0000000000014324
AUTHOR
Jacqueline Oates
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer
There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 cases ctDNA…
Panex: A pooled analysis of EXPERT and EXPERT-C, two trials of neoadjuvant chemotherapy (NACT) and chemoradiotherapy (CRT) in high-risk locally advanced rectal cancer (LARC).
3575 Background: After the use of preoperative radiotherapy and TME, survival of LARC has reached a plateau. More effective therapies, predictive/prognostic factors for treatment selection and vali...
FcγRIIa and Fc γ RIIIa Polymorphisms and Cetuximab Benefit in the Microscopic Disease
Abstract Purpose: FcγR polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX ± cetuximab in high-risk, locally advanced rectal cancer. Experimental Design: FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment…
Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients
Summary Analysis of a polymorphism in mature microRNA-608 (rs4919510) in rectal cancer patients enrolled in a randomized phase II clinical trial identified patient subpopulations who might benefit from the use of an intensified neo-adjuvant treatment strategy with Cetuximab.
Multicenter Randomized Phase II Clinical Trial Comparing Neoadjuvant Oxaliplatin, Capecitabine, and Preoperative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision in Patients With High-Risk Rectal Cancer (EXPERT-C)
Purpose To evaluate the addition of cetuximab to neoadjuvant chemotherapy before chemoradiotherapy in high-risk rectal cancer. Patients and Methods Patients with operable magnetic resonance imaging–defined high-risk rectal cancer received four cycles of capecitabine/oxaliplatin (CAPOX) followed by capecitabine chemoradiotherapy, surgery, and adjuvant CAPOX (four cycles) or the same regimen plus weekly cetuximab (CAPOX+C). The primary end point was complete response (CR; pathologic CR or, in patients not undergoing surgery, radiologic CR) in patients with KRAS/BRAF wild-type tumors. Secondary end points were radiologic response (RR), progression-free survival (PFS), overall survival (OS), an…
FCγRIIa and FCγRIIIa polymorphisms (SNPs) and cetuximab (C) benefit in the EXPERT-C trial.
3573 Background: FCγRIIa-H131R and FCγRIIIa-V158F SNPs have been reported to enhance the immune-mediated effects of monoclonal antibodies including cetuximab (C) in metastatic colorectal cancer (CR...
The impact of TP53 mutation on high-risk rectal cancer patients treated within the EXPERT-C trial, a randomized phase II study of neoadjuvant oxaliplatin/capecitabine (CAPOX) and chemoradiation (CRT) with or without cetuximab.
e14088 Background: The EXPERT-C trial randomised 165 patients into neoadjuvant CAPOX and CRT ± cetuximab and demonstrated a significant increase in radiological response (RR) and overall survival (OS) with cetuximab in KRAS/BRAF wild type (WT) rectal cancer (Dewdney et al JCO in press). TP53 mutation has been associated with worse CRT response and survival in rectal cancer and could lead to stimulation of PI3K signalling pathway, thus potential resistance to cetuximab. This analysis evaluates the impact of TP53 mutation in the EXPERT-C trial. Methods: FFPE tissue from biopsy (n=102) and resection specimens (n=99) were analysed for TP53 mutations (exons 5-8) using a multiplex PCR method fol…
KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer.
Abstract There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples of 97 LARC patients who were treated with CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX ± cetuximab in a randomised phase II trial. KRAS mutation in G12D, G12V or G13D was detected in the ctDNA of 43% and 35% of patients with tumours that were mutant and wild-type for these hotspot mutations, respectively, according to standard PCR-based analyses on tissue. The detection rate in the ctDNA of 10 patients with less common mutations was 50%. In 26 ca…
Short- and Long-Term Quality of Life and Bowel Function in Patients With MRI-Defined, High-Risk, Locally Advanced Rectal Cancer Treated With an Intensified Neoadjuvant Strategy in the Randomized Phase 2 EXPERT-C Trial
Objective Intensified preoperative treatments have been increasingly investigated in locally advanced rectal cancer (LARC), but limited data are available for the impact of these regimens on quality of life (QoL) and bowel function (BF). We assessed these outcome measures in EXPERT-C, a randomized phase 2 trial of neoadjuvant capecitabine combined with oxaliplatin (CAPOX), followed by chemoradiation therapy (CRT), total mesorectal excision, and adjuvant CAPOX with or without cetuximab in magnetic resonance imaging-defined, high-risk LARC. Methods and Materials QoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaires. Bowel inc…