Novedades en tratamiento con quimioterapia en Cáncer de Mama. Dr E Ciruelos S Oncología Médica Hospital 12 de Octubre, Madrid

Novedades en tratamiento con quimioterapia en Cáncer de Mama Dr E Ciruelos S Oncología Médica Hospital 12 de Octubre, Madrid

Evolución de la quimioterapia en cáncer de mama avanzado Mid 20 th century Late 20 th century Late 20 th century Early 21 st century Early chemotherapy CMF (VP) Anthracyclines Vinorelbine Taxanes Capecitabine Biological era begins Novel antitubulins Advanced cytotoxics CMF = cyclophosphamide + methotrexate + 5-flourouracil; VP = vincristine + prednisone

A quién tratar con QT?

Factores que determinan la elección del tratamiento en el cáncer de mama avanzado Características de la enfermedad Carga de enfermedad Respuesta a terapias previas Agresividad de la enfermedad Estatus de RH (ER y PgR) y HER2 Intervalo libre de enfermedad Terapia adyuvante previa Elección del tratamiento Disponibilidad Coste del tratamiento Guías y recomendaciones Características de la paciente Preferencia de la paciente (oral vs IV), toxicidades Aspectos socioeconómicos y psicológicos (ej.: distancia desde la casa y el hospital, costes) Edad, PS, comorbilidades Estado menopáusico: SI vs. NO ABC2 Guidelines, Ann Oncol 2014

ALGORITMO DE TRATAMIENTO Paciente postmenopáusica* con cancer de mama avanzado RH+ y HER2- Continuar con la terapia hormonal hasta progresión o toxicidad inaceptable Progresión Sin beneficio clínico luego de varios regímenes consecutivos de terapia hormonal O Enfermedad visceral sintomática Sí No Quimioterapia EECC con una nueva terapia hormonal

Cáncer de mama TN: Subtipos intrínsecos Prat A. The Oncologist 2013

Nuevas formulaciones: Nuevos fármacos

Nuevas formulaciones: Nuevos fármacos Nab-Paclitaxel

QT clásica: Nuevas formulaciones

Cáncer de mama metastásico: Nanotecnología Abraxane PFS, months 300 mg/m 2 q3w N Arm A (n = 76) Media n nab-paclitaxel 100 mg/m 2 N qw 3/4 Arm B (n = 76) Media n 150 mg/m 2 qw 3/4 Arm C (n = 74) Docetaxel 100 mg/m 2 q3w Arm D (n = 74) N Median N Median Overall P value a All patients 76 10.9 76 7.5 74 14.6 74 7.8.008 < 65 years 65 years 67 9 10.9 13.8 62 14 7.5 9.2 64 10 14.1 18.9 55 19 7.6 8.5.012.564 DM Visceral Nonvisceral Lesion sites < 5 5 Premenopausal Postmenopausal a Based on log-rank test. 64 12 39 25 26 49 10.9 16.4 10.2 12.1 11.0 10.9 61 15 37 24 14 62 7.5 7.7 8.7 6.9 7.5 7.5 DM, dominant metastasis; PFS, progression-free survival; q3w, every 3 weeks; qw 3/4, first 3 of 4 weeks. 59 15 38 21 21 53 13.1 > 19.2 13.1 14.1 12.9 14.6 67 7 41 26 12 60 7.8 11.0 7.6 7.8 5.6 8.4.022.575.417.009.137.022 Gradishar W. et al. ECCO. 2011 [Abstract 5060].

GeparSepto: Phase III Neoadjuvant Trial of nab-p vs sb-p Regimens in Early Breast Cancer Final Study Design (after 400 patients) 12 HER, human epidermal growth factor receptor; HR, hormone receptor; nab-p, nab-paclitaxel; sb-p, solvent-based paclitaxel. Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer GBG 69 GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium December 9-13, 2014; San Antonio, Texas. [oral S2-07].

GeparSepto: Phase III Neoadjuvant Trial of nab-p vs sb-p Regimens in Early Breast Cancer Primary Endpoint (pcr: ypt0 ypn0) 13 nab-p, nab-paclitaxel; pcr, pathological complete response; sb-p, solvent-based paclitaxel. Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer GBG 69 GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium December 9-13, 2014; San Antonio, Texas. [oral S2-07].

