CONTINUM ASISTENCIAL:

FACTORES DE DECISIÓN

Ana Mª López Muñoz

Hospital Universitario de Burgos

Richard M. Goldberg et al. The Oncologist2007;12:38–50

“Treatment is sequenced through phases, rather than lines, of therapy and

takes into account the long-term treatment plan for each patient”

“The central goal is to optimize survival, time without toxicity from

chemotherapy, and quality of life”

Additional

opportunities

The use of novel therapies and more

complex treatment strategies have

contributed to progressively increase

the median life expectancy

Additional

complexities

PACIENTE

Edad

PS

Comorbilidad

Preferencias

Socio-económicos

TUMOR TRATAMIENTO

Aspectos moleculares

Localización

Volumen tumoral

Temporalidad

Perfil eficacia

Toxicidad

Disponibilidad

Assessment of clinical condition of the patient

E. Van Cutsem et al. Annals of Oncology 2016; 27: 1386-1422

PACIENTE

- Age

- Performance status

- Organ function/Comorbilities

- Preference

- Socioeconomic

(a) Patients assessed as fit or unfit according to medical condition not due to malignant disease

D. Cunninghan et al. Lancet Oncology 2013

PHASE II TASCO1

E. V. Cutsem. WCGI 2018

PHASE III AVEX

8

OBJETIVO

TRATAMIENTO

1. EFICACIA

Biomarkers of chemotherapy sensitivity and toxicity:

• DPD testing before 5-FU administration remains an option but is not routinely recommended [II, D].

• UGT1A1 phenotyping remains an option and should be carried out in patients with a suspicion of UGT1A1 deficiency as reflected by

low conjugated bilirubin and in patients where an irinotecan dose of >180 mg/m2 per administration is planned [III, C].

• ERCC1 expression cannot be recommended for use as a biomarker for treatment decisions involving the use of oxaliplatin in routine

clinical practice, but could be included prospectively in clinical trials [III, D]

Fármacos aprobados para el tratamiento del CCRm:

Fluoropirimidinas, Oxaliplatino, Irinotecan, Panitumumab, Cetuximab, Bevacizumab,

Aflibercept, Ramucirumab, Regorafenib y TAS 102. (MSI (FDA): Pembrolizumab y

Nivolumab)

2. TOXICIDADBIOMARCADORES

TUMOR

All patients with metastatic colorectal cancer should have tumor tissue genotyped for RAS (KRAS and NRAS) and BRAF mutations.

Universal MMR* or MSI* testing is recommended in all patients with a personal history of colon or rectal cancer

NCCN Guidelines Version 2.2018 Colon Cancer

SIDENESS

¿ALGUNA NUEVA CONSIDERACIÓN CUANDO EL

OBJETIVO ES LA CITORREDUCCIÓN?

C. Cremollini et al. Annals of Oncology 2018

Patients with right-sided tumors achieved more relative benefit from the intensification of the chemotherapy

backbone in terms of both PFS and OS, and this advantage was independent of their RAS and BRAF status.

FOLFOXIRI plus bevacizumab may be regarded as a preferred first-line treatment option forclinically selected patients with right-sided metastatic colorectal cancer irrespective of their RASand BRAF mutational status

In left-sided tumors, the benefit from the intensification of the chemotherapy backbone appearsless pronounced, thus leading to consider doublets plus an anti-EGFR as a preferred option inRAS and BRAF wild-type patients.

M. Geissler et al. ESMO 2017 # 4750

VOLFI

MANTENIMIENTO

Inducción Mantenimiento Objetivo

MACRO Xelox x 6 c +Bev -Xelox-Bev

-Bevacizumab

No Inf.

PFS

-

STOP and GO Xelox x 6 c+ Bev -Xelox-Bev

-Xeloda-Bev

PFS +

CAIRO 3 Xelox x 6 c + Bev -Observación

-Xeloda*-Bev

PFS2 +

AIO 0207 Fu+Oxaliplatino+Bev 6 m -Observación

-Bev

-Fu+Bev

No inf.

TFS+/-

SAKK 41/06 QT+Bev x 4-6 m -Observación

- Bevacizumab

No Inf.

TTP

-

PRODIGE 9 Folfiri-Beva x 6 m -Observación

-Bevacizumab

TCD -

OPTIMOX3 QT + Beva x 3 m -Bevacizumab

- Erlotinib-Bev

PFS +

NORDIC ACT QT + Beva x 18 s -Bevacizumab

- Erlotinib-Bev

PFS -

Con Bevacizumab

• Patients receiving FOLFOX or CAPOX plus bevacizumab- based therapy as induction therapy should be considered

for maintenance therapy after 6 cycles of CAPOX and 8 cycles of FOLFOX. The optimal maintenance treatment is

a combination of a fluoropyrimidine plus bevacizumab .

• Patients receiving FOLFIRI can continue on induction therapy—at a minimum—for as long as tumour shrinkage

continues and the treatment is tolerable.

• For patients receiving initial therapy with FOLFOXIRI plus or minus bevacizumab, a fluoropyrimidine plus

bevacizumab may be considered as maintenance therapy

¿Tumor primario no resecado?

¿Afectación peritoneal?

Enfermedad voluminosa/sintomática

¿MANTENIMIENTO EN LO PACIENTES TRATADOS EN

PRIMERA LÍNEA CON AC-AntiEGFR?

Con Ac-AntiEGFR

MACRO-2

ASCOGI 2018 # 729

Slide 4

Presented By Filippo Pietrantonio at 2018 ASCO Annual Meeting

Slide 11

Slide 12

Presented By Daniele Rossini at 2018 ASCO Annual Meeting

Christine M. Parseghian. ASCO 2018# 3511

SEGUNDA LÍNEA

RAS MUTADO

1ª LÍNEA QT (doblete) + Antiangiogénico

2ª LÍNEA QT + Antiangiogénico

COLON DERECHO E IZQUIERDO

1ª LÍNEA QT (TRIPLETE) + Antiangiogénico

MANTENIMIENTO

TIEMPO PROGRESIÓN

TOXICIDADES

¿ DOBLETE + ANTIANGIOGÉNICO?

Racional Biológico

Loupakis, F. et al BJC 2011Kopetz S. et al. JCO 2010

ASCOGI-2017

¿OTRAS OPCIONES EN LA SECUENCIA?

Presented By Howard Hochster at 2018 ASCO Annual Meeting

1º OBJ

COLON IZQUIERDO

1ª LÍNEA QT + Anti-EGFR

2ª LÍNEA QT + Antiangiogénico

1ª LÍNEA QT + Antiangiogénico

2ª LÍNEA QT + Antiangiogénico

3ª LÍNEA AntiEGFR +/- QT

COLON DERECHO

1ª LÍNEA QT + Antiangiogénico

2ª LÍNEA QT + AntiEGFR

RAS NATIVO

RESPUESTA

1ª LÍNEA QT + Anti-EGFR

2ª LÍNEA QT +

Antiangiogénico

RESPUESTA

DATOS PRE-CLÍNICOS

SECUENCIA RAS NATIVO: AntiEGFR Antiangiogénico

It seems that the sequential application of anti- EGFR agents followed by second-line anti-

VEGF therapy achieves more favorable results than the reverse sequence.

SECUENCIA RAS NATIVO: AntiEGFR Antiangiogénico

DATOS DE ENSAYOS CLÍNICOS

ASCO 2017 # 3525. D. P. Modest

Dan Aderka. WCGI 2018

¿EN QUE MOMENTO DEL “CONTINUUM OF CARE”?

Presented By Katherine Clifton at 2018 ASCO Annual Meeting

Slide 32

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