CE Jr, Gelber S, Coates
AS, Gelber RD, Rastogi P, Regan MM, Wolmark N, Aebi S; International Breast Cancer Study
Group; NRG Oncology, GEICAM Spanish Breast Cancer Group, BOOG Dutch Breast Cancer
Trialists' Group; Breast International Group.
J Clin Oncol. 2018 Apr 10;36(11):1073-1079. doi: 10.1200/JCO.2017.76.5719. Epub 2018
Feb 14.
Abstract:
Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant
metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial
investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of
median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional
follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized
trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were
randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and
20
location of ILRR. Patients with hormone receptor-positive ILRR received adjuvant endocrine therapy.
Radiation therapy was mandated for patients with microscopically involved margins, and anti-human
epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS),
overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients
were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27
DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios
(HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively)
in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively)
in patients with ER-positive ILRR (Pinteraction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and 0.94 (95%
CI, 0.47 to 1.85), respectively, for breast cancer-free interval (Pinteraction = .034) and 0.48 (95% CI, 0.19 to
1.20) and 0.70 (95% CI, 0.32 to 1.55), respectively, for overall survival (Pinteraction = .53). Results for the
three end points were consistent in multivariable analyses adjusting for location of ILRR, prior CT, and
interval from primary surgery. Conclusion The final analysis of CALOR confirms that CT benefits patients
with resected ER-negative ILRR and does not support the use of CT for ER-positive ILRR.
Estudio GEICAM/2014-02 (BRIGHTNESS)
10. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to
standard neoadjuvant chemotherapy in triple-negative breast cancer
(BrighTNess): a randomised, phase 3 trial.
Loibl S, O'Shaughnessy J, Untch M, Sikov WM, Rugo HS, McKee MD, Huober J, Golshan M,
von Minckwitz G, Maag D, Sullivan D, Wolmark N, McIntyre K, Ponce Lorenzo JJ, Metzger Filho
O, Rastogi P, Symmans WF, Liu X, Geyer CE Jr.
Lancet Oncol. 2018 Apr;19(4):497-509. doi: 10.1016/S1470-2045(18)30111-6. Epub 2018
Feb 28.
Abstract:
BACKGROUND: Although several randomised trials in patients with triple-negative breast cancer have
shown that the addition of carboplatin, with or without poly(ADP-ribose) polymerase (PARP) inhibitors, to
neoadjuvant chemotherapy increases the likelihood of achieving a pathological complete response, the
use of these therapies in this setting has remained controversial. The BrighTNess trial was designed to
assess the addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard
neoadjuvant chemotherapy in triple-negative breast cancer.
METHODS: We did a phase 3, randomised, double-blind, placebo-controlled trial (BrighTNess) across 145
sites in 15 countries. Patients aged 18 years and older with previously untreated histologically or
cytologically confirmed clinical stage II-III triple-negative breast cancer, who were candidates for potentially
curative surgery and had an Eastern Cooperative Oncology Group performance status of 0 or 1, were
randomly assigned (2:1:1) by an interactive response technology system via permuted blocks (block size
of four) within strata to receive one of three segment 1 regimens: paclitaxel (80 mg/m2 intravenously
weekly for 12 doses) plus carboplatin (area under the curve 6 mg/mL per min, intravenously every 3
21
weeks, for four cycles) plus veliparib (50 mg orally, twice a day); paclitaxel plus carboplatin plus veliparib
placebo (twice a day); or paclitaxel plus carboplatin placebo (every 3 weeks for four cycles) plus veliparib
placebo. Following segment 1, all patients were assigned to segment 2 in which they received doxorubicin
and cyclophosphamide every 2-3 weeks for four cycles. Randomisation for segment 1 was stratified by
germline BRCA mutation status, nodal stage, and planned schedule of doxorubicin and cyclophosphamide
administration. The primary endpoint was pathological complete response in breast and lymph nodes as
determined by site pathologists following completion of neoadjuvant therapy. Efficacy analyses were done
by intention to treat and safety analyses included all patients who received at least one dose of study
treatment. These are the first results of an ongoing clinical trial; the data cutoff for the analyses presented
was Dec 8, 2016. This study is registered with ClinicalTrials.gov, number NCT02032277.