GeparSepto: Phase III Neoadjuvant Trial of nab-p vs sb-p Regimens in Early Breast Cancer Secondary Endpoints: pcr Rates According to Other Definitions 14 nab-p, nab-paclitaxel; pcr, pathological complete response; sb-p, solvent-based paclitaxel. Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer GBG 69 GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium December 9-13, 2014; San Antonio, Texas. [oral S2-07].

GeparSepto: Phase III Neoadjuvant Trial of nab-p vs sb-p Regimens in Early Breast Cancer pcr in Stratified Subgroups 15 Parameter Subgroup pcr, % P Value SPARC SPARC SPARC+ Ki67 Ki67 20% Ki67 >20% 28.8 vs 37.7 29.8 vs 48.3 19.6 vs 26.1 33.1 vs 44.0 0.003 0.074 0.137 0.001 Biological subtype HER2, HR+ HER2, HR HER2+, HR+ HER2+, HR 12.0 vs 16.0 25.7 vs 48.2 50.0 vs 56.4 66.7 vs 74.6 0.183 < 0.001 0.275 0.371 HER2 HER2 HER2+ 17.7 vs 27.0 54.1 vs 61.8 < 0.001 0.120 HR status HR HR+ 36.1 vs 56.1 25.6 vs 29.9 < 0.001 0.169 HER, human epidermal growth factor receptor; HR, hormone receptor; nab-p, nab-paclitaxel; pcr, pathological complete response; sb-p, solvent-based paclitaxel; SPARC, secreted protein acidic and rich in cysteine. Untch M, Jackisch C, Schneeweiss A, et al. A randomized phase III trial comparing nanoparticle-based paclitaxel with solvent-based paclitaxel as part of neoadjuvant chemotherapy for patients with early breast cancer GBG 69 GeparSepto. Oral presented at: San Antonio Breast Cancer Symposium December 9-13, 2014; San Antonio, Texas. [oral S2-07].

Nuevas formulaciones: Nuevos fármacos Etirinotecan

Etirinotecan (NKTR 102) Pegilado en polímero (prodroga inactiva) Se libera en capilares de microvasculatura tumoral Hidrólisis a droga activa Inhibición de síntesis de DNA No pico plasmático

Etirinotecan: Fase II en CMM NKTR-102 145 mg/m 2 q14 days ORR, RECIST v 1.0 n/n (%) Evaluable Patients NKTR-102 145 mg/m 2 q21 days TOTAL Prior A/T 7/22 (32%) 5/21 (24%) 12/43 (28%) Triple Negative 2/8 (25%) 5/10 (50%) 7/18 (39%) Prior A/T/C 2/6 (33%) 3/10 (30%) 5/16 (31%) Median PFS (m) 3.5 5.3 4.6 Median OS (m) 8.8 13.1 10.3 Awada A, et al. IMPAKT 2012

Etirinotecan: Estudio BEACON N=840 CMM o localmente recurrente 2-5 líneas previas QT 2 líneas en CMM Previo A, T y Cape R 1:1 NKTR-102 145 mg/m 2 /21d Tratamiento a elección (TPC) * Monoterapia (eribulina, ixabepilona, vinorelbina, gemcitabina, taxanos) PI: J. Cortés Estratificación Area geográfica Eribulina previa Subtipo histológico * Eribulina 40%, VNR 23%, gemcitabina 18%, taxano 15%, ixabepilona 4%

Etirinotecan: Estudio BEACON Median OS 12.4 vs 10.3 months (HR 0.87; p 0.08) Brain mets (67 pts): mos 10 vs 4.8 m (HR 0.51; p<0.01) Liver mets (456 pts): mos 10.9 vs 8.3 m (HR 0.73; p 0.002) Grade > 3 AEs: 48 vs 63% Perez EA, ASCO June 2015

