The role of anti-EGFR rechallenge in metastatic colorectal cancer, from available data to future developments: A systematic review

Ciardiello, Davide; Mauri, Gianluca; Sartore-Bianchi, Andrea; Siena, Salvatore; Zampino, Maria Giulia; Fazio, Nicola; Cervantes, Andres

doi:10.1016/j.ctrv.2024.102683

Cited by 3 publications

(1 citation statement)

References 82 publications

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“… 32 , 33 , 34 , 35 , 36 Future trials using larger next-generation sequencing panels for patient selection will contribute to answer this question. 37 Fourth, because of the single-group design of the CRICKET, CAVE, and CHRONOS trials and the reduced number of patients included in the control group of the VELO study, no direct comparison with other therapeutic options could be performed. Fifth, we were not able to evaluate the impact of the burden of hepatic disease (number and dimension of liver metastases) on treatment efficacy.…”

Section: Discussionmentioning

confidence: 99%

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Ciardiello,

Martinelli,

Troiani

et al. 2024

JAMA Netw Open

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ImportanceThe available evidence regarding anti–epidermal growth factor receptor (EGFR) inhibitor rechallenge in patients with refractory circulating tumor DNA (ctDNA) RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) is derived from small retrospective and prospective studies.ObjectiveTo evaluate the efficacy of anti-EGFR rechallenge in patients with refractory ctDNA RAS/BRAF wt mCRC.Design, Setting, and ParticipantsThis nonrandomized controlled trial used a pooled analysis of individual patient data from patients with RAS/BRAF wt ctDNA mCRC enrolled in 4 Italian trials (CAVE, VELO, CRICKET, and CHRONOS) and treated with anti-EGFR rechallenge between 2015 and 2022 (median [IQR] follow-up, 28.1 [25.8-35.0] months).InterventionPatients received anti-EGFR rechallenge therapy, including cetuximab plus avelumab, trifluridine-tipiracil plus panitumumab, irinotecan plus cetuximab, or panitumumab monotherapy.Main Outcomes and MeasuresOverall survival (OS), progression-free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were calculated. Exploratory subgroup analysis evaluating several clinical variables was performed. Safety was reported.ResultsOverall, 114 patients with RAS/BRAF wt ctDNA mCRC (median [IQR] age, 61 [29-88] years; 66 men [57.9%]) who received anti-EGFR rechallenge as experimental therapy (48 received cetuximab plus avelumab, 26 received trifluridine-tipiracil plus panitumumab, 13 received irinotecan plus cetuximab, and 27 received panitumumab monotherapy) were included in the current analysis. Eighty-three patients (72.8%) had received 2 previous lines of therapy, and 31 patients (27.2%) had received 3 or more previous lines of therapy. The ORR was 17.5% (20 patients), and the DCR was 72.3% (82 patients). The median PFS was 4.0 months (95% CI, 3.2-4.7 months), and the median OS was 13.1 months (95% CI, 9.5-16.7 months). The subgroup of patients without liver involvement had better clinical outcomes. The median PFS was 5.7 months (95% CI, 4.8-6.7 months) in patients without liver metastasis compared with 3.6 months (95% CI, 3.3-3.9 months) in patients with liver metastasis (hazard ratio, 0.56; 95% CI, 0.37-0.83; P = .004). The median OS was 17.7 months (95% CI, 13-22.4 months) in patients without liver metastasis compared with 11.5 months (95% CI, 9.3-13.9 months) in patients with liver metastasis (hazard ratio, 0.63; 95% CI, 0.41-0.97; P = .04). Treatments showed manageable toxic effects.Conclusions and RelevanceThese findings suggest that anti-EGFR rechallenge therapy has promising antitumor activity in patients with refractory ctDNA RAS/BRAF wt mCRC. Within the limitation of a subgroup analysis, the absence of liver metastases was associated with significant improved survival.Trial RegistrationClinicalTrials.gov Identifiers: NCT02296203; NCT04561336; NCT03227926; NCT05468892

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Section: Discussionmentioning

confidence: 99%

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Ciardiello,

Martinelli,

Troiani

et al. 2024

JAMA Netw Open

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Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial

Martinelli,

Ciardiello,

Martini

et al. 2024

Clin Drug Investig

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Monoclonal Antibody Therapies in Cancer Immunotherapy

Thanawiroon,

Yingngam

2024

Advances in Medical Diagnosis, Treatment, and Care

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Monoclonal antibodies (mAbs) can significantly improve patient outcomes in cancer treatment while reducing related side effects, offering a targeted therapy alternative to traditional treatment regimens. This chapter describes the development, mechanisms, and applications of mAb therapies as critical components of cancer immunotherapy. The chapter covers the history and progression of the use of mAbs in therapy, their multiple mechanisms—such as immune checkpoint inhibitors, the acumen for cancer antigens and antibody—drug conjugates—and the newest developments in this area. Moreover, this chapter reviews relevant case studies and trial data to compare the impact of these agents on various malignancies. This chapter concludes with a summary of the current challenges—developed resistance, on the one hand—and toxic side effects, e.g., cytokine release syndrome and neurotoxicity, on the other—and prospective avenues of the field.

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The role of anti-EGFR rechallenge in metastatic colorectal cancer, from available data to future developments: A systematic review

Cited by 3 publications

References 82 publications

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Anti-EGFR Rechallenge in Patients With Refractory ctDNA RAS/BRAF wt Metastatic Colorectal Cancer

Radiomic Parameters for the Evaluation of Response to Treatment in Metastatic Colorectal Cancer Patients with Liver Metastasis: Findings from the CAVE-GOIM mCRC Phase 2 Trial

Monoclonal Antibody Therapies in Cancer Immunotherapy

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