FINDINGS: Between April 4, 2014, and March 18, 2016, 634 patients were randomly assigned: 316 to
paclitaxel plus carboplatin plus veliparib, 160 to paclitaxel plus carboplatin, and 158 to paclitaxel alone.
The proportion of patients who achieved a pathological complete response was higher in the paclitaxel,
carboplatin, and veliparib group than in patients receiving paclitaxel alone (168 [53%] of 316 patients vs 49
[31%] of 158, p<0·0001), but not compared with patients receiving paclitaxel plus carboplatin (92 [58%] of
160 patients, p=0·36). Grade 3 or 4 toxicities, and serious adverse events were more common in patients
receiving carboplatin, whereas veliparib did not substantially increase toxicity. The most common grade 3
or 4 events overall were neutropenia (352 [56%] of 628 patients), anaemia (180 [29%]), and
thrombocytopenia (75 [12%]) through complete treatment, and febrile neutropenia (88 [15%] of 601
patients) during segment 2. The most common serious adverse events were febrile neutropenia (80 [13%]
of 628 patients) and anaemia (20 [3%]).
INTERPRETATION: Although the addition of veliparib and carboplatin to paclitaxel followed by doxorubicin
and cyclophosphamide improved the proportion of patients with triple-negative breast cancer who
achieved a pathological complete response, the addition of veliparib to carboplatin and paclitaxel did not.
Increased toxicities with the addition of carboplatin (with or without veliparib) to paclitaxel were
manageable and did not substantially affect treatment delivery of paclitaxel followed by doxorubicin and
cyclophosphamide. Given the consistent results with previous studies, the addition of carboplatin appears
to have a favourable risk to benefit profile and might be considered as a potential component of
neoadjuvant chemotherapy for patients with high-risk, triple-negative breast cancer.
FUNDING: AbbVie.
22
Estudio GEICAM/2013-07_TRIO-023 (EMBRACA)
11. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA
Mutation.
Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, Fehrenbacher L, Yerushalmi R,
Mina LA, Martin M, Roché H, Im YH, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann
W, Blum JL.
N Engl J Med. 2018 Aug 23;379(8):753-763. doi: 10.1056/NEJMoa1802905. Epub 2018 Aug
15.
Abstract:
BACKGROUND: The poly(adenosine diphosphate-ribose) inhibitor talazoparib has shown antitumor
activity in patients with advanced breast cancer and germline mutations in BRCA1 and BRCA2 (
BRCA1/2).
METHODS: We conducted a randomized, open-label, phase 3 trial in which patients with advanced breast
cancer and a germline BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once
daily) or standard single-agent therapy of the physician's choice (capecitabine, eribulin, gemcitabine, or
vinorelbine in continuous 21-day cycles). The primary end point was progression-free survival, which was
assessed by blinded independent central review.
RESULTS: Of the 431 patients who underwent randomization, 287 were assigned to receive talazoparib
and 144 were assigned to receive standard therapy. Median progression-free survival was significantly
longer in the talazoparib group than in the standard-therapy group (8.6 months vs. 5.6 months; hazard
ratio for disease progression or death, 0.54; 95% confidence interval [CI], 0.41 to 0.71; P<0.001). The
interim median hazard ratio for death was 0.76 (95% CI, 0.55 to 1.06; P=0.11 [57% of projected events]).
The objective response rate was higher in the talazoparib group than in the standard-therapy group
(62.6% vs. 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P<0.001). Hematologic grade 3-4 adverse events
(primarily anemia) occurred in 55% of the patients who received talazoparib and in 38% of the patients
who received standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38% of the
patients, respectively. Patient-reported outcomes favored talazoparib; significant overall improvements and
significant delays in the time to clinically meaningful deterioration according to both the global health
status-quality-of-life and breast symptoms scales were observed.