Antimicrotúbulos no taxanos Eribulina

Eribulin s novel mechanism of inhibiting microtubule dynamics (Jordan et al., 2005) Eribulin 1 Eribulin inhibits microtubule growth Microtubule Dynamics Growing microtubule Microtubule Polymerization 3 Eribulin causes globular tubulin aggregates Eribulin MTOC Shortening microtubule 2 Microtubule Depolymerization Eribulin has no effect on microtubule shortening Globular tubulin aggregates MT drawing created by M. Asada, TRL, Eisai; later adapted by B. Littlefield, ERI

Phase II studies confirmed activity of eribulin in patients with pre-treated MBC 201 Study 1 (N=103): Prior taxane & anthracycline* 211 Study 2 (N=299): Prior taxane, anthracycline, & capecitabine* Primary endpoint: ORR with independent review Secondary endpoints: DOR, PFS, OS, AEs ORR: 11.5% Median DOR: 5.6 months Median PFS: 2.6 months 6-month PFS 25.9% (95% CI, 15.5, 36.3) Median OS: 9.0 months (range 0.5 27.2 months) 6-month survival 67.8% (95% CI, 58.0, 77.6) 1-year survival 45.7% (95% CI, 35.2, 56.2) ORR: 9.3% Median DOR: 4.1 months Median PFS: 2.6 months 6-month PFS 15.6% (95% CI, 10.7, 20.5) Median OS: 10.4 months 6-month survival 72.3% (95% CI, 66.9, 77.6) *MBC patients with progression of disease 6 months of last chemotherapy and, if present, pre-existing neuropathy grade 2 AEs = adverse events; CI = confidence interval; DOR = duration of response; MBC = metastatic breast cancer; ORR = overall response rate; OS = overall survival; PFS = progression-free survival 1. Vahdat L, Pruitt B et al. J Clin Oncol. 2009;27:2954 2961; 2. Cortes J, Vahdat L et al. J Clin Oncol. 2010;28:3922 3928

Halaven has been evaluated in two of the largest, Phase 3 randomised trials conducted in MBC 1,2 EMBRACE study 1 (N=762) Study 301 2 (N=1102) La indicación en segunda línea en la que se administró el fármaco a los s pacientes en el estudio 301 no está financiada por el sistema nacional de salud. 2 prior regimens for advanced disease Median of four prior chemotherapy regimens HER2-negative 74%; TNBC 19% Comparator: single TPC Primary endpoint: OS Secondary endpoints: PFS, ORR, DOR 2 prior regimens for advanced disease 3 prior chemotherapy regimens 1 prior chemotherapy: 573 patients All prior anthracycline/taxane (25/46% refractory) HER2-negative 68.5%; TNBC 26.0% Comparator: capecitabine Co-primary endpoints: OS and PFS Secondary endpoints: ORR, survival at 1, 2 and 3 years, QoL DOR, duration of response; ORR, objective response rate; QoL, quality of life; TPC, treatment of physician s choice. In EMBRACE study, TPC was defined as any single-agent chemotherapy, hormonal therapy or targeted therapy approved for the treatment of cancer, radiotherapy, or best supportive care. TPC was selected prior to randomisation to eliminate any bias. 1 1. Cortes J, et al. Lancet. 2011;377:914 923; 2. Kaufman PA, et al. J Clin Oncol. 20 Feb 2015.

Halaven has been evaluated in two of the largest, Phase 3 randomised trials conducted in MBC 1,2 EMBRACE study 1 (N=762) Study 301 2 (N=1102) La indicación en segunda línea en la que se administró el fármaco a los s pacientes en el estudio 301 no está financiada por el sistema nacional de salud. 2 prior regimens for advanced disease Median of four prior chemotherapy regimens HER2-negative 74%; TNBC 19% Comparator: single TPC Primary endpoint: OS Secondary endpoints: PFS, ORR, DOR 2 prior regimens for advanced disease 3 prior chemotherapy regimens 1 prior chemotherapy: 573 patients All prior anthracycline/taxane (25/46% refractory) HER2-negative 68.5%; TNBC 26.0% Comparator: capecitabine Co-primary endpoints: OS and PFS Secondary endpoints: ORR, survival at 1, 2 and 3 years, QoL DOR, duration of response; ORR, objective response rate; QoL, quality of life; TPC, treatment of physician s choice. In EMBRACE study, TPC was defined as any single-agent chemotherapy, hormonal therapy or targeted therapy approved for the treatment of cancer, radiotherapy, or best supportive care. TPC was selected prior to randomisation to eliminate any bias. 1 1. Cortes J, et al. Lancet. 2011;377:914 923; 2. Kaufman PA, et al. J Clin Oncol. 2015 [Epub ahead of print].

