Skip to main content

Cetuximab (Monograph)

Brand name: Erbitux
Drug class: Antineoplastic Agents
- Epidermal Growth Factor Receptor (EGFR) Inhibitors
VA class: AN900
Chemical name: Disulfide with human-mouse monoclonal C225 κ-chain anti-(human epidermal growth factor receptor) (human-mouse monoclonal C225 γ1-chain) immunoglobulin G1 dimer
CAS number: 205923-56-4

Medically reviewed by Drugs.com on Apr 18, 2024. Written by ASHP.

Warning

    Infusion-related Effects

  • Severe infusion-related effects (rarely fatal) reported in about 3% of patients.1 6

  • If severe infusion-related effects occur, discontinue cetuximab immediately and permanently.1 (See Infusion-related Effects under Cautions.)

    Cardiopulmonary Arrest

  • Cardiopulmonary arrest and/or sudden death reported in 2% of patients with squamous cell carcinoma of the head and neck receiving cetuximab in combination with radiation therapy.1 (See Cardiopulmonary Arrest under Cautions.)

  • Closely monitor serum electrolytes (including magnesium, potassium, and calcium) during and after cetuximab therapy.1 (See Electrolyte Disorders under Cautions.)

Introduction

Antineoplastic agent; a recombinant chimeric (human-murine) monoclonal antibody that binds to epidermal growth factor receptors (EGFR).1 6 7

Uses for Cetuximab

Colorectal Cancer

Used in combination with irinotecan for the treatment of EGFR-expressing metastatic colorectal cancer that is refractory to irinotecan-based chemotherapy.1 2 3 19 Indication for use in combination with irinotecan is based on objective response rates; currently no data demonstrating clinical benefit (e.g., improvement in disease-related symptoms, increased survival).1

Used as a single agent for the treatment of EGFR-expressing metastatic colorectal cancer in patients with disease that has failed treatment with both irinotecan-based and oxaliplatin-based regimens.1

Also used as a single agent for the treatment of EGFR-expressing metastatic colorectal cancer in patients who are intolerant of irinotecan-based chemotherapy.1 11

Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for EGFR inhibitors (e.g., cetuximab, panitumumab) in patients whose tumors had KRAS (also called K-ras) mutations in codon 12 or 13.1 28 33 34 37 43 ASCO28 and some clinicians31 36 38 39 40 41 42 43 recommend that all patients with metastatic colorectal cancer who are potential candidates for EGFR inhibitor therapy have their tumor tested for KRAS mutations28 31 36 38 39 40 41 42 43 in a Clinical Laboratory Improvement Amendments (CLIA)-accredited laboratory.28 31 If KRAS mutation in codon 12 or 13 is detected, use of cetuximab is not recommended.1 28 31 36

Under investigation for use in combination with chemotherapy regimens (e.g., irinotecan/fluorouracil/leucovorin [FOLFIRI], oxaliplatin/fluorouracil/leucovorin [FOLFOX]) for the first-line† [off-label] treatment of metastatic colorectal cancer.20 21

Head and Neck Cancer

Used in combination with radiation therapy for initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck, particularly in patients who cannot tolerate platinum-based chemotherapy with radiation therapy.1 13 Platinum-based chemotherapy with radiation therapy is current standard of care for treatment of advanced head and neck cancer.13

Used as a single agent for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck when previous platinum-based chemotherapy has failed.1 12

Under investigation for use in combination with other antineoplastic agents (e.g., cisplatin), with or without radiation therapy,† [off-label] for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck.5 14 15 16 17 18

Non-small Cell Lung Cancer (NSCLC)

Use in combination with chemotherapy as first-line therapy for advanced (stage IIIB [with malignant pleural effusion] or IV [metastatic]) NSCLC† [off-label] is not fully established because of equivocal evidence;10024 additional studies needed to validate predictive tumor biomarkers and identify subgroups of patients with previously untreated advanced NSCLC who might derive clinical benefit (e.g., prolonged progression-free survival, prolonged overall survival, improved quality of life) from the addition of cetuximab to chemotherapy.10017 10021 10022 10023

Cetuximab Dosage and Administration

General

Administration

IV Administration

Administer by IV infusion.1 7 Do not administer by rapid IV injection, such as IV push or bolus.1

