Anti-EGFR re-challenge with chemotherapy in RAS wild-type advanced colorectal cancer (A-REPEAT study): efficacy and correlations with tissue and plasma genotyping

Abstract

Background

Approved treatments for colorectal cancer (CRC) patients pretreated with two lines of therapy are of limited efficacy. Anti-epidermal growth factor receptor (EGFR) re-challenge might represent an option in RAS wild-type tumours. This study aimed to evaluate the efficacy of anti-EGFR re-challenge strategies (panitumumab/chemotherapy).

Materials and methods

RAS wild-type metastatic CRC patients following first-line chemotherapy + anti-EGFR agent and second-line chemotherapy ± anti-vascular endothelial growth factor agent were eligible. Panitumumab with irinotecan or oxaliplatin-based chemotherapy was used. The primary objective was response rate (RR). Secondary objectives were safety, progression-free survival and overall survival. Next-generation sequencing-based genotyping in archived tissue and plasma was carried out to identify prognostic factors.

Results

The study closed prematurely, due to poor accrual, with 23 patients included. Most patients had primary tumours in the left colon/rectum, and the liver was the most common metastatic site. Treatment modifications were required in 74% of patients due to side-effects primarily, neutropenia and acneiform rash. One patient died from hepatic failure. The objective RR in the intention-to-treat population was 13%, and the disease control rate (DCR) was 52%. Forty-eight percent of patients tested via liquid biopsy had RAS mutations before re-challenge with panitumumab despite a median interval from previous anti-EGFR therapy of 12 months. Control of disease did not correlate with the results of liquid biopsy. RR and DCR in patients without RAS mutations in liquid biopsies were 18.2% and 54.5%, respectively.

Conclusion

Panitumumab/chemotherapy as an anti-EGFR re-challenge strategy had modest activity in our patient cohort.