Gefitinib Shows Promise in Never Smokers With Advanced Lung Adenocarcinoma

GOYANG, Korea-Singleagent gefitinib(Drug information on gefitinib) (Iressa) appears to be a very promising treatment in Korean patients who have never smoked and have advanced or metastatic adenocarcinoma of the lung, according to the findings of a phase II trial that tested the targeted drug as first-line therapy. The results of the trial warrant further study of gefitinib in this population, said Dae Ho Lee, MD, who led the trial at the National Cancer Center in Goyang, Gyeonggi, Republic of Korea (abstract 7072). Drug of Choice The discussant of this abstract, Roman Perez-Soler MD, chief of the oncology division at the Montefiore Medical Center, New York, called the results "very impressive," adding that he is "convinced that gefitinib was definitely the drug of choice for this patient population." The trial enrolled 55 patients, 51 of them women. All had previously untreated stage IIIb or IV adenocarcinoma and no smoking history. Twenty of the patients had evaluable brain metastases. Treatment consisted of gefitinib at 250 mg daily for 28 days until disease progression or unacceptable toxicity. Objective tumor responseswere assessed every two cycles. Overall, 61.1% of the patients had a response to the drug; partial responses were seen in 57.4% of patients and complete responses in 3.7% (Table 1). About 11.1% had stable disease. Of the 20 patients with brain metastases, 12 had responses in both intracranial and extracranial lesions, and one patient who had a "dramatic response" in extracranial lesions showed only stable disease in intracranial lesions, Dr. Lee said. Analysis of the responsesfound no correlation with sex, performance status, or bronchioalveolar features. The drug showed a good toxicity profile, with no significant hematologic adverse effects. Serious toxicities included a grade 3 rash in two patients; a grade 3 elevated liver enzyme in three patients; and grade 3 asthenia, vomiting, and neuropathy, each in one patient. Assessing EGFR Status In his discussion, Dr. Perez-Soler said that one remaining question is related to patient selection: Would knowing the mutational status of the patients' epidermal growth factor receptors (EGFRs) or numbers of EGFR gene copies help in selecting patients who would benefit from gefitinib? "I understand that these analyses will be done," he said, "and it will be nice to see whether [improved patient selection] can actually increase the survival rate." To follow up on this trial, the researchers have initiated a phase III study of gefitinib vs standard chemotherapy- gemcitabine(Drug information on gemcitabine) (Gemzar) and cisplatin(Drug information on cisplatin)-in this population. That trial will include correlative studies of EGFR mutations, Dr. Lee said.