Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer

Abstract

The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with metastatic colorectal cancer (mCRC), published in late 2022, were adapted in December 2022, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with mCRC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with mCRC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), co-ordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian countries. The latter are discussed separately in the manuscript. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with mCRC across the different countries of Asia, drawing on the evidence provided by both Western and Asian trials, whilst respecting the differences in screening practices, molecular profiling and age and stage at presentation, coupled with a disparity in the drug approvals and reimbursement strategies, between the different countries.

Keywords: ESMO; Pan-Asian; guidelines; metastatic colorectal cancer; treatment.

Figure 1

Local treatment of CRC metastases. Purple box: general categories or stratification; orange box: surgery; dark green boxes: radiotherapy; blue boxes: systemic anticancer therapy; white boxes: other aspects of management. HAIC, hepatic arterial infusion chemotherapy; mCRC, metastatic colorectal cancer; SBRT, stereotactic body radiotherapy; SIRT, selective internal radiotherapy; TACE, transarterial chemoembolisation; TARE, transarterial radioembolisation. ^aIn patients with unresectable colorectal liver metastases only, or oligometastatic disease (OMD) in the liver, thermal ablation (TA) can be considered for small metastases [III, B]. In patients with lung-only metastases or OMD including lung lesions, TA may be considered along with resection, according to tumour size, number, location, the extent of lung parenchyma loss, comorbidity, or other factors [III, B].

Figure 2

Management of stage IV unresectable mCRC in first-line therapy. Purple box: general categories or stratification; blue boxes: systemic anticancer therapy; white boxes: other aspects of management. 5-FU, 5-fluorouracil; ChT, chemotherapy; dMMR, deficient mismatch repair; EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; MCBS, ESMO-Magnitude of Clinical Benefit Scale; FOLFOX, 5-FU–LV–oxaliplatin; FOLFOXIRI, FOLFOX plus irinotecan; mCRC, metastatic colorectal cancer; MSI-H, microsatellite instability-high; mut, mutant; PD, progressive disease; S-1, tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate; wt, wild-type. ^aIn patients presenting with cardiotoxicity and/or hand-foot syndrome on 5-FU or capecitabine-based ChT, S-1 may be used as an alternative [III, B]. ^bAdditional details on treatments and drug combinations can be found under ‘Management of advanced and metastatic disease without potential conversion: first-line and second-line treatment’. ^cIn frail or elderly patients unable to tolerate ChT whose tumours are left-sided and RAS wt. ^dCetuximab–FOLFIRI ESMO-MCBS v1.1 score: 4; panitumumab–FOLFOX4 ESMO-MCBS v1.1 score: 4; panitumumab–modified FOLFOX6 ESMO-MCBS v1.1 score: 3.^{h e}Panitumumab–FOLFOX4 ESMO-MCBS v1.1 score: 4; panitumumab–modified FOLFOX6 ESMO-MCBS v1.1 score: 3; for cetuximab–FOLFIRI ESMO-MCBS v1.1 score: 4.^{h f}In a very selected population. ^gA triplet with FOLFOXIRI plus bevacizumab is an option for selective patients with good performance status and without comorbidities [I, B; ESMO-MCBS v1.1 score: 2].^{h h}ESMO-MCBS v1.1 score for new therapy/indication approved by the EMA since 1 January 2016. The score has been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee. ⁱESCAT scores apply to genomic alterations only. These scores have been defined by the guideline authors and validated by the ESMO Translational Research and Precision Medicine Working Group. See Supplementary Table S3, available at https://doi.org/10.1016/j.esmoop.2023.101558 for more information on ESCAT.

Figure 3

Management of stage IV unresectable mCRC with maintenance therapy. Purple boxes: general categories or stratification; blue boxes and mauve box: systemic anticancer therapy; white boxes: other aspects of management. 5-FU, fluorouracil; ChT, chemotherapy; EGFR, epidermal growth factor receptor; FOLFIRI, folinic acid–fluorouracil–irinotecan; mCRC, metastatic colorectal cancer; PD, progressive disease; S-1, tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate. ^aIn patients presenting with cardiotoxicity and/or hand-foot syndrome on 5-FU- or capecitabine-based ChT, S-1 may be used as an alternative [III, B]. ^bDue to the lack of a cumulative toxicity of FOLFIRI.

Figure 4

Management of stage IV unresectable mCRC in the second line. Purple boxes: general categories or stratification; blue boxes: systemic anticancer therapy; white boxes: other aspects of management. 5-FU, fluorouracil; CAPOX, capecitabine–oxaliplatin; ChT, chemotherapy; EGFR, epidermal growth factor receptor; dMMR, deficient mismatch repair; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; FOLFIRI, folinic acid–fluorouracil–irinotecan; FOLFOX, folinic acid–fluorouracil–oxaliplatin; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mCRC, metastatic colorectal cancer; MSI-H, microsatellite instability-high; mut, mutant; PD, progressive disease; S-1, tegafur, 5-chloro-2, 4-dihydroxypyridine and potassium oxonate; wt, wild-type. ^aIn patients presenting with cardiotoxicity and/or hand-foot syndrome on 5-FU- or capecitabine-based ChT, S-1 may be used as an alternative [III, B]. ^bESMO-MCBS v1.1 score for new therapy/indication approved by the EMA since 1 January 2016. The score has been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee. ^cFOLFOX or CAPOX, if no contraindications. ^dBevacizumab can be combined with a ChT doublet (a fluoropyrimidine with oxaliplatin or irinotecan, depending on the previous first-line ChT backbone) [I, A; ESMO-MCBS v1.1 score: 1]. ^eWith or without previous first-line treatment with bevacizumab and independent of RAS mutational status and primary tumour location. ^fESCAT scores apply to genomic alterations only. These scores have been defined by the guideline authors and validated by the ESMO Translational Research and Precision Medicine Working Group. See Supplementary Table S3, available at https://doi.org/10.1016/j.esmoop.2023.101558 for more information on ESCAT scores. ^gIndicated for immunotherapy-naive patients.

Figure 5

Management of stage IV unresectable mCRC in third- and later-line therapy. Purple box: general categories or stratification; blue boxes: systemic anticancer therapy; white boxes: other aspects of management. EGFR, epidermal growth factor receptor; EMA, European Medicines Agency; ESCAT, ESMO Scale for Clinical Actionability of Molecular Targets; FDA, Food and Drug Administration; HER2, human epidermal growth factor receptor 2; mAb, monoclonal antibody; MCBS, ESMO-Magnitude of Clinical Benefit Scale; mCRC, metastatic colorectal cancer; mut, mutant; PD, progressive disease; wt, wild-type. ^aFor a summary of recommended anti-HER2 regimens for mCRC see Supplementary Table S4, available at https://doi.org/10.1016/j.esmoop.2023.101558. ^bESCAT scores apply to genomic alterations only. These scores have been defined by the guideline authors and validated by the ESMO Translational Research and Precision Medicine Working Group. See Supplementary Table S3, available at https://doi.org/10.1016/j.esmoop.2023.101558 for more information on ESCAT scores. ^cIn RAS wt patients not previously treated with anti-EGFR monoclonal antibodies. ^dESMO-MCBS v1.1 score for new therapy/indication approved by the EMA since 1 January 2016. The score has been calculated by the ESMO-MCBS Working Group and validated by the ESMO Guidelines Committee. ^eTreatment for BRAF-mut patients if not used in the second line. ^fNot EMA or FDA approved.