Rechallenge with anti-EGFR therapy to extend the continuum of care in patients with metastatic colorectal cancer

Abstract

In patients with RAS wild-type metastatic colorectal cancer (mCRC), an anti-epidermal growth factor receptor (EGFR) monoclonal antibody plus chemotherapy is a standard option for treatment in the first-line setting. Patients who progress while on treatment with anti-EGFR-based therapy can be resistant to further anti-EGFR treatment, but evidence suggests that the anti-EGFR-resistant clones decay, thereby opening the potential for rechallenge or reintroduction in later lines of treatment. Results from recent clinical studies have shown that some patients with mCRC who are rechallenged with anti-EGFR monoclonal antibodies exhibit durable responses. While other therapies have demonstrated improved overall survival in chemorefractory mCRC over the past decade, rechallenge with anti-EGFR monoclonal antibodies in later lines of treatment represents a new option that deserves further investigation in clinical trials. In this review, we summarize the molecular rationale for rechallenge or reintroduction in patients with mCRC who have progressed on earlier-line anti-EGFR treatment and examine the current evidence for using liquid biopsy as a method for selecting rechallenge as a therapeutic option. We also provide an overview of published trials and trials in progress in this field, and outline the potential role of rechallenge in the current clinical setting.

Real-World Evidence of FOLFIRI Combined with Anti-Angiogenesis Inhibitors or Anti-EGFR Antibodies for Patients with Early Recurrence Colorectal Cancer After Adjuvant FOLFOX/CAPOX Therapy: A Japanese Claims Database Study

“…All patient characteristics and hospital characteristics were analyzed at baseline. Anti-EGFR rechallenge, defined as re-introduction of anti-EGFR antibodies in patients who were initially responsive to 2L FOLFIRI + anti-EGFR antibodies, but developed progressive disease, and then switched to a non-anti-EGFR antibody regimen until disease progression [ 18 ], was also evaluated.…”

The ideal reporting of RAS testing in colorectal adenocarcinoma: a pathologists’ perspective

“…Other important applications of liquid biopsy regarding detection of ctDNA in the CRC setting are: (i) analysis of minimal residual disease (MRD) as a prognostic factor and for adjuvant therapy selection 68 , 72 , (ii) identification of RAS and BRAF mutations in the absence of an adequate tissue biopsy in the metastatic setting, and (iii) evaluation of the prognostic significance of cfDNA in early-stage disease 71 , 73 . Technical administration of liquid biopsy samples requires comprehensive, ultra-deep technologies, like NGS platforms or digital PCR (dPCR) systems 74 enabling to detect cancer-related molecular alterations from scant samples. In particular, NGS provides a fast high-throughput, and cost-effective alternative to traditional Sanger sequencing to accurately identify alterations in multiple genes of interest and to provide clinically-useful information.…”

The choice of treatment for chemorefractory colon cancer

“…Факторами, определяющими эффективность повторного применения анти-EGFR, были время от предыдущего их применения более 6-10 мес., исчезновение мутированного клона RAS в крови и эффективность анти-EGFR в первой линии (объективный ответ или стабилизация свыше 6 мес.) [22].…”