EMBRACE: Updated OS analysis Median OS, months Eribulin (n=508) 13.2 TPC (n=254) 10.5 HR 0.81 95% CI 0.67, 0.96 P value* 0.014 Analysis occurred at 589 events (deaths), representing 77% of the ITT population *Nominal P value from stratified log-rank test CI = confidence interval; HR = hazard ratio; ITT = intent-to-treat; OS = overall survival; TPC = treatment of physician s choice Cortes J, O Shaughnessy J et al. Lancet. 2011;377:914 923; Twelves C, Loesch D et al. San Antonio Breast Cancer Symposium. 2010;Poster P6-14-18

Halaven has been evaluated in two of the largest, Phase 3 randomised trials conducted in MBC 1,2 EMBRACE study 1 (N=762) Study 301 2 (N=1102) La indicación en segunda línea en la que se administró el fármaco a los s pacientes en el estudio 301 no está financiada por el sistema nacional de salud. 2 prior regimens for advanced disease Median of four prior chemotherapy regimens HER2-negative 74%; TNBC 19% Comparator: single TPC Primary endpoint: OS Secondary endpoints: PFS, ORR, DOR 2 prior regimens for advanced disease 3 prior chemotherapy regimens 1 prior chemotherapy: 573 patients All prior anthracycline/taxane (25/46% refractory) HER2-negative 68.5%; TNBC 26.0% Comparator: capecitabine Co-primary endpoints: OS and PFS Secondary endpoints: ORR, survival at 1, 2 and 3 years, QoL DOR, duration of response; ORR, objective response rate; QoL, quality of life; TPC, treatment of physician s choice. In EMBRACE study, TPC was defined as any single-agent chemotherapy, hormonal therapy or targeted therapy approved for the treatment of cancer, radiotherapy, or best supportive care. TPC was selected prior to randomisation to eliminate any bias. 1 1. Cortes J, et al. Lancet. 2011;377:914 923; 2. Kaufman PA, et al. J Clin Oncol. 20 Feb 2015.

Proportion of survival Study 301: A trend toward improved overall survival with eribulin vs capecitabine (ITT population) Study 301 Median OS (co-primary endpoint) vs capecitabine showed a numerical difference in favour of Halaven, but was not statistically significant 1.0 0.9 0.8 0.7 0.6 0.5 Median OS (months) Eribulin (n=554) 15.9 Capecitabine (n=548) 14.5 HR 0.879 95% CI 0.770, 1.003 P value* 0.0560 0.4 0.3 There was no difference in PFS between the 2 treatment arms 0.2 0.1 0.0 Number of subjects at risk 554 548 0 530 513 505 466 4 464 426 423 391 8 378 352 349 308 12 320 277 268 242 16 243 214 214 191 193 175 173 155 151 135 133 122 119 108 99 81 77 62 52 42 20 24 28 32 36 40 44 48 52 Time (months) *Stratified log-rank test based on geographical region and HER2 status. One-, 2-, and 3-year survival rates were 64.4% and 58.0% (P=0.04), 32.8% and 29.8% (P=0.32), and 17.8% and 14.5% (P=0.18) for eribulin and capecitabine, respectively. Halaven Summary of Product Characteristics. www.ema.europa.eu; Kaufman PA, et al. J Clin Oncol. 2015 [Epub ahead of print]. 38 33 32 27 26 23 22 17 15 13 13 12 9 10 7 2

Breast Cancer Res Treat. Sep 2014 DOI 10.1007/s10549-014-3144-y CLINICAL TRIAL Efficacy of eribulin in women with metastatic breast cancer: a pooled analysis of two phase 3 studies Chris Twelves Javier Cortes Linda Vahdat Martin Olivo Yi He Peter A. Kaufman Ahmad Awada

