Targeted Therapies + Chemo Show Activity in Recurrent/Metastatic Head And Neck Cancer

Biopsies of tumors and samples of blood were analyzed for correlative markers, including EGFR, gene copy number using fluorescence in situ hybridization (FISH), polymorphisms of intron 1 of the EGFR, and downstream EGFR pathway markers and mutations.

A total of 46 patients, median age 59, were enrolled from April to September 2006, and 42 patients were evaluable for response. About half of the patients had locoregional recurrence, one quarter had metastatic disease, and another one quarter had recurrent and metastatic disease.

All but nine of the patients had had previous chemotherapy or radiotherapy.

The complete response rate was 60%, with 24% achieving a complete response. Disease control was observed in 88% of the patients, with responses observed in both patients with locoregional recurrence and those with distant disease.

The median progression-free survival time was five months, and time to progression was six months. After a median follow-up of six months, seven patients are alive, and currently six of the seven are receiving treatment. Overall survival has not been reached.

The median number of cycles of cetuximab (15.5) and paclitaxel (14) administered was similar.

A total of 44 patients were evaluable for safety. Only one had Grade 3/4 febrile neutropenia. Neurologic toxicities were observed in three patients, severe rash in 11, and infusion-related reaction in three. No dose effect was observed.

Translational research using FISH found no relationship between response, survival, and gene amplification. Only three patients had positive FISH with a different type of response.

EGFR expression was positive in all patients. However, there was no relationship between EGFR expression and response, survival, or FISH.

We found a positive correlation between rash and response. There was no severe rash in patients with progressive disease, he said.

In conclusion, Dr. Hitt said that the combination of cetuximab and paclitaxel used in this study was feasible and associated with very encouraging activity in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Biologic markers, such as FISH analysis, do not seem to predict efficacy to this treatment combination. Further analysis of potential predictive factors or combinations of them is ongoing.

These results suggest that cetuximab and paclitaxel may play an important role for patients with recurrent head and neck cancer. Randomized trials are warranted, Dr. Hitt said.

The discussant for the study, Marshall Posner, MD, Medical Director of the Head and Neck Oncology Program at Boston’s Dana-Farber Cancer Institute, commented, Dr. Hitt’s study has a fairly impressive complete response rate of 24 percent. Unfortunately, the data are a little early, so progression-free survival, although five months, is really premature.