Is there a role for rechallenge and reintroduction of anti-EGFR plus chemotherapy in later lines of therapy for metastatic colorectal carcinoma? A retrospective analysis

Background: Mechanisms of resistance have been described during disease progression (PD) for patients under treatment with anti-EGFR plus chemotherapy (CT). The aim of our study was to evaluate efficacy of a nti-EGFR rechallenge (ReCH) and reintroduction (Rein) in metastatic colorectal cancer (mCRC). Materials and methods: This is a retrospective analysis of patients with mCRC that previously received anti-EGFR + CT and interrupted therapy due to PD in the ReCH group and other reasons in the Reln group. We aimed to describe progression-free survival (PFS), overall survival (OS) and response rate (RR) after re-exposure and to evaluate prognostic factors associated with PFS. Results: Sixty-eight patients met the inclusion criteria. The median follow-up after reexposure was 39.3 months. ReCH was adopted in 25% and Reln in 75%. The median antiEGFR free interval was at 10.5 months. At re-exposure, the main CT regimen was FOLFIRI in 58.8%. Cetuximab and Panitumumab were used in 59 and 9 patients, respectively. mPFS for ReCH and Reln was 3.3 x 8.4 months, respectively (p 0.001). The objective response rate for ReCH and Reln was 18% and 52%, respectively. In univariate analysis, adverse prognostic factors related to PFS were: stable disease or PD at first anti-EGFR exposure (HR: 2.12, CI:1.20-3.74; p = 0.009); ReCH (HR: 3.44, CI:1.88-6.29, p < 0.0001); rechallenge at fourth or later lines (HR: 2.51, CI:1.49-4.23, p = 0.001); panitumumab use (HR: 2.26 CI:1.18-5.54, p = 0.017). In the multivariate model, only ReCH remained statistically significant (HR = 2.63, CI: 1.14-6.03, p = 0.022). Conclusion: In our analysis, ReCH resulted in short PFS and low RR. However, reintroduction of anti-EGFR plus CT before complete resistance arose resulted in prolonged PFS. These data could be clinically useful to guide a treatment break due to side effects or patient decisions. Our data should be confirmed by larger and prospective trials.