NEW YORK-Non-smallcell lung cancer (NSCLC) patients who have never smoked gain significantly when erlotinib (Tarceva) is added to their chemotherapy regimens, according to two recent studies reported by investigators from Memorial Sloan- Kettering Cancer Center (MSKCC). Mark G. Kris, MD, reported data from a phase II trial in patients with bronchoalveolar carcinoma (BAC) showing that response to erlotinib was significantly higher in nonsmokers and in patients who had adenocarcinomas with BAC features (abstract 7062). He and colleagues from MSKCC and Vanderbilt-Ingram Cancer Center, Nashville, analyzed pretreatment factors associated with radiographic response after erlotinib in patients with any BAC features in tumor specimens. Of the 83 patients treated with erlotinib 150 mg po daily, 27% had never smoked. Among 78 evaluable patients, 19 (24%) had partial responses (PR). Seven of the responses are ongoing, with a range of 1+ to 21+ months. Median response duration is 12 months. Median patient age was 65 years (range 33-85); 64% were women; and 26% had prior chemotherapy. Pathologies were 24% "pure" BAC, 75% adenocarcinoma with BAC features, and 1% BAC with focal invasion. More Likely to Respond Response correlated with smoking. The PR rate was 45% in never smokers vs 18% in smokers. Patients with very little tobacco exposure (1 to 5 pack years) also did well: three of six had partial responses. "This suggests the molecular target of erlotinib is less likely to be influenced by tobacco exposure," Dr. Kris said. The 1 year survival is 58% (95% CI 44% to 76%). Median survival has not been reached. "Patients who benefit have adenocarcinomas with BAC, not pure BAC," Dr. Kris told ONI (see Table 1). Those who had never smoked did better, even within the BAC cohort. "Because they are more likely to respond to HER1/epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors, patients who never smoked and those with adenocarcinoma with BAC features need to be accounted for in non-small-cell lung cancer trials," Dr. Kris said. "These observations can focus laboratory investigations to discover why NSCLC in individuals with little or no cigarette exposure or with adenocarcinoma with BAC features are more likely to be sensitive to EGFR tyrosine kinase inhibitors." Owing to the relatively small numbers of patients in this trial, correlation of smoking status with other patient characteristics also needs further study, according to investigators. TRIBUTE Subgroup Analysis In a related study, a subgroup analysis of the TRIBUTE study (see page 2) found that although adding erlotinib to carboplatin(Drug information on carboplatin) (Paraplatin)/ paclitaxel(Drug information on paclitaxel) did not confer a survival advantage over chemotherapy alone in all enrolled NSCLC patients, it did markedly prolong survival in never smokers (abstract 7061). Patients in the erlotinib arm who reported never smoking had improved overall survival vs never smoking patients who received chemotherapy alone; median survival was 23 vs 10 months (HR 0.49; 95% CI 0.28-0.85)(see Figure 1). "This suggests that erlotinib may augment the effect of chemotherapy in specific subsets of NSCLC patients," reported Vincent A. Miller, MD, also of MSKCC. "Why never smokers are more sensitive to erlotinib is under investigation, but this may be due in part to the recent observation that tumors arising in never smokers are more likely to harbor mutations in the EGFR tyrosine kinase domain." TRIBUTE was a placebo-controlled study of patients with previously untreated advanced NSCLC who were randomized to erlotinib 150 mg/day or to placebo, with six cycles of carboplatin/ paclitaxel followed by maintenance monotherapy.