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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In a similar manner to cetuximab, panitumumab works by binding to the extracellular domain of the EGFR receptor thus preventing its activation. This results in halting the cascade of intracellular signals dependent on this receptor. However, although both agents target EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotype and are thought to have slightly different mechanisms of action. In particular, it is thought that antibodies of the IgG1 isotype may activate the complement pathway and mediate ADCC more effectively.
Targeted Therapies
Published in Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke, Radiotherapy and Clinical Radiobiology of Head and Neck Cancer, 2018
Loredana G. Marcu, Iuliana Toma-Dasu, Alexandru Dasu, Claes Mercke
No improvement in clinical outcome with panitumumab was found by the Canadian Cancer Trials Group study HN.6, which randomised patients to receive either standard cisplatin-based chemoradiotherapy or accelerated radiotherapy with panitumumab in locoregionally advanced HNC (Siu et al. 2016). The 2-year, progression-free survival in the anti-EGFR arm was 76% compared with 73% in the cisplatin-radiotherapy arm. Toxicity was also higher in the panitumumab group (92% vs 88%).
Epidermal Growth Factor Receptor Inhibition in Non–Small Cell Lung Cancer
Published in Kishan J. Pandya, Julie R. Brahmer, Manuel Hidalgo, Lung Cancer, 2016
Antonio Jimeno, Manuel Hidalgo
Panitumumab (ABX-EGF, Amgen, Thousand Oaks, California, USA) is a high-affinity, fully human MAb that binds the EGFR in its extracellular domain; blocks the binding of both EGF and TGF-α to various EGFR-expressing human carcinoma-cell lines; and inhibits EGFR tyrosine phosphorylation and cell proliferation (72). Full humanization prevents the development of antibodies against murine epitopes, a potential limitation of MAbs that could result in decreased efficacy. ABX-EGF has evidenced preclinical activity in vitro and in vivo, as single agent and in combination with cytotoxic agents in a wide range of human cancer-cell lines, including pancreatic, prostate, breast, head and neck, and renal human-cell lines (73). Based on these preclinical studies, a biomathematical model was developed to predict antitumor efficacy in patients, and maximum antitumor activity was calculated for maintenance doses between 1 and 3 mg/kg weekly. Initial clinical trials of ABX-EGF in heavily pretreated patients have reported encouraging results. A phase I trial was conducted with a weekly schedule with doses ranging from 0.01 to 2.5 mg/kg weekly for four consecutive weeks and every other week thereafter. In this study, treatment with ABX-EGF was well tolerated and no dose-limiting toxicities were reported (74). Biologic activity, evidenced by reversible acneiform skin rash, was observed at the 1.0 mg/kg dose level. A randomized phase II study is currently evaluating the activity of carboplatin/paclitaxel with or without the addition of panitumumab in patients with chemotherapy-naive advanced NSCLC.
Evaluation of physicochemical and functional similarity of a new CHO derived anti-EGFR antibody P-mAb to its reference medicinal product
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2022
Jitender Nandal, Kanti N. Mihooliya, Himanshu Verma, Nidhi Kalidas, Fnu Ashish, Ravi P. N. Mishra, Debendra K. Sahoo
Biologics such as mAbs are highly complex in terms of molecular structure and its structural elements are critical for function of this drug. In the recent years, though the changes in regulation led to the development of pathways for approval of biosimilars (including mAbs) consequently resulting in increased manufacturing and market approval, it has also expended the requirements of non-clinical characterisation data, both physicochemical and biological, showing the similarity of the proposed protein drug with the originator/RMP. The mechanism of action of panitumumab has previously been described in different studies [17,34]. Binding of EGF or TGF-α to EGFR triggers a cascade of cellular biochemical events including EGFR autophosphorylation and internalisation, which culminates in cell proliferation. Blocking the interaction of ligand to EGFR could result in the arrest of tumour growth [35]. As per the reports on originator molecules panitumumab binds selectively to the EGFR and prevents binding of activating agents (EGF and TGF-α). Panitumumab was found to be more active in cells expressing ≥15,000 EGFR per cell [36].
Advances in the pharmacotherapeutic management of esophageal squamous cell carcinoma
Published in Expert Opinion on Pharmacotherapy, 2021
Chengwei Peng, Deirdre J. Cohen
Similar to cetuximab, panitumumab has also been tested in ESCC. In the phase III POWER trial in advanced ESCC, panitumumab was evaluated in combination with cisplatin and 5-FU [52]. Patients were not selected based on EGFR status. The study was stopped early due to interim analysis that showed futility for improved mOS and an increased mortality rate in the panitumumab arm. On final analysis, overall survival was 10.2 versus 9.4 months for cisplatin and 5-FU without panitumumab vs with panitumumab, respectively (p = 0.43). Toxicity was increased in the panitumumab group with 70.8% of those in the panitumumab group experiencing serious adverse event versus 51.4% in the chemotherapy only group (p = 0.0248). The majority of grade 3–4 adverse events were neutropenia (37.1% in panitumumab group vs 33.3% in control group) and anemia (35.7% in panitumumab group vs 33.3% in control group).
Cost-minimization analysis of biweekly dosing of cetuximab and FOLFIRI compared with panitumumab and FOLFOX for first-line treatment of patients with KRAS wild-type metastatic colorectal cancer in the United States
Published in Journal of Medical Economics, 2021
Wambui Grace Gathirua-Mwangi, Harsheen Sethi, Manuel Geroy Afable, Devarshi Bhattacharyya, Taha Khan
Colorectal cancer (CRC) is the second most common cause of cancer-related mortality in the United States (US)1 accounting for approximately 11% of all cancer deaths2. Treatment options for metastatic CRC (mCRC) have expanded over the years and include several targeted therapies given as monotherapy or in combination with chemotherapy agents3,4. Cetuximab and panitumumab are targeted therapies that bind to the human epidermal growth factor receptor (EGFR). Both drugs are approved by the US Food and Drug Administration (FDA) for the treatment of patients with Kirsten’s rat sarcoma (KRAS) wild type (WT) mCRC5. Cetuximab is indicated in combination with folinic acid (leucovorin), fluorouracil (FU), and irinotecan (FOLFIRI) as first-line treatment for KRAS WT mCRC6. Cetuximab is approved for both weekly (400 mg/m2 followed by weekly 250 mg/m2) and biweekly (500 mg/m2) dosing7,8. Panitumumab is approved for biweekly dosing at 6 mg/kg and indicated as first-line therapy in combination with folinic acid, FU, and oxaliplatin (FOLFOX)9.