CONCLUSIONS: Among patients with advanced breast cancer and a germline BRCA1/2 mutation, single-
agent talazoparib provided a significant benefit over standard chemotherapy with respect to progression-
free survival. Patient-reported outcomes were superior with talazoparib (funded by Medivation [Pfizer];
EMBRACA ClinicalTrials.gov number, NCT01945775).
23
Departamento gestor de la publicación: no aplica.
12. Quality of life with talazoparib versus physician’s choice of chemotherapy in
patients with advanced breast cancer and germline BRCA1/2 mutation: patient-
reported outcomes from the EMBRACA phase III trial.
Ettl J, Quek RGW, Lee KH, Rugo HS, Hurvitz S, Gonçalves A, Fehrenbacher L, Yerushalmi R,
Mina LA, Martin M, Roché H, Im YH, Markova D, Bhattacharyya H, Hannah AL, Eiermann W,
Blum JL, Litton JK.
Ann Oncol. 2018 Sep 1;29(9):1939-1947. doi: 10.1093/annonc/mdy257.
Abstract:
BACKGROUND: In the EMBRACA phase III trial, talazoparib (1 mg daily, orally) demonstrated a
statistically significant improvement in PFS versus physician's choice of chemotherapy (PCT; capecitabine,
eribulin, gemcitabine, or vinorelbine) in patients with HER2-negative advanced breast cancer carrying a
germline BRCA1/2 mutation; we evaluated patient-reported outcomes (PROs).
PATIENTS AND METHODS: Patients were randomized 2:1 to receive talazoparib or PCT. PROs were
assessed at day 1 (baseline), the start of each treatment cycle (every 3 weeks), and at the end of
treatment, using the European Organisation for Research and Treatment of Cancer Quality of Life
Questionnaire Core 30 (EORTC QLQ-30) and its breast cancer module, QLQ-BR23. Prespecified
exploratory analyses included a longitudinal mixed-effect model comparing treatment arms and a time to
definitive clinically meaningful deterioration (TTD) analysis carried out in the global health status/quality of
life (GHS/QoL), and all functional and symptom scales from the EORTC QLQ-C30 and -BR23
questionnaires. Between-arm TTD comparisons were made using a stratified log-rank test and a Cox
proportional hazards model.
RESULTS: Baseline scores were similar between arms. Statistically significant estimated overall
improvement from baseline in GHS/QoL was seen for talazoparib compared with statistically significant
deterioration for PCT {3.0 [95% confidence interval (CI) 1.2, 4.8] versus -5.4 [95% CI -8.8, -2.0]; between
arms, P < 0.0001}. A statistically significant greater delay was observed in TTD in GHS/QoL, favoring
talazoparib over PCT [hazard ratio, 0.38 (95% CI 0.26, 0.55; median, 24.3 versus 6.3 months, respectively;
P < 0.0001)]. A statistically significant overall change and a statistically significant delay in TTD, all favoring
talazoparib, were also observed in multiple functions and symptoms.
24
CONCLUSION: Patients who received talazoparib had significant overall improvements and significant
delay in TTD in multiple cancer-related and breast cancer-specific symptoms, functions, and GHS/QoL.
ClinicalTrials.gov: NCT01945775.
GEICAM/2011-01 (PERTAIN)
13. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab,
in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-
Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A
Randomized, Open-Label Phase II Trial.
Rimawi M, Ferrero JM, de la Haba-Rodriguez J, Poole C, De Placido S, Osborne CK, Hegg R,
Easton V, Wohlfarth C, Arpino G; PERTAIN Study Group.
J Clin Oncol. 2018 Oct 1;36(28):2826-2835. doi: 10.1200/JCO.2017.76.7863. Epub 2018 Aug
14.
