scholarly journals Chemotherapy Plus Cetuximab versus Chemotherapy Alone for Patients with KRAS Wild Type Unresectable Liver-Confined Metastases Colorectal Cancer: An Updated Meta-Analysis of RCTs

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
W. Lv ◽  
G. Q. Zhang ◽  
A. Jiao ◽  
B. C. Zhao ◽  
Y. Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
R0 Resection ◽  
Cochrane Central Register ◽  
Wild Type ◽  
Resection Rate ◽  
Colorectal Cancer Liver Metastases ◽  
Number Of Patients

Purpose. Our study analyses clinical trials and evaluates the efficacy of adding cetuximab in systematic chemotherapy for unresectable colorectal cancer liver-confined metastases patients. Materials and Methods. Search EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials for RCTs comparing chemotherapy plus cetuximab with chemotherapy alone for KRAS wild type patients with colorectal cancer liver metastases (CRLMs). We calculated the relative risks (RRs) with 95% confidence interval and performed meta-analysis of hazard ratios (HRs) for the R0 resection rate, the overall response rate (ORR), the progression-free survival (PFS) and overall survival (OS). Results. 1173 articles were retrieved and 4 RCTs were available for our study. The four studies involved 504 KRAS wild type patients with CRLMs. The addition of cetuximab significantly improved all the 4 outcomes: the R0 resection rate (RR 2.03, p=0.004), the ORR (RR 1.76, p<0.00001), PFS (HR 0.63, p<0.0001), and also OS (HR 0.74, p=0.04); the last outcome is quite different from the conclusion published before. Conclusions. Although the number of patients analysed was limited, we found that the addition of cetuximab significantly improves the outcomes in KRAS wild type patients with unresectable colorectal cancer liver-confined metastases. Cetuximab combined with systematic chemotherapy perhaps suggests a promising choice for KRAS wild type patients with unresectable liver metastases.

LM02-trial perioperative treatment with panitumumab and FOLFIRI in patients with wild-type RAS, potentially resectable colorectal cancer liver metastases.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16046-e16046
Author(s):  
Gudrun Piringer ◽  
Thomas Gruenberger ◽  
Irene Kuehrer ◽  
Dietmar Oefner ◽  
Klaus Kaczirek ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adverse Events ◽  
Liver Metastases ◽  
Objective Response ◽  
Progression Free Survival ◽  
Preoperative Therapy ◽  
Wild Type ◽  
Colorectal Cancer Liver Metastases ◽  
Common Grade ◽  
Grade 3

e16046 Background: Nearly half of patients with colorectal cancer develop liver metastases and only 20% are initially resectable. Surgical resection of liver metastases results in five-year survival rates of 24-48%. Perioperative FOLFOX therapy increases progression free survival. In advanced disease the addition of targeting therapies to chemotherapy results in an overall survival advantage. In this study the efficacy and safety of perioperative panitumumab and FOLFIRI therapy were investigated. Methods: Patients with previously untreated, wild-type RAS, potentially resectable colorectal cancer liver metastases were included. Chemotherapy consisted of irinotecan 180mg/m2 intravenously over 120 minutes and fluorouracil bolus 400mg/m2 intravenously, followed by a 46 h infusion of fluorouracil 2400mg/m2 repeated every 2 weeks. Panitumumab was given as an intravenous dose of 6mg/kg every 2 weeks. Preoperative 4 cycles and postoperative 8 cycles were administered. Primary objectives were the evaluation of efficacy and safety. Results: We enrolled 36 patients in 7 centers in Austria. ITT-analyses included 35 patients. There were 28 men and 7 women, the median age was 66 years. 91.4% completed the planned 4 cycles of preoperative therapy and 82.9% underwent liver resection. R0 resection rate was 82.7%. 20 patients started postoperative chemotherapy and 12 patients completed the planned 8 cycles. Objective response rate after preoperative therapy was 65.7% with one radiological complete remission and 22 partial remissions. In 20% and 5.7% of patients stable disease and progressive disease were documented, respectively. Three patients discontinued preoperative treatment due to adverse events without response evaluation. The most common grade 3 adverse events were diarrhea (n = 4), rash (n = 3) and leukopenia (n = 3) during preoperative therapy. One patient died due to sepsis and one had a pulmonary embolism grade 4. After surgery two patients died due to hepatic failure and one patient had a suture related complication grade 3. Most common grade 3/4 adverse events during postoperative therapy were rash (n = 2), stroke (n = 1) and intestinal obstruction (n = 1). Conclusions: Panitumumab in combination with FOLFIRI as preoperative therapy for operable colorectal liver metastases in RAS wild-type patients results in a radiological objective response rate in 65.7% of patients with a manageable grade 3 diarrhea rate of 14.3%. Progression-free survival and overall survival are still monitored. Clinical trial information: 2012_000265-20 .