Solution should be clear and colorless and may contain small amounts of easily visible, white, amorphous particulates.1

Do not shake vials.1

Contains no preservative; discard any unused portion of vial.1

Use infusion pump or syringe pump to administer.1

Administer drug through a low-protein-binding 0.22-µm inline filter.1

Monitor patients for infusion reactions during and for 1 hour following each infusion.1 7 10 If infusion reaction requiring treatment occurs, monitor until event has resolved.1 10

Dilution

Do not dilute solution.1

Rate of Administration

Initial IV dose: Administer over 2 hours.1

Subsequent weekly doses: Administer over 1 hour.1

Infusion rate should not exceed 10 mg/minute.1

Dosage

Adults

Colorectal Cancer
Cetuximab or Cetuximab/Irinotecan for EGFR-Expressing Metastatic Disease
IV

Initial cetuximab dose of 400 mg/m2, followed by 250 mg/m2 once weekly until disease progression or unacceptable toxicity occurs.1 6 7

Head and Neck Cancer
Cetuximab/Radiation Combination Therapy for Locally or Regionally Advanced Disease
IV

Initial dose of 400 mg/m2 administered 1 week prior to initiation of first course of radiation therapy.1 Then, 250 mg/m2 once weekly for duration of radiation therapy (6–7 weeks); a median of 8 doses was administered in clinical studies.1 Cetuximab administration should be completed 1 hour prior to radiation therapy.1

Monotherapy for Recurrent or Metastatic Disease
IV

Initial dose of 400 mg/m2, followed by 250 mg/m2 once weekly until disease progression or unacceptable toxicity occurs.1

Dosage Modification for Toxicity and Contraindications to Continued Therapy
Infusion-related Reactions

If grade 1 or 2 or nonserious grade 3 or 4 infusion-related reaction occurs, reduce infusion rate by 50%.1 6

If serious infusion-related reaction (requiring medical intervention and/or hospitalization) occurs, discontinue therapy immediately and permanently.1

Dermatologic Toxicity

If severe (grade 3 or 4) acneiform rash occurs, temporarily delay therapy; reduce subsequent doses or discontinue therapy depending on patient's response as follows:1

Cetuximab Dosage Modification for Severe Acneiform Rash1

Occurrence of Severe Acneiform Rash

Intervention

Outcome

Cetuximab Dosage

First occurrence

Delay infusion for 1–2 weeks

Improvement

Continue subsequent weekly dose of 250 mg/m2

No improvement

Discontinue cetuximab

Second occurrence

Delay infusion for 1–2 weeks

Improvement

Reduce subsequent weekly dose to 200 mg/m2

No improvement

Discontinue cetuximab

Third occurrence

Delay infusion for 1–2 weeks

Improvement

Reduce subsequent weekly dose to 150 mg/m2

No improvement

Discontinue cetuximab

Fourth occurrence

Discontinue cetuximab
Pulmonary Toxicity

If acute onset or worsening of pulmonary symptoms occurs, interrupt therapy.1 If interstitial lung disease is confirmed, permanently discontinue therapy.1

Special Populations

No special population dosage recommendations at this time.4

Detailed Cetuximab dosage information

Cautions for Cetuximab

Contraindications

Warnings/Precautions

Warnings

Infusion-related Effects

Potential for serious infusion-related effects (e.g., rapid airway obstruction [bronchospasm, stridor, hoarseness], hypotension, shock, loss of consciousness, MI, cardiac arrest).1 (See Infusion-related Effects in Boxed Warning.) Infusion-related effects are severe (grade 3 or 4) in 2–5% of patients; fatal in less than 1 in 1000 patients.1 Approximately 90% of severe reactions occur in association with initial cetuximab infusion despite premedication with antihistamines.1

Monitor for signs of infusion reactions during and for 1 hour following each cetuximab infusion in a setting where resuscitation equipment and agents necessary to treat anaphylaxis are readily available.1 7 10 For patients experiencing infusion reactions requiring treatment, monitor until event has resolved.1 10

If grade 1 or 2 or nonserious grade 3 or 4 infusion-related reaction occurs, reduce infusion rate by 50%.1

If serious infusion-related effects occur, discontinue cetuximab immediately and permanently and initiate appropriate therapy (e.g., epinephrine, corticosteroids, IV antihistamines, bronchodilators, oxygen).1

Cardiopulmonary Arrest

Cardiopulmonary arrest and/or sudden death reported in patients with or without CAD, arrhythmia, and/or CHF receiving cetuximab/radiation combination therapy for treatment of squamous cell carcinoma of the head and neck.1 (See Cardiopulmonary Arrest in Boxed Warning.)

