Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Mar 24, 2025; 16(3): 102076
Published online Mar 24, 2025. doi: 10.5306/wjco.v16.i3.102076
Overall survival with frontline vs subsequent anti-epidermal growth factor receptor therapies in unresectable, RAS/BRAF wild-type, left-sided metastatic colorectal cancer
Nussara Pakvisal, Richard M Goldberg, Chirawadee Sathitruangsak, Witthaya Silaphong, Satawat Faengmon, Nattaya Teeyapun, Chinachote Teerapakpinyo, Suebpong Tanasanvimon
Nussara Pakvisal, Witthaya Silaphong, Satawat Faengmon, Nattaya Teeyapun, Suebpong Tanasanvimon, Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
Richard M Goldberg, Department of Medicine, WVU Cancer Institute, West Virginia University, Morgantown, WV 26506, United States
Chirawadee Sathitruangsak, Medical Oncology Unit, Division of Internal Medicine, Faculty of Medicine, Holistic Center for Cancer Study and Care (HOCC-PSU) and Prince of Songkla University, Songkhla 90110, Thailand
Chinachote Teerapakpinyo, Chulalongkorn GenePRO Center, Research Affairs, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
Author contributions: Pakvisal N, Goldberg RM, Sathitruangsak C and Tanasanvimon S conceived and designed the study; Pakvisal N, Sathitruangsak C, Silaphong W, Faengmon S, Teeyapun N and Teerapakpinyo C performed data collection; Pakvisal N performed statistical analysis; Pakvisal N, Goldberg RM and Tanasanvimon S wrote the first draft of the manuscript. All authors contributed to the data interpretation. All the authors revised and edited the final manuscript.
Institutional review board statement: This study was reviewed and approved by the International Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand (No. 0375/66).
Informed consent statement: A waiver of informed consent was granted by the Ethics Committee.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: The datasets analyzed during the study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Suebpong Tanasanvimon, MD, Assistant Professor, Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, 1873 RAMA IV Road, Bangkok 10330, Thailand. surbpong@yahoo.com
Received: October 7, 2024
Revised: November 25, 2024
Accepted: December 12, 2024
Published online: March 24, 2025
Processing time: 105 Days and 13.2 Hours
Abstract
BACKGROUND

The combination of anti-epidermal growth factor receptor (EGFR) therapy and chemotherapy is currently a preferred first-line treatment for patients with unresectable, RAS and BRAF wild-type, left-sided metastatic colorectal cancer (mCRC). Several studies have also demonstrated the benefit of anti-EGFR therapy in subsequent line settings for this patient population. However, direct evidence comparing the effectiveness of frontline vs subsequent anti-EGFR therapy remains limited, leaving a crucial gap in guiding optimal treatment strategies.

AIM

To compare overall survival (OS) between frontline and subsequent anti-EGFR treatment in patients with unresectable, RAS and BRAF wild-type, left-sided mCRC.

METHODS

We retrospectively reviewed the medical records of mCRC patients treated at The King Chulalongkorn Memorial Hospital and Songklanagarind Hospital, Thailand, between January 2013 and April 2023. Patients were classified into two groups based on the sequence of their anti-EGFR treatment. The primary endpoint was OS.

RESULTS

Among 222 patients with a median follow-up of 29 months, no significant difference in OS was observed between the frontline and subsequent-line groups (HR 1.03, 95%CI: 0.73-1.46, P = 0.878). The median OS was 35.53 months (95%CI: 26.59-44.47) for the frontline group and 31.60 months (95%CI: 27.83-35.37) for the subsequent-line group. In the subsequent-line group, 71 patients (32.4%) who ultimately never received anti-EGFR therapy had a significantly worse median OS of 19.70 months (95%CI: 12.87-26.53).

CONCLUSION

Frontline and subsequent-line anti-EGFR treatments provide comparable OS in unresectable, RAS/BRAF wild-type, left-sided mCRC patients, but early exposure is vital for those unlikely to receive subsequent therapy.

Keywords: Metastatic colorectal cancer; Anti-epidermal growth factor receptor; Frontline; Subsequent line; RAS wild-type metastatic colorectal cancer; BRAF wild-type metastatic colorectal cancer; Left-sided metastatic colorectal cancer; Overall survival

Core Tip: Anti-epidermal growth factor receptor (EGFR) therapy improves survival in RAS/BRAF wild-type metastatic colorectal cancer, whether used in frontline or subsequent settings. No direct evidence demonstrates frontline treatment’s superiority, particularly in unresectable, left-sided tumors. Our study found no significant difference in overall survival between these approaches, suggesting timing does not affect overall survival if anti-EGFR therapy is administered. However, omitting frontline anti-EGFR risks some patients losing the chance to benefit later. These findings highlight the importance of early exposure and offer valuable guidance for optimizing treatment sequencing in this patient population.