CONTINUM ASISTENCIAL: FACTORES DE DECISIÓN. Ana Mª López Muñoz Hospital Universitario de Burgos

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1 CONTINUM ASISTENCIAL: FACTORES DE DECISIÓN Ana Mª López Muñoz Hospital Universitario de Burgos

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

3 The use of novel therapies and more complex treatment strategies have contributed to progressively increase the median life expectancy Additional complexities Additional opportunities

4 PACIENTE Edad PS Comorbilidad Preferencias Socio-económicos TUMOR Aspectos moleculares Localización Volumen tumoral Temporalidad TRATAMIENTO Perfil eficacia Toxicidad Disponibilidad

5 Assessment of clinical condition of the patient E. Van Cutsem et al. Annals of Oncology 2016; 27:

6 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

7 PHASE III AVEX D. Cunninghan et al. Lancet Oncology 2013 PHASE II TASCO1 E. V. Cutsem. WCGI 2018

8 OBJETIVO 8

9 TRATAMIENTO Fármacos aprobados para el tratamiento del CCRm: Fluoropirimidinas, Oxaliplatino, Irinotecan, Panitumumab, Cetuximab, Bevacizumab, Aflibercept, Ramucirumab, Regorafenib y TAS 102. (MSI (FDA): Pembrolizumab y Nivolumab) 1. EFICACIA 2. TOXICIDAD BIOMARCADORES 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/m 2 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]

10 TUMOR NCCN Guidelines Version Colon Cancer 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

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14 SIDENESS

15 ALGUNA NUEVA CONSIDERACIÓN CUANDO EL OBJETIVO ES LA CITORREDUCCIÓN?

16 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 for clinically selected patients with right-sided metastatic colorectal cancer irrespective of their RAS and BRAF mutational status In left-sided tumors, the benefit from the intensification of the chemotherapy backbone appears less pronounced, thus leading to consider doublets plus an anti-egfr as a preferred option in RAS and BRAF wild-type patients. C. Cremollini et al. Annals of Oncology 2018

17 VOLFI M. Geissler et al. ESMO 2017 # 4750

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20 MANTENIMIENTO

21 Con Bevacizumab Inducción Mantenimiento Objetivo MACRO Xelox x 6 c +Bev -Xelox-Bev -Bevacizumab STOP and GO Xelox x 6 c+ Bev -Xelox-Bev -Xeloda-Bev CAIRO 3 Xelox x 6 c + Bev -Observación -Xeloda*-Bev AIO 0207 Fu+Oxaliplatino+Bev 6 m -Observación -Bev -Fu+Bev SAKK 41/06 QT+Bev x 4-6 m -Observación - Bevacizumab PRODIGE 9 Folfiri-Beva x 6 m -Observación -Bevacizumab OPTIMOX3 QT + Beva x 3 m -Bevacizumab - Erlotinib-Bev NORDIC ACT QT + Beva x 18 s -Bevacizumab - Erlotinib-Bev No Inf. PFS - PFS + PFS2 + No inf. TFS No Inf. TTP +/- - TCD - PFS + PFS -

22 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

23 MANTENIMIENTO EN LO PACIENTES TRATADOS EN PRIMERA LÍNEA CON AC-AntiEGFR?

24 MACRO-2 Con Ac-AntiEGFR

25 ASCOGI 2018 # 729

26 Slide 4 Presented By Filippo Pietrantonio at 2018 ASCO Annual Meeting

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29 Presented By Daniele Rossini at 2018 ASCO Annual Meeting

30 Christine M. Parseghian. ASCO 2018# 3511

31 SEGUNDA LÍNEA

32 RAS MUTADO COLON DERECHO E IZQUIERDO 1ª LÍNEA QT (doblete) + Antiangiogénico 1ª LÍNEA QT (TRIPLETE) + Antiangiogénico 2ª LÍNEA QT + Antiangiogénico MANTENIMIENTO TIEMPO PROGRESIÓN TOXICIDADES DOBLETE + ANTIANGIOGÉNICO?

33 Racional Biológico Kopetz S. et al. JCO 2010 Loupakis, F. et al BJC 2011 ASCOGI-2017

34 OTRAS OPCIONES EN LA SECUENCIA?

35 Presented By Howard Hochster at 2018 ASCO Annual Meeting

36 1º OBJ

37 COLON IZQUIERDO RAS NATIVO 1ª LÍNEA QT + Anti-EGFR 2ª LÍNEA QT + Antiangiogénico COLON DERECHO RESPUESTA 1ª LÍNEA QT + Antiangiogénico 1ª LÍNEA QT + Antiangiogénico 1ª LÍNEA QT + Anti-EGFR 2ª LÍNEA QT + Antiangiogénico 2ª LÍNEA QT + AntiEGFR 2ª LÍNEA QT + Antiangiogénico 3ª LÍNEA AntiEGFR +/- QT RESPUESTA

38 SECUENCIA RAS NATIVO: AntiEGFR Antiangiogénico DATOS PRE-CLÍNICOS

39 SECUENCIA RAS NATIVO: AntiEGFR Antiangiogénico DATOS DE ENSAYOS CLÍNICOS 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.

40 ASCO 2017 # D. P. Modest

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48 Dan Aderka. WCGI 2018

49 EN QUE MOMENTO DEL CONTINUUM OF CARE?

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51 Presented By Katherine Clifton at 2018 ASCO Annual Meeting

52 Slide 32

53 pero más fascinante

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