Perioperative Triplet Chemotherapy and Cetuximab in Patients With RAS Wild Type High Recurrence Risk or Borderline Resectable Colorectal Cancer Liver Metastases

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 .

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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).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3553 ◽

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.

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Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Clinical Colorectal Cancer ◽

10.1016/j.clcc.2018.11.004 ◽

2019 ◽

Vol 18 (1) ◽

pp. 34-43.e6 ◽

Cited By ~ 2

Author(s):

Filippo Pietrantonio ◽

Christian Cotsoglou ◽

Giovanni Fucà ◽

Salvatore Lo Vullo ◽

Federico Nichetti ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Colorectal Cancer Liver Metastases ◽

Triplet Chemotherapy

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

Gastroenterology Research and Practice ◽

10.1155/2017/8464905 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 5

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.

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