Carefully consider use of cetuximab and radiation therapy for treatment of head and neck cancer in patients with a history of CAD, CHF, or arrhythmias.1 Closely monitor serum electrolytes, including magnesium, potassium, and calcium, during and following cetuximab therapy.1

Serious cardiotoxicity requiring discontinuance of therapy also reported in patients with squamous cell carcinoma of the head and neck receiving cetuximab in combination with cisplatin and radiation therapy (see Use in Combination with Radiation Therapy and Cisplatin under Cautions).1

Pulmonary Effects

Interstitial lung disease, interstitial pneumonitis (fatal in one case), and exacerbation of preexisting fibrotic lung disease reported.1 4 6

If acute onset or exacerbation of pulmonary manifestations occurs, interrupt therapy.1 If interstitial lung disease is confirmed, permanently discontinue therapy.1

Use in Combination with Radiation Therapy and Cisplatin

Safety of combination regimen consisting of cetuximab, radiation therapy, and cisplatin not established.1 Serious cardiotoxicity and death (secondary to pneumonia or unknown cause) reported in patients receiving this combination for treatment of locally advanced squamous cell carcinoma of the head and neck.1

Electrolyte Disorders

Electrolyte abnormalities, including hypomagnesemia, hypocalcemia, and hypokalemia, have occurred.1 Hypomagnesemia reported in 55% of patients; severe (grade 3 or 4) in 6–17% of patients.1 Onset of hypomagnesemia and accompanying electrolyte abnormalities may occur from days to months following initiation of therapy.1 10 Manifestations of hypomagnesemia may include fatigue and hypocalcemia.23

Monitor for hypomagnesemia, hypocalcemia, and hypokalemia during and for ≥8 weeks following completion of therapy.1 Replete electrolytes as necessary; IV replacement therapy indicated in severe cases.1 10 23

Sensitivity Reactions

Dermatologic Effects

Acneiform rash reported in 76–88% of patients; severe in 1–17%.1 Generally appears within first 2 weeks of therapy and may resolve following discontinuance; however, may persist beyond 28 days.1

Skin drying/fissuring,1 paronychial inflammation,1 infectious sequelae (e.g., abscess formation, blepharitis, conjunctivitis, keratitis, cheilitis, cellulitis, Staphylococcus aureus sepsis),1 and hypertrichosis1 24 reported.1 Fatal toxic epidermal necrolysis also reported.27

Monitor for possible dermatologic effects and infectious complications.1 If severe acneiform rash occurs, reduce dosage or discontinue therapy.1 (See Dermatologic Toxicity under Dosage and Administration.)

Limit sun exposure.1 (See Advice to Patients.)

General Precautions

EGFR Expression and Response

In clinical trials for colorectal cancer, testing for evidence of EGFR expression was required.1 However, some authorities state that routine EGFR expression testing is not recommended in patients with colorectal cancer and that patients should not be included or excluded from cetuximab therapy based solely on EGFR test results.31

Because expression of EGFR has been detected in nearly all head and neck cancers, EGFR testing was not required in these clinical trials.1

Therapy Monitoring

Monitor for dermatologic toxicity and infectious sequelae.1

Periodically monitor for hypomagnesemia and accompanying hypocalcemia and hypokalemia during and for ≥8 weeks following completion of therapy.1 10

Immunologic Effects

Nonneutralizing anticetuximab antibodies detected in about 5% of patients.1 Incidence of antibody development not fully established, but there appears to be no effect on safety and efficacy of the drug.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether cetuximab is distributed into milk, but potential exists for distribution of IgG antibodies into milk.1 Discontinue nursing or the drug; if nursing is interrupted, do not resume for at least 60 days following last dose (due to long half-life).1 (See Half-life under Pharmacokinetics.)