FOLFOX plus panitumumab or FOLFOX alone as additive therapy following R0/1 resection of RAS wild-type colorectal cancer liver metastases: The PARLIM trial (AIO KRK 0314).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3553-3553
Author(s):  
Dominik Paul Modest ◽  
Meinolf Karthaus ◽  
Stefan Kasper ◽  
Nicolas Moosmann ◽  
Verena Keitel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Primary Endpoint ◽  
Specific Treatment ◽  
Progression Free Survival ◽  
Favourable Outcome ◽  
Wild Type ◽  
Open Label ◽  
Colorectal Cancer Liver Metastases ◽  
Colorectal Cancer Patients

3553 Background: This trial investigates the addition of panitumumab to chemotherapy with fluorouracil/ folinic acid and oxaliplatin (FOLFOX) in a 2:1 randomized, controlled, open label, phase II trial in RAS wild-type colorectal cancer patients with R0/1-resected liver metastases. Methods: The primary endpoint was progression-free survival (PFS) two years after randomisation. The experimental arm (12 wks of biweekly mFOLFOX6 plus panitumumab followed by 12 wks of panitumumab alone) was considered active if the 2-year-PFS rate was ≥65%. Based on historical data, a 2-year-PFS rate of 50% was estimated in the control arm (12 wks of biweekly FOLFOX). The trial was performed with a power of 80% and an alpha of 0.05. Secondary endpoints included overall survival (OS) and toxicity. The trial is registered with ClinicalTrials.gov, NCT01384994. Results: The full analysis set consists of 70 patients (pts) in the experimental arm and 36 pts in the control arm. The 2-year-PFS rate was 34.3% with FOLFOX plus panitumumab and failed to meet the primary endpoint. The 2-year-PFS rate in the control arm was 25%. In the experimental arm, a more favourable outcome was observed with regard to PFS (HR: 0.72, 95%CI 0.45-1.17; P = 0.18) and OS (HR: 0.76 (95% CI 0.34-1.71, P = 0.51) which did, however, not reach the level of significance. Updated data including toxicity and subgroup analyses might be presented at the meeting Conclusions: The PARLIM trial clearly failed to demonstrate a PFS rate of 65% after resection of colorectal liver metastases 2 years after randomisation, potentially indicating that the generally high frequency of recurrence and the choice of primary endpoint did not correspond in this study population. However, a trend for improved PFS and OS by the addition of panitumumab to 12 wks of FOLFOX followed by 12 wks panitumumab maintenance therapy may support future trials with ant-EGFR antibodies in this specific treatment setting. Clinical trial information: NCT01384994.

A prospective phase II study of neoadjuvant FOLFOX6 plus cetuximab in patients with colorectal cancer and unresectable liver metastasis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14072-e14072
Author(s):  
Jun Ho Ji ◽  
Young Suk Park ◽  
Jeeyun Lee ◽  
Tae Won Kim ◽  
Yong Sang Hong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Liver Metastases ◽  
Disease Progression ◽  
Hepatic Metastases ◽  
Progression Free Survival ◽  
Response Rates ◽  
R0 Resection ◽  
Resection Rate ◽  
Curative Intent

