Anti-EGFR Reintroduction and Rechallenge in Metastatic Colorectal Cancer (mCRC): A Real-World Analysis

SIMPLE SUMMARY: Colorectal carcinoma (CRC) is one of the most prevalent malignomas worldwide and a leading cause of cancer associated mobidity and mortality. While screening and therapeutic developments have improved long-term survival and cure rates, a considerable fraction of patients suffers disease progression and death. Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) are amongst the cornerstones of therapy in advanced-stage CRC. However, while prospective clinical trials have confirmed the benefit of including those agents into the regimes for advanced CRC, disease progression or therapy-related toxicities might require physicians to switch from anti-EGFR-based therapies to alternative treatments. With limiting options in later treatment lines however, re-exposure to anti-EGFR-based therapy regimes is a valuable option and evidence for this approach is limited. This real-world study from a large oncology center in germany includes data from more than 500 patients to underscore the benefit of anti-EGFR re-exposure in patients with advanced CRC. ABSTRACT: Background and Aims: In patients with Rat sarcoma proto-oncogene (RAS) wild-type metastatic colorectal cancer (mCRC), anti-epidermal growth factor receptor (EGFR) antibodies have been established in first- and further therapy lines. Due to limited treatment options upon disease progression, anti-EGFR re-exposure is increasingly employed in real-world oncology. The aim of this study was to assess clinical implementation and utility of anti-EGFR retreatment strategies in real-world mCRC patients. Methods: In this monocentric retrospective study, we included 524 patients with CRC and identified patients who received an anti-EGFR-based treatment as well as anti-EGFR rechallenge (progression on first-line anti-EGFR therapy) or reintroduction (discontinuation due to intolerance/toxicity/other). Results: In total, 143 patients received an anti-EGFR-based first- or second-line treatment, showing a similar overall survival (OS) compared to the non-anti-EGFR treatment group (38.3 vs. 39.6 months, p = 0.88). Thirty-three patients met the inclusion criteria for anti-EGFR re-exposure and were either assigned to rechallenge (n = 21) or reintroduction (n = 12) subgroups. The median FU after re-exposure was 45.8 months. Cetuximab and Panitumumab were used in 21 and 12 patients, respectively, and the main chemotherapy at re-exposure was FOLFIRI in 39.4%. Anti-EGFR re-exposure was associated with a distinct trend towards a better outcome (median OS 56.0 vs. 35.4 months, p = 0.06). In a subgroup comparison, reintroduction was associated with a higher OS and PFS in trend compared to the rechallenge (mOS 66 vs. 52.4, n.s., mPFS 7.33 vs. 3.68 months, n.s.). Conclusions: This retrospective study provides real-world evidence underscoring that anti-EGFR re-exposure strategies might benefit patients independently of the reason for prior discontinuation.