Abstract
BackgroundMechanisms 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 anti-EGFR rechallenge (ReCH) and reintroduction (ReIn) in metastatic colorectal cancer (mCRC).Materials and methodsThis 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 ReIn 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.ResultsSixty-eight patients met the inclusion criteria. The median follow-up after re-exposure was 39.3 months. ReCH was adopted in 25% and ReIn in 75%. The median anti-EGFR 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 ReIn was 3.3 × 8.4 months, respectively (p 0.001). The objective response rate for ReCH and ReIn 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).ConclusionIn 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.
Highlights
Colorectal cancer is a leading cause of cancer-related death [1]
Adverse prognostic factors related to progression-free survival (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 our analysis, ReCH resulted in short PFS and low response rate (RR)
Summary
Colorectal cancer is a leading cause of cancer-related death [1]. Approximately 25% of all colon cancer patients will have advanced disease at diagnosis and almost 50% will eventually recur during the course of their disease [2]. Progress in systemic treatment seen in recent years has resulted in prolonged survival for patients with metastatic disease [2]. EGFR pathway plays an important role driving cancer cell growth and survival [3]. 60% of metastatic colorectal cancer (mCRC) tumors develop mutations in the EGFR pathway (mainly KRAS/NRAS/BRAF) which will lead to a constitutively downstream activation and primary resistance to anti-EGFR agents [4]. Large phase 3 trials demonstrated that first-line anti-EGFR agents (cetuximab and panitumumab) plus standard chemotherapy (FOLFOX and FOLFIRI) induced objective responses in about 60% of patients. 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 anti-EGFR rechallenge (ReCH) and reintroduction (ReIn) in metastatic colorectal cancer (mCRC)
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