Updated treatment recommendation for third-line treatment in advanced colorectal cancer from the ESMO Metastatic Colorectal Cancer Living Guideline

The following European Society for Medical Oncology (ESMO) Living Guideline has been recently updated with new treatment recommendations: ESMO Metastatic Colorectal Cancer Living Guideline.1Cervantes A. Adam R. Rosello S. et al.Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.Ann Oncol. 2023; 34: 10-32Abstract Full Text Full Text PDF PubMed Scopus (190) Google Scholar,2ESMO Metastatic Colorectal Cancer Living Guideline, v1.1 July 2023.https://www.esmo.org/living-guidelines/esmo-metastatic-colorectal-cancer-living-guidelineDate accessed: October 5, 2023Google Scholar View the ESMO Metastatic Colorectal Cancer Living Guideline here: https://www.esmo.org/living-guidelines/esmo-metastatic-colorectal-cancer-living-guideline. In the SUNLIGHT phase III trial, trifluridine–tipiracil–bevacizumab improved both progression-free survival [hazard ratio (HR) 0.44, 95% confidence interval (CI) 0.36-0.54, P < 0.001] and overall survival (HR 0.61, 95% CI 0.49-0.77, P < 0.001) in patients with metastatic colorectal cancer (mCRC) over monotherapy with trifluridine–tipiracil.3Prager G.W. Taieb J. Fakih M. et al.Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer.N Engl J Med. 2023; 388: 1657-1667Crossref PubMed Scopus (22) Google Scholar Patients included in this study had received no more than two previous chemotherapy regimens for the treatment of mCRC and had progressive disease or had experienced unacceptable adverse effects (AEs) from their most recent regimen. Previous treatment must have included a fluoropyrimidine, irinotecan, oxaliplatin, an anti-vascular endothelial growth factor monoclonal antibody (mAb) or an anti-epidermal growth factor receptor mAb, and the treatment could have included neoadjuvant or adjuvant chemotherapy if disease had recurred during treatment or within 6 months after the last administration of neoadjuvant or adjuvant therapy. Severe AEs (grade ≥3) were reported in 72.4% of the patients in the trifluridine–tipiracil–bevacizumab group and in 69.5% of the patients in the trifluridine–tipiracil group. The most common AEs in both groups were neutropenia, nausea and anaemia. AEs that were more frequent in the trifluridine–tipiracil–bevacizumab group than in the trifluridine–tipiracil group were hypertension (10.2% versus 2.0%), nausea (37.0% versus 27.2%) and neutropenia (62.2% versus 51.2%), including severe (grade ≥3) neutropenia (43.1% versus 32.1%, respectively). AEs leading to discontinuation of treatment were similar in both arms of the trial. No treatment-related deaths were reported. Furthermore, Eastern Cooperative Oncology Group performance status deterioration was 9.3 months in the trifluridine–tipiracil–bevacizumab group and 6.3 months in the trifluridine–tipiracil group (HR 0.54, 95% CI 0.43-0.67). Trifluridine–tipiracil–bevacizumab was recently approved by the European Medicines Agency (EMA) and obtained an ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) v1.1 score of 4, which indicates substantial clinical benefit. Figure 1 provides an updated treatment algorithm. •Trifluridine–tipiracil–bevacizumab is recommended in patients pretreated with fluoropyrimidines, oxaliplatin, irinotecan and biologics, or in earlier lines of therapy following oxaliplatin and irinotecan regimen failure [I, A; ESMO-MCBS v1.1 score: 4]. ESMO-MCBS v1.14Cherny N.I. Dafni U. Bogaerts J. et al.ESMO-Magnitude of Clinical Benefit Scale version 1.1.Ann Oncol. 2017; 28: 2340-2366Abstract Full Text Full Text PDF PubMed Scopus (395) Google Scholar was used to calculate scores for new therapies/indications approved by the EMA or Food and Drug Administration (https://www.esmo.org/Guidelines/ESMO-MCBS). The scores have been calculated and validated by the ESMO-MCBS Working Group and reviewed by the authors. Manuscript editing support was provided by Claire Bramley (ESMO Guidelines staff); this support was funded by ESMO. Nathan Cherny, Chair of the ESMO-MCBS Working Group, Urani Dafni, ESMO-MCBS Working Group Member/Frontier Science Foundation Hellas, and Giota Zygoura of Frontier Science Foundation Hellas provided review and validation of the ESMO-MCBS scores. Nicola Latino (ESMO Scientific Affairs staff) provided coordination and support of the ESMO-MCBS scores. No external funding has been received for the preparation of this ESMO Living Guideline update. Production costs have been covered by ESMO from central funds.