Abstract:
PURPOSE: To assess pertuzumab plus trastuzumab and an aromatase inhibitor (AI) in patients with
human epidermal growth factor receptor 2 (HER2)-positive and hormone receptor-positive
metastatic/locally advanced breast cancer (MBC/LABC).
PATIENTS AND METHODS: The PERTAIN trial (NCT01491737) is an ongoing randomized, open-label,
multicenter-80 sites and eight countries-phase II trial. Patients have HER2-positive, hormone receptor-
positive MBC/LABC and no prior systemic therapy with the exception of endocrine. Random assignment
was 1:1 to intravenous pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) plus
trastuzumab (8 mg/kg followed by 6 mg/kg every 3 weeks), and oral anastrozole (1 mg every day) or
letrozole (2.5 mg every day), or trastuzumab and an AI. Induction intravenous docetaxel every 3 weeks or
paclitaxel every week could be administered for 18 to 24 weeks at the investigator's discretion (decided
before but given after random assignment). Primary end point was progression-free survival (PFS).
Patients were stratified by whether they received induction chemotherapy and their time since adjuvant
hormone therapy.
RESULTS: One hundred twenty-nine patients were randomly assigned per arm (February 2012 to October
2014; intent-to-treat populations); 75 in one arm and 71 in the other were chosen to receive induction
chemotherapy. Stratified median PFS was 18.89 months (95% CI, 14.09 to 27.66 months) in the
25
pertuzumab plus trastuzumab arm and 15.80 months (95% CI, 11.04 to 18.56 months) in the trastuzumab
arm (stratified hazard ratio, 0.65; 95% CI, 0.48 to 0.89; P = .0070). Serious adverse events (AEs) were
reported for 42 (33.1%) of 127 and 24 (19.4%) of 124 patients in the safety populations of the pertuzumab
plus trastuzumab and trastuzumab arms, respectively. Rates of grade ≥ 3 AEs were 64 (50.4%) of 127 and
48 (38.7%) of 124, respectively. There were no deaths as a result of AEs.
CONCLUSION: PERTAIN met its primary PFS end point. Pertuzumab plus trastuzumab and an AI is
effective for the treatment of HER2-positive MBC/LABC. The safety profile was consistent with previous
trials of pertuzumab plus trastuzumab.
Estudio GEICAM/2014-04_TRIO024 (ABRAZO)
14. A Phase II Study of Talazoparib After Platinum or Cytotoxic Nonplatinum
Regimens in Patients With Advanced Breast Cancer and Germline BRCA1/2
Mutations (ABRAZO).
Turner NC, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmaña J, Fasching
PA, Hurvitz SA, Wardley AM, Chappey C, Hannah AL, Robson ME, on behalf of the ABRAZO
Srudy.
Clin Cancer Res. 2018 Dec 18. pii: clincanres.1891.2018. doi: 10.1158/1078-0432.CCR-18-
1891. [Epub ahead of print].
Abstract:
PURPOSE: To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast
cancer (aBC).
EXPERIMENTAL DESIGN: ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of
talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no
progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic
regimens (cohort 2) for aBC. Primary endpoint was confirmed objective response rate (ORR) by
independent radiological assessment.
RESULTS: We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016.
Median age was 50 (range, 31-75) years. Triple-negative breast cancer incidence was 59% (cohort 1) and
17% (cohort 2). Median number of prior cytotoxic regimens for aBC was two and four, respectively.
Confirmed ORR was 21% (95% CI, 10 to 35) (cohort 1) and 37% (95% CI, 22 to 55) (cohort 2). Median
duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33%
(BRCA2), 26% (TNBC) and 29% (hormone receptor positive). The most common allgrade adverse events
(AEs) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug
discontinuation in three (4%) patients. In an exploratory analysis, longer platinum-free interval was
associated with higher response rate in cohort 1 (0% ORR with interval <8 weeks; 47% ORR with interval
>6 months).
26
CONCLUSIONS: Talazoparib exhibited promising antitumor activity in patients with aBC and germline
BRCA mutation.