e14072 Background: Colorectal cancer(CRC) with liver-only metastasis is considered potentially curable when liver metastases are completely resectable, while nonresectable liver metastases(NLM) are still incurable. In the latter cases, neoadjuvant chemotherapy could render curability by achieving resectability. We assessed efficacy of neoadjuvant cetuximab combined with FOLFOX6 in colorectal patients with NLM. Methods: Between July 2008 and Dec 2009, 73 patients were enrolled from 11 centers in Korea. Newly diagnosed K-RAS wild type CRC patients with NLM were treated with FOLFOX6 plus cetuximab(provided by Merck Serono) every 2 weeks. Response was evaluated every 3 cycles by CT scan according to RECIST 1.0. Chemotherapy was continued until disease progression or maximum of 12 cycles. Liver metastasectomy was performed at physician’s discretion in patients with enough tumor shrinkage, followed by chemotherapy of same regimen to complete total 12 cycles. The primary endpoint was overall R0 resection rate. The secondary endpoints were the response rates, progression-free survival(PFS), overall survival and toxicity. Results: In total, 73 patients were enrolled and analyzed. The median follow up duration was 28.6 months (range 11.5 to 38.1). Among 53 (72.6%) patients who showed response, surgery with curative intent was attempted in 36 (49.3%) patients. With intention-to-treat analysis, R0 resection rate(RR) was 19.2% (14/73), RFA plus R0, R1 and R2 RR were 8.2% (6/73), 8.2% (6/73), 13.7% (10/73), respectively. Despite neoadjuvant chemotherapy, 37 (50.7%) patients had unresectable hepatic metastases, however. RFA was successfully performed in combination with surgery (n=7) or alone (n=1) in 8 patients of them. Chemotherapy was discontinued in 26 patients due to disease progression (n=13), death (n=2), consent withdrawal (n=10), or protocol violation (n=1). The most common grade 3 and 4 toxicity was neutropenia (10.7%). Median PFS was 14.1 months (range 1.3 - 30.8) in patients received R0 resection and RFA + R0 resection. Conclusions: Neoadjuvant chemotherapy with FOLFOX6 plus cetuximab showed high response rates and increase resection rate in CRC patients with NLM.

scholarly journals Yttrium-90 radioembolization for colorectal cancer liver metastases in KRAS wild-type and mutant patients: Clinical and ccfDNA studies

2016 ◽  
Vol 37 (1) ◽  
pp. 57-65 ◽  
Author(s):  
E. Janowski ◽  
O. Timofeeva ◽  
S. Chasovskikh ◽  
M. Goldberg ◽  
A. Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Wild Type ◽  
Colorectal Cancer Liver Metastases ◽  
Yttrium 90

scholarly journals Conversion Chemotherapy With a Modified FLOX Regimen for Borderline or Unresectable Liver Metastases From Colorectal Cancer: An Alternative for Limited-Resources Settings

2019 ◽  
pp. 1-6
Author(s):  
Renata Colombo Bonadio ◽  
Paulo Henrique Amor Divino ◽  
Jorge Santiago Madero Obando ◽  
Karolina Cayres Alvino Lima ◽  
Débora Zachello Recchimuzzi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Median Overall Survival ◽  
Low Cost ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
R0 Resection ◽  
Free Survival ◽  
Unresectable Liver Metastases

PURPOSE Conversion chemotherapy is often used for borderline or unresectable (B/U) liver metastases from colorectal cancer (CRC) with the aim of achieving resectability. Although intensive and costly regimens are often used, the best regimen in this scenario remains unclear. We aimed to evaluate the outcomes of patients with B/U liver metastases from CRC treated with conversion chemotherapy with the modified fluorouracil, leucovorin, and oxaliplatin (mFLOX) regimen followed by metastasectomy. METHODS We performed a single-center retrospective analysis of patients with B/U liver metastases from CRC treated with chemotherapy with the mFLOX regimen followed by surgery. B/U disease was defined as at least one of the following: more than four lesions, involvement of hepatic artery or portal vein, or involvement of biliary structure. RESULTS Fifty-four consecutive patients who met our criteria for B/U liver metastases were evaluated. Thirty-five patients (64%) had more than four liver lesions, 16 (29%) had key vascular structure involvement, and 16 (29%) had biliary involvement. After chemotherapy, all patients had surgery and 42 (77%) had R0 resection. After a median follow-up of 37.2 months, median progression-free survival (PFS) was 16.9 months and median overall survival (OS) was 68.3 months. R1-R2 resections were associated with worse PFS and OS compared with R0 resection (PFS: hazard ratio, 2.65; P = .007; OS: hazard ratio, 2.90; P = .014). CONCLUSION Treatment of B/U liver metastases from CRC with conversion chemotherapy using mFLOX regimen followed by surgical resection was associated with a high R0 resection rate and favorable survival outcomes. On the basis of our results, we consider mFLOX a low-cost option for conversion chemotherapy among other options that have been proposed.

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