|
The addition of erlotinib to standard chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck produced a 66% response rate in a phase III trial.
"This is the first study to report on erlotinib combined with chemotherapy in incurable head and neck cancer," the lead author, Dr. Edward S. Kim of the University of Texas M.D. Anderson Cancer Center in Houston, announced.
Acknowledging that historical data show that chemotherapy is not very effective in head and neck cancer, Dr. Kim proposed that epidermal growth factor receptor (EGFR) inhibitors such as erlotinib (Tarceva) might improve outcome. "EGFR inhibitors do have activity in head and neck cancer," he said.
Prior research has suggested that EGFR inhibitors work synergistically with chemotherapy to enhance cell cycle arrest. A phase I trial showed efficacy with chemotherapy and erlotinib (Clin. Cancer Res. 2006;12:7406-13).
Dr. Kim and his colleagues conducted the open-label study of 50 patients (48 evaluable) with previously untreated recurrent or metastatic disease. Nearly two-thirds had locoregional disease; over one-third had metastatic disease.
Patients received docetaxel 75 mg/m² and cisplatin 75 mg/m² every 3 weeks along with erlotinib 150 mg daily for up to six cycles. After six cycles of chemotherapy, they could continue on erlotinib until disease progression. Most also received growth factor support.
The overall response included complete response in 4 patients and partial response in 28. Also, 13 patients had stable disease. Following two treatment cycles, only threee patients progressed. After 19 months of follow-up, median overall survival was 11 months and median progression-free survival was 6 months. One-year survival was 48%.
In the subgroup of 25 patients with recurrent disease in a prior radiated field, the response rate was 56%, including complete responses in 3, partial responses in 11, and stable disease in 8.
"We were encouraged when we saw the response rates," Dr. Kim remarked.
Neutropenia was the most common grade 3-4 toxicity, reported by 64% of patients. Only 10% experienced grade 3-4 febrile neutropenia, however. Grade 3-4 anemia, dehydration, diarrhea, and nausea were each reported by 14%.
The discussant, Dr. Marshall Posner of Dana Farber Cancer Institute in Boston, commented that the study showed "a low" 8% complete response rate but an "impressive" 66% overall response rate, and a "fairly impressive" 1-year survival of 48%. He noted that, except for neutropenia, toxicity was mild for an every-3-week regimen.
Kim E.S. et al. Final results of a phase II study of erlotinib, docetaxel, and cisplatin in patients with recurrent/metastatic head and neck cancer. Abstract 6013.
Commentary |
This study is interesting because the response rates with erlotinib as a single agent in head and neck disease are a disappointing 4%-5%. That being said, Kim et al. report excellent response and survival rates by combining erlotinib with docetaxel and cisplatin for 6 months, and then continuing the erlotinib until disease progression. The triple therapy produced a 66% response rate, and then continued to keep the disease in check for a 1-year survival of 48%. That is a big victory for patients who cannot tolerate long periods of toxic combination chemotherapy. It needs to be pointed out that single-agent docetaxel produced a 40% response rate in phase II studies, and this rate may be even higher when docetaxel is combined with cisplatin. Investigators at M.D. Anderson showed prolonged survival with this combination years ago (J. Clin. Oncol. 2002;20:1593). Thus, it is unclear what role erlotinib actually played in the long-term survival of these patients. We need a randomized trial to determine whether this triple therapy improves progression-free and overall survival over docetaxel/cisplatin alone. — Marshall R. Posner, M.D.
|