Cetuximab monotherapy is active in patients (pts) with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN):  Results of a phase II study.

Reviewer: Charles Wood, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 8, 2004

Presenter: J. Trigo
Presenter's Affiliation: Vall d'Hebron University, Barcelona, Spain
Type of Session: Scientific


  • There is no accepted standard therapy for recurrent squamous cell carcinoma of the head and neck.
  • Patients refractory to platinum-based chemotherapy rarely respond to second-line treatment (2.6%) and display a median survival of only 3 months.
  • Greater than 90% of SCCHN cancers express high levels of EGFR, and elevated levels are associated with both aggressive patterns of behavior and poor clinical outcome.
  • Cetuximab is an IG1 monoclonal antibody that competitively binds to the extracellular domain of EGFR and prevents binding of EGF and TGF-alpha, inhibiting activation of the intracellular tyrosine kinase.  This, in turn, leads to cell cycle delay, apoptosis, and decreased angiogenesis.
  • Earlier trials have demonstrated activity of cetuximab in EGFR-dependent tumors, and the antibody has shown synergism when delivered with platinum chemotherapy to xenograft tumors.
  • In addition, the combination of platinum and cetuximab was recently reported to improve the disease control rate in platinum-refractory head and neck cancers.
  • This phase II trial was conducted to evaluate the efficacy of cetuximab alone in patients with recurrent/metastatic head and neck cancer progressing on platinum-based chemotherapy regimens.


Materials and Methods

  • This was a phase II multicenter single arm trial involving patients with stage III/IV recurrent and/or metastatic SCCHN not suitable for local therapy.
  • Patients were required to have documented progression on or within 30 days of 2 to 6 cycles of platinum-based chemotherapy, bidimensionally measurable disease, a KPS greater than 60, and available tumor tissue for EGFR assessment.
  • Progresssion on platinum regimens was documented by individual investigators and later reviewed by an independent panel consisting of three radiologists and one medical oncologist.
  • Cetuximab was given initially at 400 mg/m2 followed by weekly dosing of 250 mg/m2 until disease progression with the option at that time to add the same platinum on which the patient had previously progressed.
  • The primary endpoint was response rate.
  • The secondary endpoints were duration of response, time to progression, overall survival, and safety profile.



  • 103 patients (84 male, 19 female) were enrolled between 9/02 and 12/03.
  • Median age was 57 years (range: 23 to 77).
  • Median KPS was 80.
  • Median time from diagnosis to study entry was 20 months.
  • Median follow-up was not disclosed.
  • 80% of patients had strongly positive (3+) EGFR staining.
  • 52% of patients had locally recurrent disease, and 48% of patients had metastatic disease.
  • Frequency of primary sites of disease:  pharynx (38%) > oral cavity (32%) > larynx (20%).
  • 69% of patients had a history of prior radiation.
  • Cisplatin/5-FU was the most commonly utilized chemotherapy regimen (54%).
  • Following independent review, only 66 out of 103 patients were judged to have had evidence of progression on platinum chemotherapy, and cohorts including the entire population (intent-to-treat) and progessive population (as confirmed by panel) were included in the analysis.
  • Concerning the intent-to-treat population, investigators judged there to be 0 patients with complete responses, 13% of patients with partial responses, 35% of patients with stable disease, and 52%patients with progressive disease.  The overall response rate was 13%, and the disease control rate was 45.6%.  The median time-to-progression was 2.3 months, the median overall survival was 5.9 months, and the 1 year overall survival was 12.7%.
  • In the progressing population, 12% of patients demonstrated a partial response.  The overall response rate was 12%, and the disease control rate was 45.5%.  The median time-to-progression was 2.1 months, the median overall survival was 5.5 months, and the 1 year overall survival was 8.2%.
  • Toxicity secondary to drug treatment included skin rash/acne (71%, 1% Grade 3), fatigue (25%, 4% Grade 3/4), nail changes (16%, 2% Grade 3/4), and fever/chills (18%).
  • There was no correlation between development of skin rash and response, nor was there correlation between EGFR intensity and response.  

Author's Conclusions

  • Cetuximab has significant activity in recurrent/metatstatic head and neck squamous cell carcinoma.
  • The benefit achieved with single agent cetuximab therapy was similar to the benefit observed in previous recurrent/metastatic head and neck cancer trials utilizing combination of cetuximab and platinum chemotherapy.
  • The agent is well-tolerated, with the majority of patients experiencing mild to moderate skin rash.
  • There is limited activity with combination cetuximab and platinum following failure of cetuximab alone.
  • Cetuximab appears to be a very promising treatment option in patients with recurrent/metastatic head and neck cancer.

Clinical/Scientific Implications

    This trial demonstrates the activity of cetuximab alone in recurrent squamous cell carcinoma of the head and neck.  Because the median survival is similar to that achieved with combination cetuximab and platinum chemotherapy, single agent cetuximab may be considered over combination cetuximab and platinum as second line systemic therapy due its vastly superior toxicity profile.  As this is the first trial examining cetuximab as a single agent in this population of patients, confirmation trials are certainly needed.  Compounding this necessity are concerns over the issue of patient selection in this study, as surprisingly few were confirmed to have progression on platinum regimens.  Fortunately, when analyzed as a distinct cohort, the results between the progressing population and intention-to-treat population were similar.  In addition, comparison trials with a variety of chemotherapy agents would further elucidate the role of cetuximab in head and neck carcinoma.  Furthermore, should cetuximab continue to display at least equivalent efficacy with agents currently utilized, future trials would be justified to determine its utility as first-line systemic therapy in head and neck carcinoma.   

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