• 8/30/2004
  • James A. Bonner, MD
  • 40th ASCO Annual Meeting

By blocking the epidermal growth factor receptor (EGFR), cetuximab (Erbitux, ImClone and Bristol-Myers Squibb) may be a valuable treatment option for patients with head and neck cancer.

In several studies presented here at the 40th ASCO Annual Meeting, cetuximab produced results as a single agent or in combination with other drugs or radiation in patients with locoregionally advanced and recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Adding cetuximab to radiation therapy nearly doubled survival for patients with locoregionally advanced SCCHN in a phase-3 international trial.
“The use of cetuximab and radiation therapy may become an excellent choice of therapy for this group of patients,” said James A. Bonner, MD, the chairman and Merle M. Salter Professor of Radiation Oncology at the University of Alabama at Birmingham.

Most SCCHN cells overexpress the EGFR, which is associated with aggressive tumor behavior and poor clinical outcome. Bonner and his colleagues hypothesized that treating patients with EGFR-blocking drugs, like cetuximab, could potentially make these cancers more sensitive to radiation.
The researchers compared survival between 211 patients who received high-dose radiation therapy plus cetuximab and 213 patients who received radiation therapy alone. Median survival was nearly twice as great in the cetuximab group: 54 months versus 28 months. At one year, 69% of patients in the cetuximab-radiation arm had achieved locoregional control, compared with 59% of patients in the radiation-alone arm. More of the cetuximab patients were alive at two years and three years, compared with the radiation-only group. The cetuximab regimen was well tolerated, with skin reactions noted as the most common adverse effect.

Two other studies looked at cetuximab in patients with advanced recurrent or metastatic SCCHN. A multicenter phase-2 study evaluated the response rate of single-agent cetuximab in 103 patients with advanced recurrent and/or metastatic SCCHN not suitable for local therapy and refractory to platinum-based chemotherapy. The overall response rate was 12.6%, all partial responses. When the rate of stable disease was considered, the disease-control rate increased to 45.6%. The median time to progression was 2.3 months, with a median survival of 5.9 months. Fifty-three patients experienced progressive disease and went to receive cetuximab in combination with platinum-based chemotherapy; 25 patients were not assessable. Among these patients, there were 14 patients with stable disease and 14 patients with progressive disease. Median time to progression in this group was 50 days. Grade-3/4 adverse events included fatigue in 4% of patients, vomiting in 2% of patients and nausea, diarrhea and an acne-like rash each in 1% of patients. There was one treatment-related death due to infusion reaction.

A randomized phase-1 study evaluated the safety and tolerability of cetuximab in combination with one of three doses of 5-fluorouracil and either cisplatin or carboplatin (Paraplatin, Bristol-Myers Squibb) in 52 patients with recurrent and/or metastatic SCCHN. The overall response rate for 47 evaluable patients was 48.9%, according to the study’s abstract. The response rate included two complete responses and 21 partial responses. When stable disease was considered, the disease control rate was 83.0%.
Skin reactions were the most frequent adverse event of any grade. Grade-3/4 adverse events occurring in at least 10% of patients who received cisplatin were leukopenia, asthenia, nausea/vomiting, mucositis, anemia and thrombocytopenia. Severe adverse events occurring in at least 10% of patients who received carboplatin were leukopenia, thrombocytopenia, asthenia and mucositis.

Source: Bonner JA, et al. Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck: a phase 3 study of high dose radiation therapy with or without cetuximab. Abstract #5507.
Trigo J, et al. Cetuximab monotherapy is active in patients with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck: results of a phase 2 study. Abstract #5502.
Humblet Y, et al. Phase 1 study of cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Abstract #5513.
All presented at the 40th ASCO Annual Meeting. June 5-8, 2004. New Orleans