Comparison Of Cetuximab Research Articles

Antiproliferative Effects of EGFR inhibitor Cetuximab and PARP Inhibitor Combination on Non-Small Cell Lung Cancer Cell Line A549 and Cervical Cancer Cell Line HeLa.

In this study, the efficacy of Cetuximab and Parp inhibitor (Parp 1 inhibitor) used in targeted therapies, alone or in combination, on non-small cell lung cancer cell line A549 and cervical cancer cell line HeLa cells were evaluated. For this purpose different cell kinetic parameters were used. Cell viability, mitotic index, BrdU labelling index and apoptotic index were evaluated in experiments. In single applications Cetuximab at concentrations ranging from 1 mg/ml to 10 mg/ml and Parp inhibitor at concentrations 5 µM -7 µM - 10 µM were applied. IC50 concentration of Cetuximab for A549 was 1 mg/ml, the IC50 concentration of Cetuximab for HeLa was 2 mg/ml, the IC50 concentration of Parp inhibitor for A549 was 5 µM, and the IC50 concentration of Parp inhibitor for HeLa was 7 µM. In both single and combinations, there was a significant decrease in cell viability, mitotic index, BrdU labelling index and there was a significant increase in apoptotic index. A comparison of cetuximab, PARPi and combination applications showed the superiority of combined applications over single applications in all cell kinetic parameters used.

Targeting metastatic colorectal cancer - present and emerging treatment options.

Metastatic colorectal cancer is a significant cause of morbidity and mortality in the US and around the world. While several novel cytotoxic and biologic therapies have been developed and proven efficacious in the past two decades, their optimal use in terms of patient selection, drug combinations, and regimen sequences has yet to be defined. Recent investigations regarding anti-epidermal growth factor receptor therapies include the comparison of single-agent panitumumab and cetuximab, the benefit of adding cetuximab to chemotherapy in the conversion therapy setting, the comparison of cetuximab and bevacizumab when added to first-line chemotherapy, and predictive biomarkers beyond KRAS exon 2 (codons 12 and 13) mutations. With respect to anti-vascular endothelial growth factor therapies, new data on continuing bevacizumab beyond disease progression on a bevacizumab-containing chemotherapy regimen, the addition of bevacizumab to triplet chemotherapy in the first-line setting, maintenance therapy with bevacizumab plus either capecitabine or erlotinib, the addition of aflibercept to chemotherapy, and regorafenib as monotherapy have emerged. Recent scientific and technologic advances in the field of metastatic colorectal cancer promise to elucidate the biological underpinnings of this disease and its therapies for the goal of improving personalized treatments for patients with metastatic colorectal cancer.

P-0204 - Comparison of Cetuximab and Bevacizumab as First-Line Treatment in KRAS Wild Type Advanced Colorectal Cancer Patients: A Retrospective Analysis

P-0204 - Comparison of Cetuximab and Bevacizumab as First-Line Treatment in KRAS Wild Type Advanced Colorectal Cancer Patients: A Retrospective Analysis

Comparison of cetuximab (Cmab) with panitumumab (Pmab) monotherapy in salvage line against KRAS wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.

663 Background: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) such as Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Monotherapy with Cmab or Pmab demonstrated the effectiveness in salvage-line, and the direct comparison was reported in ESMO 2013 (ASPECCT trial). Methods: Data of 31 pts with mCRC treated by monotherapy with Cmab (HGCSG0901) and 51 pts by monotherapy with Pmab (HGCSG1002) registered from 27 institutions in Japan. Comparison of Cmab with Pmab was retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab vs. Pmab); male/female 20/11 vs. 27/24, median age (range) 65(44-76) vs. 64(44-81), PS 0-1/2-3 21/10 vs. 46/5, number of metastatic organs 1-2/3- 22/9 vs. 25/16. Skin toxicity was common adverse events and was generally similar in two groups. MST was 8.4 months in the Cmab and 8.1 months in the Pmab (p = 0.32). PFS was 3.8 months in the Cmab, as compared with 3.1 months in the Pmab (p = 0.60); the corresponding response rate was 19.4% and 13.7% (p = 0.54). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.939, 95% CI 0.783-1.128, p = 0.503), nor PFS (HR 0.972, 95% CI 0.823-1.148, p = 0.735). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab monotherapy in the salvage-line treatment of pts with mCRC.

