Cetuximab (C225) plus cisplatin/carboplatin is active in patients (pts) with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) porgressing on a same dose and schedule platinum-based regimen

Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 21, 2002

Presenter: J. Baselga
Presenter's Affiliation: Institut Goustave-Roussy, Villejuif, France
Type of Session: Scientific


    Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)who fail first line therapy have a very poor prognosis, with a response rate of <5% to second line therapy and a median survival of under 3 months. Epidermal Growth Factor Receptor (EGFR) and its ligands are frequently over-expressed by SCCHN. The overexpression of EGFR has been shown to convey a worse prognosis. C225 is an IgG, chimeric monoclonal antibody to EGFR that acts as a competitive inhibitor to prevent ligand binding and stimulate receptor internalization. In vitro data suggests a combined effect of C225 and cisplatin. C225 has been shown in previous phase I trials to be safe and well-tolerated. The objectives of this phase II study are to confirm the safety and tolerabilty and assess the efficacy of C225.

Materials and Methods

  • Eligible patients had SCCHN with documented local or metastatic progression after 2-4 cycles of cisplatin or carboplatin, and were not suitable for further local therapy.
  • Pts were treated with weekly C225, 400 mg/m2 initial dose, with 250 mg/m2 each subsequent dose, and the same dose of schedule of cisplatin/carboplatin that they had been receiving previously.


  • 96 pts were enrolled, 82% with stage IV disease, including 25 patients with metastases, and 18% stage III.
  • Prior to failing platinum-based therapy, 52 patients had received radiation therapy (XRT), 25 had prior chemotherapy and XRT, 4 had combined chemoradiotherapy, and 15 had no prior therapy. Prior to entry onto this study, 56 pts had had 5-fluorouracil and 11 had been treated with a taxane.
  • Side effects of any grade include 60% nausea/vomiting, 24% leukopenia, 16% mucositis, 5% elevated creatinine. 80% of pts developed a skin rash, including 3% grade 3-4, and 3% had an allergic reaction (none grade 3-4).
  • Of the 96 pts, 2 (2%) had a complete response (CR), 12 (12.5%) had a parial response (PR), and 38 patients had stable disease (SD) or minor responses lasting at least 6 weeks.
  • After strict radiographic review of all films, 21 pts were considered non-evaluable; documented progression could not be confirmed in 12, and 9 had technically inadequate pre-treatment imaging.
  • Of the remaining 75 patients, there was 1 CR, 7 PRs, and 27 SD.
  • 69 pts were analyzable for EGFR status; of 2 pts with "0" EGFR overexpression, 0 responded. Of 10 patients with "1+" overexpression, there was 1 response. Of 15 patients with "2+" overexpression , 2 responded, and of 42 patients with "3+" overexpression, 5 had a response.
  • By skin toxicity, disease control (CR + PR + SD) was 52% in patients who developed a rash and 35% in patients who did not.

Author's Conclusions

  • The trial confirms earlier phase I data that C225 is safe and well-tolerated.
  • C225 has activity against SCCHN, with an objective response rate (CR + PR) for the combination of C225/platinum of 14.6% in this study of recurrent/metastatic patients who had progressed on platinum alone.

Clinical/Scientific Implications

    The combination of C225 + platinum appears to have activity in this poor-prognosis population who progressed through therapy with platinum alone. The benefit seen may have been effected several ways; C225 may have alone caused all the responses, it may have acted in conjunction with the platinum agents, or it may have counteracted cellular mechanisms of platinum resistance. Alternatively, thought perhaps less likely, is the possibility that the benefit seen was due to the platinum alone. A randomized trial of cisplatin + placebo vs. cisplatin + C225 is also presented at this meeting (Burtness et al, abtract #901).

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