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

In patients receiving monotherapy or combination therapy for colorectal cancer, no overall differences in safety and efficacy relative to younger adults.1

Insufficient experience in patients ≥65 years of age with head and neck cancer to determine whether they respond differently than younger adults.1

Common Adverse Effects

Dermatologic effects (e.g., rash, pruritus, nail changes), headache, diarrhea, infection.1

Combination therapy with irinotecan in patients with advanced colorectal cancer: Acneiform rash, asthenia/malaise, diarrhea, nausea.1

Monotherapy in patients with advanced colorectal cancer: Rash/desquamation, fatigue, abdominal pain, pain, dry skin, dyspnea, constipation.1

In combination with radiation therapy in patients with head and neck cancer: Acneiform rash; radiation dermatitis; weight loss; asthenia; nausea; elevated ALT, AST, and alkaline phosphatase.1

Drug Interactions

Specific Drugs and Therapies

Drug or Therapy

Interaction

Comments

Cisplatin

Pharmacokinetic interaction unlikely1 7

Serious cardiotoxicity and death reported with concomitant use of cetuximab, cisplatin, and radiation1

Docetaxel

Pharmacokinetic interaction unlikely1 7

Fluorouracil

Pharmacokinetic interaction unlikely1 7

Irinotecan

Pharmacokinetic interaction unlikely1 7

Radiation therapy

Increased risk of cardiopulmonary arrest, sudden death, and/or adverse dermatologic effects (e.g., acneiform rash)1

Increased risk of late radiation toxicities1

Use concomitantly with caution in patients with history or clinical evidence of CAD, CHF, or arrhythmias1 (see Cardiopulmonary Arrest under Cautions)
Cetuximab drug interactions (more detail)

Cetuximab Pharmacokinetics

Pharmacokinetics similar between patients with squamous cell carcinoma of the head and neck and those with colorectal cancer.1

Elimination

Elimination Route

Systemic clearance believed to be through internalization of cetuximab-EGFR complex on hepatocytes and skin.7

Half-life

112 hours following multiple dosing.1 6

Special Populations

Clearance increases with increasing body surface area.1

Decreased clearance observed in women.1 No effect on safety profile; effect on efficacy not elucidated.1

Stability

Storage

Parenteral

Injection

2–8°C.1 Do not freeze.1

Preparations in infusion containers are chemically and physically stable for up to 8 hours at 20–25°C or up to 12 hours at 2–8°C.1 Discard any unused portion after 8 hours (if stored at 20–25°C) or after 12 hours (if stored at 2–8°C).1

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cetuximab (Recombinant)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

2 mg/mL (100 and 200 mg)

Erbitux

Bristol-Myers Squibb

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 28, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Bristol-Myers Squibb Company. Erbitux (cetuximab) prescribing information. Princeton, NJ: 2010 Sep.

2. Saltz LB, Meropol NJ, Loehrer PJ et al. Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 2004; 22:1201-8. http://www.ncbi.nlm.nih.gov/pubmed/14993230?dopt=AbstractPlus

3. Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004; 351:337-45. http://www.ncbi.nlm.nih.gov/pubmed/15269313?dopt=AbstractPlus

4. Bristol-Myers Squibb, Princeton, NJ: Personal communication.

5. Burtness B, Goldwasser MA, Flood W et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol. 2005; 23:8646-54. http://www.ncbi.nlm.nih.gov/pubmed/16314626?dopt=AbstractPlus

6. Anon. Two new drugs for colon cancer. Med Lett Drugs Ther. 2004; 46:46-7.

7. Reynolds NA, Wagstaff AJ. Cetuximab: in the treatment of metastatic colorectal cancer. Drugs. 2004; 64:109-18. http://www.ncbi.nlm.nih.gov/pubmed/14723561?dopt=AbstractPlus

8. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2004 Sep 16. From FDA web site. http://www.fda.gov/orphan/designat/list.xls

9. Bonner JA, Harari PM, Giralt J et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006; 354:567-78. http://www.ncbi.nlm.nih.gov/pubmed/16467544?dopt=AbstractPlus

10. Rowinsky EK, Smyth AC. Dear healthcare provider letter regarding important drug warning for Erbitux (cetuximab). ImClone Systems and Bristol Myers Squibb; 2005 Sep 13.

11. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41-52. http://www.ncbi.nlm.nih.gov/pubmed/15529105?dopt=AbstractPlus

12. Vermorken JB, Trigo J, Hitt R et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007; 25:2171-7. http://www.ncbi.nlm.nih.gov/pubmed/17538161?dopt=AbstractPlus

13. Posner MR, Wirth LJ. Cetuximab and radiotherapy for head and neck cancer. N Engl J Med. 2006; 354:634-6. http://www.ncbi.nlm.nih.gov/pubmed/16467552?dopt=AbstractPlus

14. Baselga J, Trigo JM, Bourhis J et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005; 23:5568-77. http://www.ncbi.nlm.nih.gov/pubmed/16009950?dopt=AbstractPlus

15. Herbst RS, Arquette M, Shin DM et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol. 2005; 23:5578-87. http://www.ncbi.nlm.nih.gov/pubmed/16009949?dopt=AbstractPlus

16. Vermorken JB, Mesia R, Rivera F et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008; 359:1116-27. http://www.ncbi.nlm.nih.gov/pubmed/18784101?dopt=AbstractPlus

17. Pfister DG, Su YB, Kraus DH et al. Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm. J Clin Oncol. 2006; 24:1072-8. http://www.ncbi.nlm.nih.gov/pubmed/16505426?dopt=AbstractPlus

18. Ang KK, protocol chair. Phase III randomized study of concurrent accelerated fractionated radiotherapy and cisplatin with versus without cetuximab in patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx. Protocol ID: RTOG-0522. Last modified: 8/24/2006. National Cancer Institute: Clinical Trials (database).

19. Saltz L, Rubin M, Hochster H et al. Cetuximab (IMC-C225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR). Proc ASCO. 2001; Abstract No. 7.

20. Venook A, Niedzwiecki D, Hollis D et al. Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX) ± cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. Proc ASCO. 2006; Abstract No. 3509.

21. Venook A, protocol chair. Phase III randomized study of cetuximab and/or bevacizumab in combination with either oxaliplatin, fluorouracil, and leucovorin calcium (FOLFOX) or irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with previously untreated metastatic adenocarcinoma of the colon or rectum. Protocol ID: CALGB-C80405. Last modified: 8/24/2006. National Cancer Institute: Clinical Trials (database).

22. Chung KY, Shia J, Kemeny NE et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005; 23:1803-10. http://www.ncbi.nlm.nih.gov/pubmed/15677699?dopt=AbstractPlus

23. Schrag D, Chung KY, Flombaum C et al. Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst. 2005; 97:1221-4. http://www.ncbi.nlm.nih.gov/pubmed/16106027?dopt=AbstractPlus

24. Montagut C, Grau JJ, Grimalt R et al. Abnormal hair growth in a patient with head and neck cancer treated with the anti-epidermal growth factor receptor monoclonal antibody cetuximab. J Clin Oncol. 2005; 23:5273-5. http://www.ncbi.nlm.nih.gov/pubmed/16051981?dopt=AbstractPlus

25. Jonker DJ, O’Callaghan CJ, Karapetis CS et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007; 357:2040-8. http://www.ncbi.nlm.nih.gov/pubmed/18003960?dopt=AbstractPlus

26. Lièvre A, Bachet JB, Boige V et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008; 26:374-9.

27. Lin WL, Lin WC, Yang JY et al. Fatal toxic epidermal necrolysis associated with cetuximab in a patient with colon cancer. J Clin Oncol. 2008; 26:2779-80. http://www.ncbi.nlm.nih.gov/pubmed/18509187?dopt=AbstractPlus

28. Allegra CJ, Jessup JM, Somerfield MR et al. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009; 27:2091-6. http://www.ncbi.nlm.nih.gov/pubmed/19188670?dopt=AbstractPlus

29. Cunningham D, Humblet Y, Siena S et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004; 351:337-45. http://www.ncbi.nlm.nih.gov/pubmed/15269313?dopt=AbstractPlus

30. Italiano A, Follana P, Caroli FX et al. Cetuximab shows activity in colorectal cancer patients with tumors for which FISH analysis does not detect an increase in EGFR gene copy number. Ann Surg Oncol. 2008; 15:649-54. http://www.ncbi.nlm.nih.gov/pubmed/17987340?dopt=AbstractPlus

31. National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology; colon cancer. Version 2.2009. Accessed from the NCCN website:/professionals/physician_gls/PDF/colon.pdf https://www.nccn.org/professionals/physician_gls/PDF/colon.pdf

32. Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009; 373:1525-31. http://www.ncbi.nlm.nih.gov/pubmed/19410716?dopt=AbstractPlus

33. Van Cutsem E, Lang I, Moiseyenko V et al. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: the CRYSTAL experience. Proceedings of the 44th Annual Meeting of ASCO, Chicago, IL, 2008 May 30–Jun 3. Abstr. No. 2.