Proportion of survival Overall survival in the ITT population: 1.0 0.9 0.8 0.7 0.6 0.5 Median OS (months) Eribulin (n=1062) 15.2 Control (n=802) 12.8 HR 0.853 95% CI 0.768, 0.948 P value 0.0031 2.4 months difference 0.4 0.3 0.2 0.1 0.0 Number of subjects at risk 1062 802 1021 750 957 672 870 604 785 545 690 486 623 414 554 370 462 324 385 275 327 242 276 216 227 181 189 151 158 134 130 113 105 83 79 62 52 42 38 33 32 27 26 23 22 17 15 13 13 12 9 10 7 2 2 2 2 1 0 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 Time (months) Data on file ERI-104 Hazard ratio stratified by region, HER2 status, prior capecitabine use and study Overall survival curves adjusted by study 305 study data is updated 77% event analysis

Event/N Overall survival in HER2 subgroups Median OS (months) Subgroup Eribulin Control HR (95% CI) P value Eribulin Control Overall 832/1062 662/802 0.853 (0.768, 0.948) 0.0031 15.2 12.8 HER2 status Positive 139/169 110/123 0.815 (0.624, 1.063) 0.1345 13.5 12.2 Negative 581/748 467/572 0.841 (0.743, 0.952) 0.0062 15.2 12.3 Negative* 581/748 467/572 0.819 (0.722, 0.929) 0.0019 15.2 12.3 TNBC patients Yes 201/243 162/185 0.741 (0.599, 0.917) 0.0056 12.9 8.2 No 543/707 441/543 0.862 (0.757, 0.981) 0.0243 15.7 13.7 0.4 0.6 Favours eribulin 0.8 1.0 1.2 1.4 1.6 1.8 Favours control * Additionally stratified by triple-negative status

Toxicidad Estudio 301 Estudio 305 Toxicidad G3/4 Eribulina Capecitabina Eribulina Control HEMATOLOGICA Anemia 2% 1% 2-3% 4% Neutropenia 46% 5% 45% 21% Neutropenia febril 2% 1% 4% 1% Trombopenia 0.5% 1% NO HEMATOLOGICA Astenia/Fatiga 6% 6% 9% 10% Neuropatía sensitiva 3.5% 0.5% 9% 2% Alopecia 35% 4% 45% 10% Naúseas 0.2% 1.6% 1% 2% Sd Mano-pie 0% 14.5% Diarrea 1.1% 5.3%

Eribulin: New approved clinical indication in EU (*) HALAVEN monotherapy is indicated for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least two one chemotherapeutic regimen for advanced disease (see section 5.1). Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless patients were not suitable for these treatments (*) SmPC approved by EMA in June 2014.

Platinos: Nuevos datos clínicos

Antiangiogénicos: Nuevos datos clínicos

Bevacizumab en 1ª línea CMM

Bevacizumab en 1ª línea CMM

Bevacizumab en 1ª línea CMM

IMELDA: Open-label randomised phase III trial 3 6 cycles Previously untreated HER2-negative LR/mBC BEV 15 mg/kg + DOC 75 100 mg/m 2 d1 q3w CR, PR or SD Stratification factors ER status (positive vs negative) Visceral metastasis (present vs absent) Stable disease/response/non-measurable disease LDH concentration ( 1.5 vs >1.5 ULN) R 1:1 BEV 15 mg/kg d1 q3w BEV 15 mg/kg d1 + CAP 1000 mg/m 2 bid d1 14 q3w Treat to PD, unacceptable toxicity or withdrawal of consent CAP = capecitabine; CR = complete response; ER = oestrogen receptor; LDH = lactate dehydrogenase; PR = partial response; SD = stable disease; R = randomisation; ULN = upper limit of normal.

