Erlotinib Controls NSCLC in More Than 60% of Elderly Patients With Advanced NSCLC in Phase II Trial

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.

BOSTON-Erlotinib (Tarceva)produced a disease control rate of63.2% in elderly patients with advancednon-small-cell lung cancer(NSCLC), and at a median follow upof 6 months, 33 of the 38 study patientswere still alive. Bruce E. Johnson,MD, of Dana-Farber Cancer Institutein Boston presented preliminary datafrom the phase II study (abstract 7080)."Erlotinib demonstrated encouragingantitumor activity in patientsover age 70 who had previously untreated,advanced NSCLC. Responseswere observed in advanced disease andin bronchoalveolar carcinoma(BAC)," Dr. Johnson said.Elderly patients are more vulnerableto chemotherapy-related toxicitythan younger patients. Dr. Johnsonexplained that erlotinib was an attractivecandidate in this setting becauseof its activity and generally low sideeffectprofile in the treatment ofpatients who have failed prior chemotherapy.Nearly All Were SmokersThis ongoing single center phase IIstudy is enrolling patients ≥ 70 yearsof age who are chemotherapy-naiveand have stage IIIB (with malignanteffusion) or stage IV NSCLC and performancestatus (PS) of 0 to 2. Patientsare treated with oral erlotinib150 mg/d until evidence of diseaseprogression or toxicity.The primary study endpoint is mediansurvival. Secondary endpoints includeresponse rate, quality of life,changes in fluorodeoxyglucosepositronemission tomography (FDGPET)imaging, and analysis of theEGFR signaling pathway from pretreatmenttumor specimens.Dr. Johnson reported data for 38patients who were evaluable for toxicityand response at the time of thispresentation. Median age was 76 years,with a range of 70 to 86. Most patients(28/38) were PS 1. Nearly all (30/38)were former smokers, and two werecurrent smokers.Fifty-six percent had adenocarcinomas;14% had squamous cell carcinomas;11% had adenocarcinomas withBAC features; 11% had BAC; 11% hadunclassified NSCLC unclassified; and2% had large cell carcinomas.Five patients (13.1%) had partialresponses with a median duration of8.0 months, and 19 (50%) had diseasestabilization with a median durationof 3.5 months. "Survival and FDGPETimaging outcomes are too earlyto evaluate," Dr. Johnson said.Rash affected 77% of patients butwas grade 1 or 2 in 92% of those affected."All of the responding patientsdeveloped rash," Dr. Johnson noted.Grade 1 or 2 diarrhea developed in61% of patients. Grade 3 or worsetoxicities included pneumonitis(6.5%) and lacrimation (3.2%). Dr.Johnson reported that one patient diedfrom drug toxicity (pneumonitis).Three patients (8.5%) were dose reducedowing to toxicity, and threepatients discontinued treatment."Erlotinib appears to be well toleratedand demonstrates encouragingactivity in patients ≥ 70 years of agewith previously untreated advancedNSCLC. Accrual is continuing to 60patients," Dr. Johnson said.