34. Bokemeyer C, Bondarenko I, Hartmann JT et al. KRAS status and efficacy of first-line treatment of patients with metastatic colorectal cancer (mCRC) with FOLFOX with or without cetuximab: the OPUS experience. Proceedings of the 44th Annual Meeting of ASCO, Chicago, IL 2008 May 30–Jun 3. Abstr. No. 4000.

35. Chang DZ, Kumar V, Ma Y et al. Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy. J Hematol Oncol. 2009; 2:18. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2686726&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/19386128?dopt=AbstractPlus

36. Normanno N, Tejpar S, Morgillo F et al. Implications for KRAS status and EGFR-targeted therapies in metastatic CRC. Nat Rev Clin Oncol. 2009; 6:519-27. http://www.ncbi.nlm.nih.gov/pubmed/19636327?dopt=AbstractPlus

37. Bristol-Myers Squibb. Erbitux (cetuximab) solution for intravenous infusion prescribing information. Princeton, NJ: 2009 Jul.

38. Freeman DJ, Juan T, Reiner M et al. Association of K-ras mutational status and clinical outcomes in patients with metastatic colorectal cancer receiving panitumumab alone. Clin Colorectal Cancer. 2008; 7:184-90. http://www.ncbi.nlm.nih.gov/pubmed/18621636?dopt=AbstractPlus

39. Santini D, Loupakis F, Vincenzi B et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist. 2008; 13:1270-5. http://www.ncbi.nlm.nih.gov/pubmed/19056857?dopt=AbstractPlus

40. Di Nicolantonio F, Martini M, Molinari F et al. Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26:5705-12. http://www.ncbi.nlm.nih.gov/pubmed/19001320?dopt=AbstractPlus

41. Peeters M, Balfour J, Arnold D. Review article: panitumumab--a fully human anti-EGFR monoclonal antibody for treatment of metastatic colorectal cancer. Aliment Pharmacol Ther. 2008; 28:269-81. http://www.ncbi.nlm.nih.gov/pubmed/19086328?dopt=AbstractPlus

42. Weber J, McCormack PL. Panitumumab in metastatic colorectal cancer with wild-type KRAS. BioDrugs. 2008; 22:403-11. http://www.ncbi.nlm.nih.gov/pubmed/18998757?dopt=AbstractPlus

43. Amado RG, Wolf M, Peeters M et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008; 26:1626-34. http://www.ncbi.nlm.nih.gov/pubmed/18316791?dopt=AbstractPlus

10001. Pirker R, Szczesna A, von Pawel J et al. FLEX: a randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Proceedings of 44th Annual Meeting of ASCO, Chicago, IL, 2008 May 30-June 3. Abstract No. 3.

10002. Lynch T, Patel T, Dreisbach L et al. A randomized multicenter phase III study of cetuximab (Erbitux) in combination with taxane/carboplatin versus taxane/carboplatin alone as first-line treatment for patients with advanced/metastatic non-small cell lung cancer (NSCLC): BMS 099. Presented at the 12th World Congress on lung cancer. 2007 Sept 2-6. Seoul, Korea. Abstract No. B3-03.

10003. ImClone Systems Inc. Erbitux Phase 3 BMS 099 lung cancer study secondary endpoint update: overall survival results announced. New York, NY; 2008 Aug 29. Press release.

10004. Herbst RS, Chansky K, Kelly K et al. A phase II randomized selection trial evaluating concurrent chemotherapy plus cetuximab or chemotherapy followed by cetuximab in patients with advanced non-small cell lung cancer (NSCLC): final report of SWOG 0342. Proceedings of the 43rd Annual Meeting of ASCO, 2007 Chicago, IL, June 1-5. Abstract No. 7545.

