NSCLC Patients Who Have Never Smoked Gain Significantly When Erlotinib Is Added to Chemotherapy

Oncology NEWS International Vol 14 No 1, Volume 14, Issue 1

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.

NEW YORK-Non-smallcelllung cancer (NSCLC) patients whohave never smoked gain significantlywhen erlotinib (Tarceva) is added totheir chemotherapy regimens, accordingto two recent studies reported byinvestigators from Memorial Sloan-Kettering Cancer Center (MSKCC).Mark G. Kris, MD, reported datafrom a phase II trial in patients withbronchoalveolar carcinoma (BAC)showing that response to erlotinib wassignificantly higher in nonsmokers andin patients who had adenocarcinomaswith BAC features (abstract 7062). Heand colleagues from MSKCC andVanderbilt-Ingram Cancer Center,Nashville, analyzed pretreatment factorsassociated with radiographic responseafter erlotinib in patients withany BAC features in tumor specimens.Of the 83 patients treated with erlotinib150 mg po daily, 27% hadnever smoked. Among 78 evaluablepatients, 19 (24%) had partial responses(PR). Seven of the responses areongoing, with a range of 1+ to 21+months. Median response duration is12 months.Median patient age was 65 years(range 33-85); 64% were women; and26% had prior chemotherapy. Pathologieswere 24% "pure" BAC, 75% adenocarcinomawith BAC features, and1% BAC with focal invasion.More Likely to RespondResponse correlated with smoking.The PR rate was 45% in never smokersvs 18% in smokers. Patients with verylittle tobacco exposure (1 to 5 packyears) also did well: three of six hadpartial responses. "This suggests themolecular target of erlotinib is lesslikely to be influenced by tobacco exposure,"Dr. Kris said.The 1 year survival is 58% (95% CI44% to 76%). Median survival has notbeen reached."Patients who benefit have adenocarcinomaswith BAC, not pure BAC,"Dr. Kris told ONI (see Table 1). Thosewho had never smoked did better,even within the BAC cohort.

"Because they are more likely torespond to HER1/epithelial growthfactor receptor (EGFR) tyrosine kinaseinhibitors, patients who neversmoked and those with adenocarcinomawith BAC features need to be accountedfor in non-small-cell lungcancer trials," Dr. Kris said. "Theseobservations can focus laboratory investigationsto discover why NSCLCin individuals with little or no cigaretteexposure or with adenocarcinomawith BAC features are more likelyto be sensitive to EGFR tyrosine kinaseinhibitors."Owing to the relatively small numbersof patients in this trial, correlationof smoking status with other patientcharacteristics also needs furtherstudy, according to investigators.TRIBUTE Subgroup AnalysisIn a related study, a subgroup analysisof the TRIBUTE study (see page2) found that although adding erlotinibto carboplatin (Paraplatin)/paclitaxel did not confer a survivaladvantage over chemotherapy alonein all enrolled NSCLC patients, it didmarkedly prolong survival in neversmokers (abstract 7061). Patients inthe erlotinib arm who reported neversmoking had improved overall survivalvs never smoking patients whoreceived chemotherapy alone; mediansurvival was 23 vs 10 months (HR0.49; 95% CI 0.28-0.85)(see Figure 1)."This suggests that erlotinib mayaugment the effect of chemotherapyin specific subsets of NSCLC patients,"reported Vincent A. Miller, MD, alsoof MSKCC. "Why never smokers aremore sensitive to erlotinib is underinvestigation, but this may be due inpart to the recent observation thattumors arising in never smokers aremore likely to harbor mutations in theEGFR tyrosine kinase domain."TRIBUTE was a placebo-controlledstudy of patients with previously untreatedadvanced NSCLC who wererandomized to erlotinib 150 mg/dayor to placebo, with six cycles of carboplatin/paclitaxel followed by maintenancemonotherapy.