Targeted therapy in head/neck and gastric cancers

The epidermal growth factor receptor (EGFR/HER1) is a member of the erbB family of receptor tyrosine kinase proteins, which also includes HER2, HER3, and HER4. EGFR is almost universally expressed in squamous cell carcinoma of head and neck (SCCHN), and high levels of expression have been correlated with a poor clinical prognosis [1]. Cetuximab, an IgG1 monoclonal antibody against EGFR, has demonstrated improved survival and disease control when used in combination with radiation therapy for the treatment of locally advanced SCCHN, and in combination with platinum-based chemotherapy in recurrent or metastatic SCCHN [2-4]. Additionally, single-agent cetuximab is active and provides good disease control rate and duration in platinum-refractory SCCHN [5]. Comparison of cetuximab versus cisplatin concurrently with radiotherapy is under investigation in patients with human papillomavirus-associated oropharyngeal cancer, who have better prognosis and may benefit from less toxic treatment [6]. Overexpression of HER2 in gastric cancer results in aggressive clinical course and poor prognosis [7]. Trastuzumab, a monoclonal antibody against HER2, exhibits antitumor activity in HER2 overexpressed gastric cancer cells, and enhances effects of chemotherapy in gastric cancer xenograft overexpressing HER2 [8]. The ToGA study screened about 3,800 patients with advanced gastric cancer from 24 countries, and HER2 overexpression was detected in 22% [9]. Higher rates of HER2 overexpression occurred in intestinal and proximal or gastroesophageal junction cancers than in diffuse or distal gastric cancers. In TOGA study, 584 patients with HER2 overexpression were randomized to receive fluoropyrimidine and cisplatin treatment with or without trastuzumab. Patients who received trastuzumab plus chemotherapy achieved longer overall survival (13.8 months vs. 11.1 months, P= 0.0046), longer progression-free survival (6.7 months vs. 5.5 months, P=0.0002), and higher response rates (47% vs. 35%, P=0.0017) than those who received chemotherapy alone. Complete response was noted in 5.4% of patients receiving trastuzumab plus chemotherapy vs. 2.4% in chemotherapy alone. There were no significant differences in the toxicities between these two groups. This study has established a new paradigm using trastuzumab in combination with chemotherapy in patients with advanced gastric cancer overexpressing HER2. Neoadjuvant treatment is a standard of care for locally advanced esophageal and gastric cancer. We have previously reported a case of pathological complete response after neoadjuvant chemotherapy with trastuzumab-containing regimen in HER2-overexpressing gastric cancer [10]. Incorporating trastuzumab as a part of neoadjuvant therapy in esophageal and gastric adenocarcinoma overexpressing HER2 is currently under active investigation. Radiation Therapy Oncology Group is conducting a phase III neoadjuvant study in patients with HER2-overexpressing esophageal adenocarcinoma to determine if trastuzumab increases disease-free survival when added to chemoradiotherapy [11]. Other studies conducted in Europe are adding trastuzumab to oxaliplatin-based regimen as perioperative chemotherapy for HER2-overexpressing esophagogastric or gastric adenocarcinoma, and looking for improvement of pathological complete response and disease-free survival [12,13]. Pertuzumab is a monoclonal antibody interfering with HER2 dimerization with other HER receptors such as EGFR, HER3 and HER4. Pertuzumab and trastuzumab bind to HER2 at different sites, and combination of both antibodies leads to stronger inhibition of erbB signaling and greater therapeutic efficacy when combined with docetaxel in breast cancer [14]. Combination of pertuzumab and trastuzumab with platinum-based chemotherapy is currently studied in HER2-overexpressing gastric cancer [15].