Cetuximab
- Generic Name
- Cetuximab
- Brand Names
- Erbitux
- Drug Type
- Biotech
- CAS Number
- 205923-56-4
- Unique Ingredient Identifier
- PQX0D8J21J
- Background
Cetuximab is a recombinant chimeric human/mouse IgG1 monoclonal antibody that competitively binds to epidermal growth factor receptor (EGFR) and competitively inhibits the binding of epidermal growth factor (EGF). EGFR is a member of the ErbB family of receptor tyrosine kinases found in both normal and tumour cells; it is responsible for regulating epithelial tissue development and homeostasis. EGFR has been implicated in various types of cancer, as it is often overexpressed in malignant cells and EGFR overexpression has been linked to more advanced disease and poor prognosis. EGFR is often mutated in certain types of cancer and serves as a driver of tumorigenesis. In vitro, cetuximab was shown to mediate anti-tumour effects in numerous cancer cell lines and human tumour xenografts.
Approved by the FDA in February 2004 under the brand name ERBITUX, cetuximab is used for the treatment of head and neck cancer and metastatic, KRAS wild-type colorectal cancer, and metastatic colorectal cancer with a BRAF V600E mutation. It has also been investigated in advanced colorectal cancer, EGFR-expressing non-small cell lung cancer (NSCLC), and unresectable squamous cell skin cancer. Cetuximab is administered via intravenous infusion and is used as monotherapy or in combination with other chemotherapies, including platinum agents, radiation therapy, leucovorin, fluorouracil, and irinotecan.
- Indication
Cetuximab indicated for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy. It is indicated for treating a recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with fluorouracil. It is indicated for recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.
Cetuximab is also indicated for K-Ras wild-type, EGFR-expressing, metastatic colorectal cancer as determined by an FDA-approved test in combination with FOLFIRI, a chemotherapy combination that includes leucovorin, fluorouracil, and irinotecan; in combination with irinotecan in patients who are refractory to irinotecan-based chemotherapy; or as monotherapy in patients who have failed oxaliplatin- and irinotecan-based chemotherapy or who are intolerant to irinotecan.
Additionally, cetuximab is also indicated for metastatic colorectal cancer that is BRAF V600E mutation-positive (as determined by an FDA-approved test) in combination with encorafenib but only after prior therapy.
Cetuximab is not indicated for the treatment of Ras-mutant colorectal cancer or when the results of the Ras mutation tests are unknown.
- Associated Conditions
- Locally Advanced Squamous Cell Carcinomas of the Head and Neck (SCCHN), Metastatic Colorectal Cancer (CRC), Metastatic Squamous Cell Carcinoma of the Head and Neck (HNSCC), Regionally Advanced Squamous Cell Carcinoma of the Head and Neck, Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN)
SUNLIGHT Trial Highlights Importance of Sequential Therapies in Refractory Colorectal Cancer
• The SUNLIGHT trial demonstrated significant survival benefits when adding bevacizumab to trifluridine/tipiracil in refractory metastatic colorectal cancer, showing a 39% improvement in overall survival.
• Despite having three FDA-approved regimens for refractory colorectal cancer (trifluridine/tipiracil plus bevacizumab, fruquintinib, and regorafenib), many patients don't receive all available treatment options.
• Dr. John Marshall of Georgetown Lombardi Comprehensive Cancer Center emphasizes the need for personalized sequencing strategies and warns against non-medical factors influencing treatment decisions.
Novel Chemo-Immunotherapy Approach Shows Promise for Advanced HPV-Negative Head and Neck Cancer
• A Phase 2 clinical trial at UChicago Medicine demonstrated that combining nivolumab immunotherapy with chemotherapy led to tumor shrinkage in 53% of advanced HPV-negative head and neck cancer patients.
• The innovative treatment approach, which included response-adaptive chemo-radiation therapy, showed improved survival outcomes and reduced toxic side effects, particularly in patients who responded well to initial treatment.
• Higher PD-L1 expression levels were associated with better treatment responses, suggesting its potential as a biomarker for predicting treatment outcomes in this patient population.
