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)

Dewdney, Alice; Cunningham, David; Tabernero, Josep; Capdevila, Jaume; Glimelius, Bengt; Cervantes, Andrés; Tait, Diana; Brown, Gina; Wotherspoon, Andrew; Castro, David González de; Chua, Yu Jo; Wong, Rachel; Barbáchano, Yolanda; Oates, J.; Chau, Ian

doi:10.1200/jco.2011.39.6036

Cited by 348 publications

(222 citation statements)

References 41 publications

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“…In 169 patients assessed with MRI post NAC only 1% (2 patients) progressed and the overall response rate by intention to treat was 63% [43,47,48]. GCR3 was a randomised phase II study of pre-operative OxCap followed by CRT then surgery vs. CRT then surgery then post-operative OxCap in 108 patients.…”

Section: Rationale For Neoadjuvant Chemotherapy In Rectal Cancermentioning

confidence: 99%

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Gollins

Sebag‐Montefiore

2016

Clinical Oncology

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Improved surgical technique plus selective pre-operative radiotherapy, has decreased rectal cancer pelvic local recurrence (LR) from historically 25%, down to approximately 5-10%. However, this improvement has not reduced distant metastatic relapse, the main cause of death and a key issue in rectal cancer management.The current standard is local pelvic treatment (surgery +/-pre-operative radiotherapy) followed by adjuvant chemotherapy (AC), depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline MRI, downstaging long-course pre-operative chemoradiation (LCPCRT) is generally used. However, for non-CRM threatened disease, varying approaches are currently adopted in the UK, including straight to surgery (STS), short-course pre-operative radiotherapy (SCPRT) and LCPCRT.Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating pre-operative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse.Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy based schedules.

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Section: Rationale For Neoadjuvant Chemotherapy In Rectal Cancermentioning

confidence: 99%

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Gollins

Sebag‐Montefiore

2016

Clinical Oncology

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“…Ninety (60%) of the 149 assessable tumors were K-RAS or BRAF wild-type and in these patients the addition of cetuximab did not improve pCR, the primary end point (9% versus 11%, respectively; p = 1.0, HR 1.22) or PFS (HR 0.65, p = 0.363). However, cetuximab significantly improved response rate (CAPOX versus CAPOX + C: after chemotherapy, 51% versus 71%, respectively; p = 0.038) and OS (HR 0.27, p = .034) [24].…”

Section: Cetuximabmentioning

confidence: 95%

“…Surprisingly, in the randomized phase II EXPERT-C trial evaluating capecitabine and oxaliplatin with or without cetuximab as induction regimen followed by CRT with capecitabine and concomitant radiotherapy (without cetuximab) in patients with high-risk wild-type-KRAS LARC, cetuximab significantly increased the response rate and overall survival, but not pCR (the primary end-point of the trial) [24]. These data are in line with results from other three independent trials where patients with LARC received cetuximab combined with chemoradiation [72,73].…”

Section: Predictive Factorsmentioning

confidence: 99%

“…A large multinational randomized phase II study (the EXPERT-C study) compared neoadjuvant therapy with oxaliplatin, capecitabine, and CRT with or without cetuximab in 164 patients [24]. Patients with magnetic resonance imaging (MRI)-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).…”

Section: Cetuximabmentioning

confidence: 99%

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The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer

Torino

Sarmiento

Gasparini

2013

Critical Reviews in Oncology/Hematology

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“…Innovative techniques such as intensity-modulated (IMRT; [20]) and image-guided (IGRT; [13]) radiotherapy will further permit adverse effects to be minimized. Individual response and toxicity scores [47] may be another promising tool and new concepts for systemic treatment are warranted for patients at risk of distant metastases [6,33,34,46]. Doubtlessly, quality optimization of established procedures, such as high resolution MRI or TME in the mesorectal plane, should promptly be translated into clinical routine.…”

Section: Should the Level Of Evidence Be Neglected?mentioning

confidence: 99%

Rectal cancer

et al. 2013

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When is the local recurrence risk low enough to refrain from the aim to prevent it?Local recurrence (LR) of rectal cancer is a devastating incident for each affected individual [2,21]. Thus, along with the attempt of improving survival, local tumor control has been an essential goal in the management of rectal cancer. Adjuvant radiotherapy (RT) with or without chemotherapy (ChT) reduced local recurrence and became a standard treatment in the 1980s [14], which was later on gradually replaced by preoperative RT (nRT) [9,45] or neoadjuvant radiochemotherapy (nRCT) [3,4,10,34,37]. Further substantial progress in terms of local recurrence reduction was achieved with the advent of quality-assured total mesorectal excision (TME; [15]). The next step was the introduction of magnetic resonance imaging (MRI) as a routine preoperative staging tool [1] facilitating the visualization of the distance between tumor and mesorectal fascia. If this distance is ≥1 mm on MRI, a negative circumferential resection margin (CRM) is assumed, provided that total mesorectal excision surgery is performed adequately. A negative CRM (defined as ≥1 mm on pathological work-up) has consecutively been identified and validated as an important surrogate parameter to predict the individual LR risk [12]. Results of the MERCURY study group (Magnetic Resonance Imaging in Rectal Cancer European Equivalence Study) whose authors propagated and investigated MRI-based treatment for rectal cancer were encouraging [23,43] and promoted similar attempts in the German-speaking community such as the OCUM study (optimized surgery and MRI-based multimodal therapy of rectal cancer). Preliminary results were recently published [22,42] and are commented in this editorial.Altogether, 230 patients with rectal cancer clinically staged as cT2-4, any cN, cM0 were included in this observational study. The anticipated CRM assessed by MRI (mrCRM) was used as a decision tool for selecting patients (n=230) either to undergo primary surgery (n=134) or to receive nRCT (n=96). For the lower third of the rectum (defined as <6 cm from the anal verge, 37%), nRCT was performed in all cT3 and cT4 tumors, irrespective of the anticipated CRM status; tumors of the middle third (i.e., 6 to <12 cm) were treated by nRCT in case of positive mrCRM only. For the upper third (12-16 cm), the decision was left to the discretion of the treating center. Clinically positive lymph nodes did not influence the choice of therapy; in patients with pathologically positive lymph nodes, chemotherapy was offered according to the standard of the respective centers. Postoperative RCT was restricted to patients with an involved CRM (pCRM ≤1 mm) [42].The mrCRM was positive in 74/230 patients, 72 in the nRCT group and 2 of the patients selected for surgery alone. A pathologically positive CRM (pCRM) occurred in 5.7% of all patients (nCRT: 11%, primary surgery: 1.5%). Pathology revealed complete remission (ypT0N0) after nRCT in 15% of patients, a partial remission in 67%. Even in patients whose margins were involv...

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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)

Abstract: Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.

Cited by 348 publications

References 41 publications

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

The contribution of targeted therapy to the neoadjuvant chemoradiation of rectal cancer

Rectal cancer

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