Gefitinib Shows Single-Agent Activity in Patients With Bronchoalveolar Carcinoma

January 1, 2005

This supplement to Oncology News International includes 17 reportson clinical trials of targeted therapies used alone, in combination with chemotherapy,or in combination with each other in the treatment of non–small-cell lung cancer (NSCLC),bronchoalveolar carcinoma, glioblastoma multiforme, and renal cell carcinoma.Included is a report on a novel targeted agent recently approved for treatment of NSCLC.

SEATTLE-The largest prospectivetrial of patients with bronchoalveolarcarcinoma (BAC) showed thatgefitinib (Iressa) shows single-agentactivity and that women tend to survivelonger on the drug than men.Howard L. West, MD, of the SwedishCancer Institute in Seattle reportedresults of the Southwest OncologyGroup (SWOG) study S0126 (abstract7014).Although considered to be poorlyresponsive to conventional chemotherapy,BAC had not been widelystudied despite the fact that it is becomingmore common, especiallyamong young, nonsmoking women,Dr. West noted. "But there were anecdotalreports of rapid and remarkableradiographic responses to gefitinib,some quite long-lasting," he said.The study included 145 patients(136 evaluable) with advanced BAC,including 102 who had no prior chemotherapy.There was no requirementthat the patients' tumors express theepithelial growth factor receptor(EGFR), the drug's target.The main study objective was todetermine potential clinical, radiographic,pathologic, and molecularmarkers predictive of outcome underthe influence of gefitinib therapy. Theprimary study endpoint was overallsurvival. Secondary endpoints includedprogression-free survival (PFS), theresponse rate by RECIST (ResponseEvaluation Criteria in Solid Tumors)criteria, and toxicity. Patients weretreated with daily oral doses of gefitinib(500 mg) until there was evidenceof progression or prohibitivetoxicity.Dr. West reported that the responserates were 19% in previously untreatedpatients (including 6% completeresponses) and 9% in previously treatedpatients. "The clinical benefit rate(complete responses, partial responses,and stable responses) approached50% in both groups," he said. Mediansurvival was similar in both groups(10 to 12 months), as was median PFS(3 to 4 months)."There was a subset of patients withBAC who experienced prolonged survivalwith gefitinib. One of the mostimportant variables was gender. Womenhad a median survival of 19 monthscompared to 8 months for men," Dr.West said. "This relationship waspresent for both previously treatedand untreated patients."One year survival was about 50%in each subgroup. "A small group ofpatients continue to have no progressionbeyond 1 year," Dr. West said.Better Survival With RashDevelopment of any type of rashwas associated with significantly bettersurvival, and patients with grade 1rash had survival similar to those withgrade 2 or 3 rash. "There were noresponses among patients who did notdevelop a rash," Dr. West said.Patients who had never smoked alsohad better survival. Median survival ofnonsmokers has not yet been reached.Toxicity was predominantly an acneiformrash (82%; 11% grade 3 or 4) anddiarrhea (69%; 20% grade 3, no grade4). Fifteen patients (11%) came off trialbecause of toxicity. Just over one-thirdhad dose reduction to 250 mg/day.Pulmonary toxicity has been a concernwith this drug, and there werethree deaths among patients in thisstudy that were considered to be probablytreatment-related. "In each case,the patient had a worsening of diffusepulmonary infiltrates and had toxemiaof unclear etiology, although itmay represent interstitial lung disease,"Dr. West told Oncology NewsInternational.