NICE Reverses Decision, Approves Braftovi-Erbitux Combination for BRAF-Mutated Colorectal Cancer
• NICE has approved the combination of Braftovi (encorafenib) and Erbitux (cetuximab) for BRAF V600E-mutated metastatic colorectal cancer following an improved pricing agreement.
• The targeted therapy demonstrated significant clinical benefit in the BEACON CRC trial, showing a 9.3-month median overall survival compared to 5.9 months with standard chemotherapy.
• This chemotherapy-free regimen represents the first targeted treatment specifically approved for BRAF V600E-positive mCRC patients in Europe, offering new hope for this poor-prognosis population.
Purple Biotech Launches Phase 2 Trial of NT219 for Drug-Resistant Head and Neck Cancer
• Purple Biotech initiates Phase 2 trial of NT219, a novel dual-pathway inhibitor, in combination with pembrolizumab or cetuximab for treating recurrent/metastatic head and neck cancer.
• The study, led by Dr. Antonio Jimeno at University of Colorado, will evaluate NT219's potential to overcome tumor resistance in a $5 billion market where current treatments show only 15-20% response rates.
• NT219's unique mechanism targeting IRS1/2 and STAT3 pathways showed promising results in preclinical studies, demonstrating ability to reverse immunotherapy resistance in tumors.
BREAKWATER Trial: Braftovi-Erbitux Plus Chemotherapy Shows Promise in BRAF V600E Metastatic Colorectal Cancer
• Phase III BREAKWATER trial demonstrates efficacy of first-line combination therapy using Braftovi, Erbitux, and mFOLFOX6 chemotherapy in BRAF V600E mutated metastatic colorectal cancer patients.
• The study, led by MD Anderson Cancer Center researchers, represents a significant advancement in targeted therapy approaches for this specific genetic mutation in colorectal cancer.
• Results indicate potential new treatment pathway for patients with BRAF V600E mutations, who traditionally face poor prognosis with standard therapies.
Merck KGaA in Advanced Talks to Acquire SpringWorks Therapeutics; BridgeBio Secures EU Approval for ATTR Drug
• Merck KGaA confirms advanced acquisition discussions with SpringWorks Therapeutics, though critical conditions remain unmet and no binding agreement has been reached.
• BridgeBio Pharma's Beyonttra (acoramidis) receives European Commission approval for transthyretin amyloidosis with cardiomyopathy, triggering a $75 million milestone payment from Bayer.
• Biohaven's troriluzole receives FDA priority review for spinocerebellar ataxia, positioning it to potentially become the first approved treatment for this neurodegenerative disorder.
Fruquintinib Plus Trifluridine/Tipiracil Shows Promise in Pretreated Metastatic Colorectal Cancer
• A phase 2 trial combining fruquintinib and trifluridine/tipiracil demonstrated clinical activity in heavily pretreated metastatic colorectal cancer (mCRC) patients.
• The combination therapy achieved a median progression-free survival (PFS) of 6.33 months and a median overall survival (OS) of 18.4 months.
• The safety profile of the combination was acceptable, with treatment-related adverse events primarily being hematologic in nature.
• These findings suggest that fruquintinib plus trifluridine/tipiracil could be a potential alternative treatment option for mCRC patients who have progressed on prior therapies.
Evorpacept Shows Promise in HER2-Positive Gastric Cancer: Updated ASPEN-06 Data
• ALX Oncology's ASPEN-06 Phase 2 trial evaluates evorpacept, a CD47-blocker, in HER2-positive advanced gastric cancer patients who have been previously treated.
• Updated data from the ASPEN-06 trial were presented at the 2025 ASCO Gastrointestinal Cancers Symposium (ASCO GI).
• The virtual event hosted by ALX Oncology on January 23, reviewed the ASPEN-06 data, focusing on evorpacept's potential in immuno-oncology.
• The ASPEN-06 trial is a phase 2/3 study of evorpacept in patients with HER2-overexpressing gastric/gastroesophageal cancer.
