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In this updated analysis of the EXPERT-C trial we show that, in magnetic resonance imaging-defined, high-risk, locally advanced rectal cancer, adding cetuximab to a treatment strategy with neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX is not associated with a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) in both KRAS/BRAF wild-type and unselected patients. In a retrospective biomarker analysis, TP53 was not prognostic but emerged as an independent predictive biomarker for cetuximab benefit. After a median follow-up of 65.0 months, TP53 wild-type patients (n = 69) who received cetuximab had a statistically significant better PFS (89.3% vs 65.0% at 5 years; hazard ratio [HR] = 0.23; 95% confidence interval [CI] = 0.07 to 0.78; two-sided P = .02 by Cox regression) and OS (92.7% vs 67.5% at 5 years; HR = 0.16; 95% CI = 0.04 to 0.70; two-sided P = .02 by Cox regression) than TP53 wild-type patients who were treated in the control arm. An interaction between TP53 status and cetuximab effect was found (P < .05) and remained statistically significant after adjusting for statistically significant prognostic factors and KRAS.
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http://dx.doi.org/10.1093/jnci/dju121 | DOI Listing |
Front Oncol
November 2024
Department of Medical Oncology, Catalan Institute of Oncology (ICO), L'Hospitalet de Llobregat, Barcelona, Spain.
Objectives: Anti-PD-(L)1 agents changed the landscape of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) treatment. Previous studies showed improved response rates to salvage chemotherapy (SCT) after progression to anti-PD-(L)1 agents. This study aims to evaluate the outcomes of SCT and to identify predictors of response and survival in patients with R/M HNSCC.
View Article and Find Full Text PDFMol Oncol
December 2024
Department of Medicine III, LMU Klinikum, Comprehensive Cancer Center Munich, Germany.
The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. This study was accompanied by a prospective translational project analyzing cell-free circulating tumor DNA (ctDNA) in plasma to test whether ctDNA analysis may help to guide clinical treatment decision making.
View Article and Find Full Text PDFJ Gastrointest Cancer
December 2024
Medical Oncology Department, BC Cancer Agency, University of British Columbia, Vancouver, Canada.
Background: Metastatic colorectal cancer (mCRC) remains a significant clinical challenge. While anti-EGFR inhibitors have improved survival rates, their long-term efficacy is limited by disease progression, which is often associated with the development of acquired resistance mutations. However, some patients may regain sensitivity to anti-EGFR agents after alternative therapies, suggesting a potential benefit for rechallenge strategies.
View Article and Find Full Text PDFLancet Oncol
December 2024
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Background: Management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC) when cisplatin is contraindicated is controversial. We aimed to assess whether radiotherapy with concurrent and adjuvant durvalumab would improve outcomes compared with radiotherapy with cetuximab.
Methods: NRG-HN004 was designed as an open-label, multicentre, parallel-group, randomised, phase 2/3 trial with safety lead-in conducted at 89 academic and community medical centres in North America.
Appl Health Econ Health Policy
November 2024
Canadian Centre for Applied Research in Cancer Control, BC Cancer, Vancouver, BC, Canada.
Background And Objective: Mutations in KRAS and NRAS are predictive of poor response to cetuximab and panitumumab, two anti-epidermal growth factor receptor (EGFR) monoclonal antibodies used in metastatic colorectal cancer (mCRC). Our objective was to explore the value of using KRAS and NRAS mutation status to inform third-line anti-EGFR therapy for mCRC using the value of heterogeneity (VOH) framework.
Methods: We used administrative data to identify mCRC patients who were potentially eligible for third-line therapy in 2006-2019 in British Columbia (BC), Canada.
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