anexo: publicaciones 2018 comunicaciones a …...1 anexo: publicaciones 2018 comunicaciones a...

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


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



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)


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



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)



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



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



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



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



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



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



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



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


SI

ORAL

SESIÓN

PLENARIA


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


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


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


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



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



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







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



NO POSTER


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



NO POSTER


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



NO ORAL


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



CONGRESO DE LA SOCIEDAD ESPAÑOLA DE EPIDEMIOLOGÍA – 1

comunicación:

Un póster [EpiGEICAM-01].





8

PROMOTOR


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


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


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

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





https://www.google.es/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwi_2-O5n_ffAhUP3xoKHbkkAysQjRx6BAgBEAU&url=https://www.esmo.org/Conferences/ESMO-Immuno-Oncology-Congress-2018&psig=AOvVaw2c3PUfOsKM5vTni0iLvjfQ&ust=1547897971950754

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


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



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

http://cancerres.aacrjournals.org/content/79/4_Supplement/GS2-04

http://cancerres.aacrjournals.org/content/79/4_Supplement/PD9-04

11



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



nr 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



nr OT3-06-01.

http://cancerres.aacrjournals.org/content/79/4_Supplement/OT3-06-01

SI POSTER


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



nr 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



nr 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



nr 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


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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).

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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

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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

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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.

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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.

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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.

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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.

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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).

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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).

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CONCLUSIONS: Talazoparib exhibited promising antitumor activity in patients with aBC and germline

BRCA mutation.

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