science

Panitumumab

Panitumumab is a science topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Panitumumab rather than just read about it. In short: Panitumumab, sold under the brand name Vectibix, is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as EGF receptor, EGFR, ErbB-1 and HER1 in humans). Panitumumab is manufactured by Amgen and was originally developed by Abgenix Inc.

Key takeaways

Panitumumab belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Panitumumab to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Panitumumab from memory before moving on to harder problems.

Reference excerpt

Panitumumab, sold under the brand name Vectibix, is a fully human monoclonal antibody specific to the epidermal growth factor receptor (also known as EGF receptor, EGFR, ErbB-1 and HER1 in humans). Panitumumab is manufactured by Amgen and was originally developed by Abgenix Inc. In 2014, Amgen and Illumina entered into an agreement to develop a companion diagnostic to accompany panitumumab.

Medical uses Panitumumab was approved by the U.S. Food and Drug Administration (FDA) for the first time in September 2006 for "the treatment of EGFR-expressing metastatic colorectal cancer with disease progression" despite prior treatment. Panitumumab was approved by the European Medicines Agency (EMEA) in 2007, and by Health Canada in 2008, for "the treatment of refractory EGFR-expressing metastatic colorectal cancer in patients with non-mutated (wild-type) KRAS". Panitumumab was the first monoclonal antibody to demonstrate the use of KRAS as a predictive biomarker.

Contraindications Panitumumab does not work in patients who have KRAS or NRAS mutations.

Adverse effects Panitumumab has been associated with skin rash, fatigue, nausea, diarrhea, fever, and decreased magnesium levels. Often, skin rash is noted in the sun exposed parts of the body, such as the face or chest. Oral antibiotics may be needed for worsening skin rash, such as one accompanied with blisters and ulcers. Otherwise, topical steroid creams like hydrocortisone may help. Ocular toxicity or keratitis was observed in 16% of patients on panitumumab, usually necessitating the discontinuance of therapy. In clinical trials, 90% of patients had dermatological toxicities and 15% of those were severe. Because of this, panitumumab has a boxed warning cautioning patients. Skin toxicities were typically apparent two weeks after beginning treatment. More severe skin toxicities were associated with improved progression free survival and overall survival. Pulmonary fibrosis and interstitial lung disease were observed in clinical trials.

Pharmacology

Mechanism of action

EGFR is a transmembrane protein. Panitumumab works by binding to the extracellular domain of the EGFR preventing its activation. This results in halting of the cascade of intracellular signals dependent on this receptor.

Pharmacokinetics The pharmacokinetics (PK) of panitumumab shows the so-called target-mediated disposition behavior. However, the pharmacokinetics is approximately linear at clinical doses, and the terminal half-life for a typical male patient of 80 kg and 60 years of age with colorectal cancer is about 9.4 days.

History Panitumumab was generated using Abgenix's XenoMouse platform technology, in which engineered mice were utilized to produce human antibodies. Abgenix partnered with Immunex Corporation to develop the antibody, and Amgen acquired Immunex in 2003. In 2006, Amgen acquired Abgenix as well. In 2013, Amgen formed an agreement with Zhejiang Beta Pharma to form Amgen Beta Pharmaceuticals and market panitumumab in China. Amgen and Takeda have an agreement under which Takeda will develop and commercialise panitumumab in Japan. Panitumumab is licensed to Dr. Reddy's Laboratories in India and GlaxoSmithKline in the UK.

FDA approval Panitumumab was initially approved on September 27, 2006, for EGFR-expressing, metastatic CRC with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimens, based on the results of a study which showed clinical benefit in metastatic colorectal cancer patients. In July 2009, the FDA updated the labels of two anti-EGFR monoclonal antibody drugs (panitumumab and cetuximab) indicated for the treatment of metastatic colorectal cancer to include information about KRAS mutations. This was the result of a study, which demonstrated lack of benefit with Panitumumab in patients who carried NRAS mutations. It is also approved as a first-line agent in combination with FOLFOX.

Research Panitumumab is being studied in numerous phase II and III clinical trials. Phase III clinical trials include treatment of esophageal cancer, urothelial carcinoma, metastatic head and neck cancer, and liver metastasis in colorectal cancer. Early trials showed limited efficacy in patients with melanoma, bladder cancer, prostate cancer, and renal cell carcinoma.

Panitumumab vs. cetuximab Although they both target the EGFR, panitumumab (IgG2) and cetuximab (IgG1) differ in their isotype and they might differ in their mechanism of action. Monoclonal antibodies of the IgG1 isotype may activate the complement pathway and mediate antibody-dependent cellular cytotoxicity (ADCC). It is not clear at this time if one drug is superior to the other. In one of the studies, both these drugs were noted to be similar in activity.

References

Worked examples

Example 1 — a first encounter with Panitumumab

Start with the simplest possible case. Write down what Panitumumab claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Panitumumab before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Panitumumab ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Panitumumab

In research: Panitumumab appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Panitumumab in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Panitumumab is common in secondary-school and first-year university syllabi. It links to neighbouring topics Drugs developed by Amgen, Drugs developed by Takeda Pharmaceutical Company, Monoclonal antibodies for tumors, so understanding it makes those chapters shorter.
In everyday life: Look for Panitumumab outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Panitumumab in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Panitumumab means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Panitumumab out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Panitumumab in simple terms?

Why does Panitumumab matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Panitumumab?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Panitumumab.