TARCEVA FOR VULVAR CANCER

SAN FRANCISCO -- Twelve of 14 patients with locally advanced or recurrent vulvar cancer responded or had stable disease during neoadjuvant therapy with erlotinib (Tarceva), according to a study reported here.

The therapy was generally well tolerated, and the data hinted at a possible correlation between gene amplification and polysomy with response.

"Inhibition of epidermal growth factor receptor [EGFR] leads to responses in the neoadjuvant setting for women with vulvar squamous-cell carcinoma," Neil Horowitz, MD, of Dana-Farber Cancer Institute in Boston, said at the Society of Gynecologic Oncologists meeting.

"The results of this small study provide a potential foundation for future investigations for this malignancy," he added.

Standard therapy for vulvar carcinoma includes radical local excision with or without lymphadenectomy or neoadjuvant chemoradiation for locally advanced or unresectable disease.

Despite apparent disease control in many cases, the failure rate remains high, fueling interest in other therapies to improve long-term control, Horowitz said.

Several lines of evidence provided a rationale for clinical evaluation of erlotinib in vulvar cancer.

EGFR expression is altered in a variety of cancers, including elevated expression in 40% to 80% of vulvar squamous-cell carcinomas. EGFR gene amplification and high polysomy have been observed in vulvar cancer and have been associated with decreased survival and absence of high-risk human papillomavirus.

Moreover, Horowitz was co-author of a case report of "dramatic responses" to erlotinib in two elderly patients with locally advanced vulvar cancer (Gynecol Oncol 2007; 106: 628-30).

The rationale led to a phase II evaluation of erlotinib in two cohorts of patients, one with locally advanced or recurrent vulvar cancer and the other with metastatic disease.

The first cohort consisted of patients with T1-4 primary cancer or recurrent disease, treated neoadjuvantly with erlotinib 150 mg/d for four to six weeks, followed by definitive surgery or chemoradiation.

Patients in the second cohort had inoperable disease and received erlotinib 150 mg/d until disease progression or development of intolerable adverse events.

The primary objective was to determine the safety, efficacy, and tolerability of erlotinib. Secondarily, investigators explored possible correlations between EGFR gene amplification or polysomy and immunohistochemistry (IHC) staining with response.

The cohort that received neoadjuvant erlotinib consisted of 14 patients (13 evaluable), whose mean age was 75, with lesion size of 5.5 cm³. Nine patients had definitive surgery, and four had chemoradiation. The cohort with metastatic disease comprised eight women whose mean age was 65. All had recurrent disease.

The most common toxicities were diarrhea in 13 patients, rash in 13, and fatigue in 10. Most cases were grade 1-2. Nine patients had grade 3 toxicity, including three patients with electrolyte disturbances. The only grade 4 toxicity was a single case renal dysfunction.

Of the 21 evaluable patients, five had partial responses and seven had stable disease, all in the cohort that received neoadjuvant erlotinib. Four patients in the metastatic cohort had progression as best response, and the remaining four were unevaluable.

Ten patients in the neoadjuvant cohort had pre- and post-treatment results of IHC and fluorescence in situ hybridization. Three of the five responding patients had either trisomy or gene amplification, as did one patient with stable disease.

"A correlation between gene amplification and polysomy with response may exist, but these findings were predominately seen in post-treatment specimens, thus limiting its usefulness as a biomarker," said Horowitz.