FDA Approves Lumakras and Vectibix Combination for KRAS G12C-Mutated Metastatic Colorectal Cancer
• The FDA has approved Lumakras (sotorasib) combined with Vectibix (panitumumab) for treating KRAS G12C-mutated metastatic colorectal cancer in adults after prior chemotherapy.
• CodeBreaK 300 trial data showed the combination significantly improved progression-free survival compared to standard of care in chemorefractory patients.
• Patients on Lumakras and Vectibix had a median progression-free survival of 5.6 months, compared to 2 months on standard of care, with a 26% overall response rate.
• This approval provides a new targeted treatment option for a subset of colorectal cancer patients with limited alternatives, emphasizing the importance of biomarker testing.
Tempus Launches FDA-Approved xT CDx Test Nationwide for Comprehensive Solid Tumor Profiling
• Tempus AI has commercially launched xT CDx, an FDA-approved 648-gene NGS-based diagnostic test for solid tumor profiling, offering comprehensive genomic insights across multiple cancer types.
• The test serves as a companion diagnostic for identifying KRAS wild-type colorectal cancer patients suitable for cetuximab treatment and KRAS/NRAS wild-type patients for panitumumab therapy.
• Clinical validation demonstrated exceptional accuracy with 98.9% positive percent agreement and 100% negative percent agreement in hotspot variant detection across 416 tumor samples.
BioNTech Advances Oncology Pipeline with BNT327/PM8002 and mRNA Immunotherapies
• BioNTech is progressing BNT327/PM8002, a bispecific antibody, into global clinical trials for first-line small cell lung cancer and non-small cell lung cancer.
• The company plans to initiate additional trials combining BNT327/PM8002 with antibody-drug conjugates (ADCs) in 2025, expanding its combination strategy.
• BioNTech's mRNA cancer immunotherapy, autogene cevumeran, is being evaluated in a Phase 2 trial for muscle-invasive urothelial carcinoma in combination with nivolumab.
• Clinical data readouts are expected in 2025 and 2026 from multiple randomized trials of personalized and off-the-shelf mRNA cancer immunotherapy candidates.
FDA Grants Accelerated Approval to Krazati for KRAS G12C-Mutated Colorectal Cancer
• The FDA has granted accelerated approval to Krazati (adagrasib) in combination with Erbitux (cetuximab) for KRAS G12C-mutated colorectal cancer after prior chemotherapy.
• This approval is based on Phase 1/2 KRYSTAL-1 study data, demonstrating a 34% overall response rate and a median duration of response of 5.8 months.
• Krazati, developed by Bristol-Myers Squibb, now has a second indication, potentially boosting sales in the competitive KRAS inhibitor market.
• The accelerated approval is contingent upon confirmatory trial results, with the KRAS-targeting oncology market projected to reach $4 billion by 2029.
Nivolumab Plus Cisplatin-Radiotherapy Improves Disease-Free Survival in Advanced Head and Neck Cancer
• The Phase 3 NIVOPOSTOP trial demonstrated that adding nivolumab to standard cisplatin-radiotherapy significantly improved disease-free survival (DFS) in patients with resected, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
• The study showed a statistically significant and clinically meaningful improvement in DFS for patients receiving nivolumab compared to those receiving cisplatin-radiotherapy alone, marking a potential shift in the standard of care.
• A trend toward improved overall survival (OS) was observed with nivolumab, with final OS analysis pending, and the safety profile of nivolumab was consistent with previous studies.
• The findings suggest that adjuvant nivolumab could be practice-changing for high-risk LA-SCCHN patients, offering a new treatment option after surgery to reduce the risk of relapse.
FDA Approvals in 2024: Advancing Treatment Paradigms in Solid Tumors and Hematologic Malignancies
• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies.
• Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine.
• Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes.
• Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.
Pharma Stock Roundup: Novo Nordisk's Obesity Study Disappoints, Lilly's Zepbound Approved for Sleep Apnea
• Novo Nordisk's CagriSema obesity treatment showed a 22.7% weight loss in Phase III, falling short of the anticipated 25% reduction, impacting stock prices.