Withdrawn before treatment (N=3) Patient disposition Enrolled (N=287) Discontinued initial treatment (N=99) PD (N=41) AE/toxicity (N=31) Other reason (N=27) a a Withdrew consent/patient s decision (N=13), inclusion/exclusion criteria or protocol violation (N=5), investigator/medical decision (N=4), health authority/study termination (N=3), death (N=2) Treated in initial phase (N=284) Completed initial treatment and randomised (N=185) R AE = adverse event BEV alone (N=94) Treated (N=92) Untreated (N=2) BEV CAP (N=91) Treated (N=91)

Estimated probability Primary endpoint: PFS from time of randomisation 1.0 0.8 0.6 0.4 BEV (N=94) BEV CAP (N=91) Events, n (%) 83 (88) 69 (76) Median PFS, months (95% CI) Stratified hazard ratio (95% CI) Stratified 2-sided log-rank test 4.3 (3.9 6.8) 0.38 (0.27 0.55) p<0.0001 11.9 (9.8 15.4) 0.2 0 4.3 11.9 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 Time from randomisation (months) No. at risk BEV CAP 91 80 62 50 40 34 26 22 16 12 8 2 2 1 0 BEV 94 60 40 20 17 11 9 6 2

PFS in prespecified subgroups Subgroup No. of events/patients (%) Median PFS, months Unstratified hazard ratio (95% CI) BEV CAP BEV BEV CAP BEV Favours BEV CAP Favours BEV All (stratified) 69/91 (76) 83/94 (88) 11.9 4.3 Age <65 years 57/77 (74) 73/81 (90) 12.2 4.9 Age 65 years 12/14 (86) 10/13 (77) 11.7 4.3 Triple negative 19/25 (76) 21/21 (100) 7.6 3.3 Hormone receptor positive 50/66 (76) 62/73 (85) 13.0 6.1 ER positive a 48/64 (75) 59/69 (86) 14.1 4.9 ER negative a 21/27 (78) 24/25 (96) 7.6 3.8 <3 metastatic organ sites 39/48 (81) 33/40 (83) 10.4 6.2 3 metastatic organ sites 30/43 (70) 50/54 (93) 15.4 4.0 Visceral metastases a 47/62 (76) 60/65 (92) 11.9 4.2 No visceral metastases a 22/29 (76) 23/29 (79) 14.1 7.6 Response a 53/68 (78) 59/68 (87) 11.9 4.2 Stable disease a 13/20 (65) 21/22 (95) 19.3 4.9 LDH 1.5 ULN a 64/85 (75) 78/89 (88) 12.4 4.3 LDH >1.5 ULN a 5/6 (83) 5/5 (100) 3.0 4.1 a Stratification factors (data at randomisation)

Estimated probability IMELDA: 1.0 0.8 OS from time of randomisation BEV (N=94) BEV CAP (N=91) Events, n (%) 53 (56) 33 (36) 1-year OS rate (%) 72 90 2-year OS rate (%) 49 69 Stratified hazard ratio (95% CI) Stratified 2-sided log-rank 0.43 (0.26 0.69) p<0.0003 Median, months (95% CI) 23.7 39.0 (18.5 31.7) (32.3 NR) 0.6 0.4 0.2 0 23.7 (95% CI: 18.5 31.7) 39.0 (95% CI 32.3 NR) 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 Time from randomisation (months) No. at risk BEV CAP 91 87 84 78 72 70 64 60 54 47 36 21 10 4 0 0

Bevacizumab: biomarcadores predictivos

Miles D, ASCO 2013

Conclusiones Nuevas formulaciones: nab-placitaxel - significativamente mejor que paclitaxel en neoadyuvancia

Conclusiones Nuevas formulaciones: nab-placitaxel - significativamente mejor que paclitaxel en neoadyuvancia Nuevas formulaciones: Etirinotecan - significativamente mejor que irinotecan en algunos subgrupos

Conclusiones Nuevas formulaciones: nab-placitaxel - significativamente mejor que paclitaxel en neoadyuvancia Nuevas formulaciones: Etirinotecan - significativamente mejor que irinotecan en algunos subgrupos Nuevos antimicrotúbulos: Eribulina - tras antraciclinas y taxanos como alternativa a capecitabina

Conclusiones Platinos - en fenotipo triple negativo, fundamentalmente en basal like y BRCA mutado (línea germinal)

Conclusiones Platinos - en fenotipo triple negativo, fundamentalmente en basal like y BRCA mutado (línea germinal) Bevacizumab - en esquema de mantenimiento con capecitabina en pacientes respondedores a 1ª línea con taxano