Overall survival with frontline vs subsequent anti-epidermal growth factor receptor therapies in unresectable, RAS/BRAF wild-type, left-sided metastatic colorectal cancer.

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.