10005. Hirsch FR, Herbst RS, Olsen C, et al. Increased EGFR gene copy number detected by fluorescent in situ hybridization predicts outcome in non-small cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol.2008; 26:3351-57. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3368372&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/18612151?dopt=AbstractPlus

10006. Butts CA, Bodkin D, Middleman ELet al. Randomized phase II study of gemcitabine plus cisplatin, with or without cetuximab, as first-line therapy for patients with advanced or metastatic non-small cell lung cancer. J Clin Oncol. 2007; 25:5777-84. http://www.ncbi.nlm.nih.gov/pubmed/18089875?dopt=AbstractPlus

10007. Ettinger DS. Clinical implications of EGFR expression in the development and progression of solid tumors: focus on non-small cell lung cancer. The Oncologist. 2006; 11:358-73. http://www.ncbi.nlm.nih.gov/pubmed/16614231?dopt=AbstractPlus

10008. Sequist LV, Bell DW, Lynch TL et al. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small cell lung cancer. J Clin Oncol. 2007; 25:587-95. http://www.ncbi.nlm.nih.gov/pubmed/17290067?dopt=AbstractPlus

10009. Hanna S, Lilenbaum R, Ansari R et al. Phase II trial of cetuximab in patients with previously treated non-small cell lung cancer. J Clin Oncol. 2006; 24:5253-5257. http://www.ncbi.nlm.nih.gov/pubmed/17114658?dopt=AbstractPlus

10010. Ciardiello F and Tortora G. EGFR antagonists in cancer treatment. N Engl J Med. 2008; 358:1160-74. http://www.ncbi.nlm.nih.gov/pubmed/18337605?dopt=AbstractPlus

10011. AHFS Oncology Expert Committee reviewers’ comments (personal observations).

10012. Schiller JH, Harrington D, Belani C et al. Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med. 2002; 346: 92-8. http://www.ncbi.nlm.nih.gov/pubmed/11784875?dopt=AbstractPlus

10013. Socinski MA, Crowell R, Hensing TE, et al. Treatment of non-small cell lung cancer, stage IV: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132:277-289.

10014. Sandler A Gray R, Perry M et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med. 2006; 355:2542-50. http://www.ncbi.nlm.nih.gov/pubmed/17167137?dopt=AbstractPlus

10015. Chung KI, Shia J, Kemeny N et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005; 23:1803-10. http://www.ncbi.nlm.nih.gov/pubmed/15677699?dopt=AbstractPlus

10016. O'Byrne KJ, Gatzemeier U, Bondarenko I et al. Molecular biomarkers in non-small-cell lung cancer: a retrospective analysis of data from the phase 3 FLEX study. Lancet Oncol. 2011; 12:795-805. http://www.ncbi.nlm.nih.gov/pubmed/21782507?dopt=AbstractPlus

10017. Khambata-Ford S, Harbison CT, Hart LL et al. Analysis of potential predictive markers of cetuximab benefit in BMS099, a phase III study of cetuximab and first-line taxane/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2010; 28:918-27. http://www.ncbi.nlm.nih.gov/pubmed/20100958?dopt=AbstractPlus

10018. Pirker R, Pereira JR, von Pawel J et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012; 13:33-42. http://www.ncbi.nlm.nih.gov/pubmed/22056021?dopt=AbstractPlus

10019. Rosell R, Robinet G, Szczesna A et al. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol. 2008; 19:362-9. http://www.ncbi.nlm.nih.gov/pubmed/17947225?dopt=AbstractPlus

10021. Redman MW, Crowley JJ, Herbst RS et al. Design of a phase III clinical trial with prospective biomarker validation: SWOG S0819. Clin Cancer Res. 2012; 18:4004-12. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3409929&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/22592956?dopt=AbstractPlus

10022. Socinski MA, Evans T, Gettinger S et al. Treatment of stage IV non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl):e341S-68S. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=4694611&blobtype=pdf http://www.ncbi.nlm.nih.gov/pubmed/23649446?dopt=AbstractPlus

10023. European Medicines Agency. Withdrawal assessment report: Erbitux (cetuximab). Procedure No.: EMEA/H/C/000558/II/0043. 2012 Apr 19. From EMA website. http://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2012/11/WC500135081.pdf

10024. AHFS Final Determination of Medical Acceptance: Off-label use of cetuximab in combination with chemotherapy for the first-line treatment of advanced non-small cell lung cancer. Published April 2015.

Medical Disclaimer