Combining Anti-epidermal Growth Factor Receptor (EGFR) Therapy with Immunotherapy in Metastatic Colorectal Cancer (mCRC)

ABSTRACTIntroduction Monoclonal antibodies binding the EGFR, such as cetuximab and panitumumab, have been extensively used as targeted therapy for the treatment of mCRC. However, in clinical practice, it has been found that these treatment options have some limitations and fail to fully exploit their immunoregulatory activities. Meanwhile, because of the limited effects of current treatments, immunotherapy is being widely studied for patients with mCRC. However, previous immunotherapy trials in mCRC patients have had unsatisfactory outcomes as monotherapy. Thus, combinatorial treatment strategies are being researched.Areas covered The authors retrieved relevant documents of combination therapy for mCRC from PubMed and Medline. This review elaborates on the knowledge of immunomodulatory effects of anti-EGFR therapy alone and in combination with immunotherapy for mCRC.Expert opinion Although current treatment options have improved median overall survival (OS) for advanced disease to 30 months, the prognosis remains challenging for those with metastatic disease. More recently, the combination of anti-EGFR therapy with immunotherapy has been shown activity with complementary mechanisms. Hence, anti-EGFR therapy in combination with immunotherapy may hold the key to improving the therapeutic effect of refractory mCRC.KEYWORDS: Anti-EGFR therapycombination therapyimmune checkpoint inhibitorsimmunomodulationmetastatic colorectal cancer Article highlights Despite significant improvements in colorectal cancer (CRC) treatment, the prognosis of patients with mCRC is still poor, with a median overall survival (OS) of approximately 30 months. Although anti-EGFR therapy and immunotherapy are currently seen as confirmed treatment options for patients with mCRC, both are associated with limited efficacy by fueling primary and acquired resistance. Therefore, there is great interest in developing of combined treatment strategies that can enhance efficacy by overcoming the limitations of targeted and immune-based therapies.Anti-epidermal Growth Factor Receptor (Anti-EGFR) therapy and immunotherapy complement each other, by fully and synergistically stimulating both innate and adaptive immune systems against cancer cells, which provides the rationale for combination therapy.Various combinations have been investigated in clinical studies, including Anti-EGFR mAbs plus ICIs; Anti-EGFR mAbs, ICIs plus chemotherapy; BRAF inhibitors, Anti-EGFR mAbs plus ICIs.Some clinical trials are associated with improved survival and tolerated toxicities in treating patients with mCRC, which indicates that anti-EGFR therapy in combination with immunotherapy may hold the key to improving the therapeutic effect of refractory mCRC.The possibilities of anti-EGFR therapy in combination with immunotherapy should be further explored in the future.Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Author ContributionsFeng Xiong collected data, reviewed the literature and wrote the manuscript. Yu-wen Zhou rechecked the manuscript and assisted in drawing. Ya-Ting Hao, Gui-Xia Wei and Xiao-Rong Chen contributed to the proofreading and revision of the manuscript. Meng Qiu designed and revised the manuscript. All authors contributed to the review and approved the submitted version.Additional informationFundingThis paper was funded by the Sichuan Science and Technology Department Key Research and Development Project (grant no. 2022YFS0209) and 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant no. ZYJC21017).