CRC treatment guidelines Guidelines for the treatment of

Introduction • This slide deck summarises the recommended treatment pathways provided by ESMO and

ESMO consensus guidelines Summary of management guidelines for patients with metastatic colorectal cancer 1.

Zurich treatment algorithm Ch. T, chemotherapy; EGFR, epidermal growth factor receptor; FP, fluoropyrimidine; mt,

Systematic therapy choices for patients with unresectable metastatic disease *If not previously given. Based

NCCN Clinical Practice Guidelines Treatment considerations for advanced colon and rectal cancers 1. NCCN

Subsequent treatment considerations for advanced colon and rectal cancers Treatment of advanced CRC should

Summary • ESMO and NCCN guidelines aim to provide guidelines for the diagnosis, treatment

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CRC: treatment guidelines Guidelines for the treatment of advanced colon and rectal cancers 1. NCCN Clinical Practice Guideline in Oncology. Rectal Cancer, Version 1. 2020; 2. NCCN Clinical Practice Guideline in Oncology. Colon Cancer, Version 1. 2020; 3. Van Cutsem E, et al. Ann Oncol 2016; 27(8): 1386– 422.

Introduction • This slide deck summarises the recommended treatment pathways provided by ESMO and NCCN for locally advanced or metastatic CRC, which includes rectal and colon cancers 1– 3 • Please refer to the full guidelines for more information on: – Diagnostic work-up and follow-up – Treatment of early- and intermediate-stage disease – Details of specific treatment regimens CRC, colorectal cancer; ESMO, European Society for Medical Oncology; NCCN, National Comprehensive Cancer Network. 1. NCCN Clinical Practice Guideline in Oncology. Rectal Cancer, Version 1. 2020; 2. NCCN Clinical Practice Guideline in Oncology. Colon Cancer, Version 1. 2020; 3. Van Cutsem E, et al. Ann Oncol 2016; 27(8): 1386– 422.

ESMO consensus guidelines Summary of management guidelines for patients with metastatic colorectal cancer 1. Van Cutsem E, et al. Ann Oncol 2016; 27(8): 1386– 422.

Zurich treatment algorithm Ch. T, chemotherapy; EGFR, epidermal growth factor receptor; FP, fluoropyrimidine; mt, mutant; OMD, oligometastatic disease; VEGF, vascular endothelial growth factor; WT, wild-type. 1. Van Cutsem E, et al. Ann Oncol 2016; 27(8): 1386– 422.

Systematic therapy choices for patients with unresectable metastatic disease *If not previously given. Based on the Zurich treatment algorithm; excluding patients with OMD. Treatment decisions at each stage should consider patient suitability, tolerability, and prior exposure to targeted agents. Ch. T, chemotherapy; EGFR, epidermal growth factor receptor; FC, 5 -fluorouracil and cisplatin; FOLFIRI, folinic acid, fluorouracil, irinotecan; FOLFOXIRI, folinic acid, fluorouracil, oxaliplatin, irinotecan; FP, fluoropyrimidine; mt, mutant; OMD, oligometastatic disease; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; WT, wild-type. 1. Van Cutsem E, et al. Ann Oncol 2016; 27(8): 1386– 422.

NCCN Clinical Practice Guidelines Treatment considerations for advanced colon and rectal cancers 1. NCCN Clinical Practice Guideline in Oncology. Rectal Cancer, Version 1. 2020; 2. NCCN Clinical Practice Guideline in Oncology. Colon Cancer, Version 1. 2020.

Subsequent treatment considerations for advanced colon and rectal cancers Treatment of advanced CRC should be considered as a continuum of care. Decision-making at each stage of therapy should account for patient suitability and tolerability, tumour biomarkers, and prior exposure to chemotherapies and/or targeted agents Initial systemic therapy: Is the patient considered appropriate for intensive therapy? Consider the patient’s prior treatments. Have they received a previous: - Oxaliplatin-based chemotherapy? - Irinotecan-based chemotherapy? - Oxaliplatin- and irinotecan-based regimen? - FP without oxaliplatin/irinotecan? Consider the results of molecular testing. Is the patient’s tumour: - KRAS/NRAS/BRAF wild-type? - HER 2 -amplified, RAS wild-type? - BRAF V 600 E-positive? - d. MMR/MSI-H? Please refer to the NCCN treatment guidelines for full details of the decision-making pathway and treatment options at each stage. BRAF, B rapidly accelerated fibrosarcoma; d. MMR, deficient mismatch repair; FP, fluoropyrimidine; KRAS, Kirsten rat sarcoma; MSI-H, high levels of microsatellite instability; NCCN, National Comprehensive Cancer Network; NRAS, neuroblastoma rat sarcoma; RAS, rat sarcoma. 1. NCCN Clinical Practice Guideline in Oncology. Rectal Cancer, Version 1. 2020; 2. NCCN Clinical Practice Guideline in Oncology. Colon Cancer, Version 1. 2020.

Summary

Summary • ESMO and NCCN guidelines aim to provide guidelines for the diagnosis, treatment and follow-up of CRC based on the findings of evidence-based medicine • Both sets of guidelines provide specific treatment recommendations for patients with defined molecular markers (including RAS, BRAF, MSI and HER 2) • Management of CRC can be considered a ‘continuum of care’, and treatment decisions at each stage should take into account the patient’s clinical status and treatment goals CRC, colorectal cancer; ESMO, European Society for Medical Oncology; HER 2, human epidermal growth factor receptor 2; MSI, microsatellite instability; NCCN, National Comprehensive Cancer Network. 1. Van Cutsem E, et al. Ann Oncol 2016; 27(8): 1386– 422.