• Eli Lilly's Zepbound (tirzepatide) received FDA approval for moderate-to-severe obstructive sleep apnea (OSA), marking it as the first drug for obesity-related OSA.
• AstraZeneca and Daiichi Sankyo withdrew their EU application for Dato-DXd in non-small cell lung cancer (NSCLC) but pursue U.S. approval for EGFR-mutated NSCLC.
• Pfizer's Braftovi gained FDA approval in combination with Erbitux and mFOLFOX6 for first-line treatment of metastatic colorectal cancer with BRAF mutations.
FDA Approves New Therapies for Hemophilia, Colorectal Cancer, and Cystic Fibrosis
• The FDA approved Alhemo (concizumab) from Novo Nordisk for hemophilia A and B with inhibitors, offering a once-daily subcutaneous option.
• Pfizer's Braftovi (encorafenib) received accelerated approval as a first-line treatment for BRAF V600E-mutated metastatic colorectal cancer in combination with other therapies.
• Vertex Pharma's Alyftrek (vanzacaftor/tezacaftor/deutivacaftor), a new triplet therapy for cystic fibrosis, has been approved for patients aged six and older with responsive mutations.
• Hikma Pharma gains FDA approval for the first generic version of Novo Nordisk's Victoza (liraglutide) for treating type 2 diabetes.
Opdivo Plus Yervoy Demonstrates Improved Outcomes in MSI-H/dMMR Metastatic Colorectal Cancer
• The combination of Opdivo and Yervoy significantly reduced the risk of disease progression or death by 38% compared to Opdivo alone in MSI-H/dMMR mCRC patients.
• The CheckMate-8HW trial showed improved progression-free survival rates at 12, 24, and 36 months with the Opdivo/Yervoy combination versus Opdivo monotherapy.
• The objective response rate was higher with Opdivo plus Yervoy (71%) compared to Opdivo alone (58%), indicating a greater proportion of patients experienced tumor shrinkage.
• The safety profile of the Opdivo/Yervoy combination was consistent with previous findings, supporting its potential as a new standard of care.
Pfizer's Braftovi Combo Shows Survival Benefit in BRAF-Mutated Metastatic Colorectal Cancer
• Pfizer's Braftovi, combined with cetuximab and mFOLFOX6, significantly improved progression-free survival in metastatic colorectal cancer patients with BRAF V600E mutation.
• The BREAKWATER trial demonstrated a clinically meaningful improvement in overall survival with the Braftovi regimen compared to chemotherapy.
• The FDA granted accelerated approval to the Braftovi combination in December 2024, marking it as a first-line targeted therapy option.
• Pfizer plans to share the BREAKWATER data with regulatory authorities to support full approval and broader use of the Braftovi combination.
Biomarker-Guided Therapies Transform Treatment Landscape Across Multiple Cancers
• Recent advances in targeted therapies including KRAS, BRAF, and CLDN18.2 inhibitors are revolutionizing treatment approaches for pancreatic, colorectal, lung and gastric cancers through molecular profiling-guided precision medicine.
• Zolbetuximab plus chemotherapy demonstrated significant survival benefits in CLDN18.2-positive gastric cancer, while KRAS inhibitors showed promising response rates of 20-45% in pancreatic cancer patients with specific mutations.
• Multiple biomarker-targeted approaches including HER2, PD-L1, and FGFR2 are expanding treatment options across gastrointestinal cancers, though optimal sequencing strategies are still being determined.
Merus' Petosemtamab and Mersana's Emi-Le Show Promise in Cancer Treatment
• Merus' petosemtamab demonstrates a 36% overall response rate in recurrent/metastatic head and neck squamous cell carcinoma, with median overall survival of 11.4 months.
• Mersana Therapeutics' Emi-Le receives Fast Track designation for HER2-negative breast cancer, showing promising monotherapy activity in multiple tumors.
• Petosemtamab's clinical trials are ongoing, including phase 3 studies in HNSCC and expanded evaluation in metastatic colorectal cancer, with data updates planned for 2025.
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