P-118 Cetuximab rechallenge in RAS, BRAF, EGFR-ECD wild type metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies in first line: The CITRIC study

Vivas, C. Santos; Salva, F.; Fernández-Rodríguez, Concepción; Orduña, Vicente Alonso; Losa, F.; Páez, David; Vidal, Joana; Salud, A.; Fernandez, Paula Ribera; Aguilera, M. Safont; Tarazona, Noelia; Hernández-Yagüe, X.; Romero, L. Layos; García‐Carbonero, Rocío; Rivera, F.; Gallego, R. Álvarez; Bellosillo, B.; Montagut, Clara

doi:10.1016/j.annonc.2022.04.208

Cited by 7 publications

(3 citation statements)

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“…In prospective trials such as CHRONOS, CRICKET, and GEMCAD 17-01, patients with RAS/BRAF wild type were granted the opportunity for a therapeutic rechallenge if ctDNA testing revealed an absence of mutations in those genes. Those individuals who received personalised therapy based on their mutational status exhibited response rates ranging from 20 to 30% [39][40][41]. Therefore, monitoring guided by ctDNA facilitates the noninvasive molecular identification of patients within a subset of CRC who may exhibit a favourable response to anti-EGFR therapy.…”

Section: Discussionmentioning

confidence: 99%

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

Zarkavelis,

Amylidi,

Torounidou

et al. 2024

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Section: Discussionmentioning

confidence: 99%

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

Zarkavelis,

Amylidi,

Torounidou

et al. 2024

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“…Liquid biopsy has thus far been used retrospectively to assay ctDNA for mutational status. Current studies ( Table 2 ) using liquid biopsy include the randomized FIRE-4 (AIO KRK-0114) trial (which is comparing cetuximab rechallenge with other treatment regimens in the third line) ( 66 ), the CITRIC trial (a randomized trial comparing cetuximab rechallenge to investigator’s choice in liquid biopsy triple negative RAS , BRAF , EGFR -ECD wt tumors) ( 67 ), the PARERE study (NCT04787341) comparing panitumumab rechallenge followed by regorafenib vs the reverse sequence in patients with RAS and BRAF wt ctDNA ( 68 ) and the PULSE trial (NCT03992456) comparing rechallenge with panitumumab vs regorafenib or trifluridine/tipiracil in refractory RAS wt mCRC ( 69 ). Future studies should include prospective analyses that better characterize the use of liquid biopsy to track and identify resistance.…”

Section: Future Perspectivesmentioning

confidence: 99%

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

et al. 2023

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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.

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“…These clinical results demonstrated that patient selection based on ctDNA can better select appropriate candidates for anti-EGFR mAb rechallenge ( 12 ). In addition, the CITRIC trial is an ongoing study comparing the efficacy of cetuximab + CPT-11 rechallenge in third-line therapy with that of the physicians’ choice of therapy in selected patients with RAS , BRAF , and EGFR -ECD wild-type mCRC, using next-generation sequencing panels ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer

et al. 2023

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BackgroundTreatment with anti-EGFR antibody has been shown to prolong survival in patients with RAS wild-type metastatic colorectal cancer (mCRC). However, even patients who initially respond to anti-EGFR antibody therapy, almost without exception, develop resistance to the therapy and then fail to respond. Secondary mutations in the mitogen-activated protein (MAPK) signaling pathway (mainly in NRAS and BRAF) have been implicated in anti-EGFR resistance. However, the process by which resistant clones develop during therapy has not been elucidated, and considerable intrapatient and interpatient heterogeneity exists. Circulating tumor DNA (ctDNA) testing has recently allowed the noninvasive detection of heterogeneous molecular alterations that underlie the evolution of resistance to anti-EGFR. In this report, we describe our observation of genomic alterations in KRAS and NRAS in a patient with acquired resistance to anti-EGFR antibody drugs by tracking clonal evolution using serial ctDNA anaylsis.Case presentationA 54-year-old woman was initially diagnosed with sigmoid colon cancer with multiple liver metastases. After receiving first-line mFOLFOX + cetuximab, second-line FOLFIRI + ramucirumab, third-line trifluridine/tipiracil + bevacizumab, fourth-line regorafenib, and fifth-line CAPOX + bevacizumab, she was rechallenged with CPT-11 + cetuximab. The best response to anti-EGFR rechallenge therapy was a partial response. RAS in the ctDNA was assessed during treatment. The RAS status changed from wild type to mutant type, back to wild type, and again to mutant type (NRAS/KRAS codon 61) during the course of treatment.ConclusionIn this report, tracking of ctDNA allowed us to describe clonal evolution in a case in which we observed genomic alterations in KRAS and NRAS in a patient who acquired resistance to anti-EGFR antibody drugs during treatment. It is reasonable to consider repeat molecular interrogation during progression in patients with mCRC by using ctDNA analysis, which could help to identify patients who may benefit from a rechallenge strategy.

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P-118 Cetuximab rechallenge in RAS, BRAF, EGFR-ECD wild type metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapies in first line: The CITRIC study

Cited by 7 publications

References 0 publications

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

Exploring RAS mutation incidence and temporal heterogeneity in metastatic colorectal cancer patients – a single-institution experience utilising circulating tumour DNA

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

Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer

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