Phase II study of erlotinib in chemo-naive women with advanced pulmonary adenocarcinoma
7591 Background: Erlotinib is associated with a survival benefit over placebo for pts with advanced NSCLC who had received 1–2 prior regimens. Its role as initial therapy in clinically defined subgroups or in pts prospectively tested for EGFR mutations is less clear. Methods: Chemotherapy-naive women with adenocarcinoma, stage IIIB/IV, PS 0–1, who had formerly or never smoked, were enrolled and treated with erlotinib 150 mg PO daily, until the time of disease progression or unacceptable toxicity. Response rate was the primary endpoint. Secondary endpoints included overall survival, progression-free survival and toxicity. Tumor tissue adequate for genomic analysis was mandated and prospectively collected for determination of EGFR and KRAS mutations by direct sequencing. Results: From 11/04 to 10/06, 40 women were treated. Demographics: median age 65 yrs (range 36–87); 38 white, 1 black, 1 Asian; 30% PS 0, 70% PS 1; 20% BAC or adenoCA w/ predominant BAC features, 80% adenoCA w/o BAC features; smoking status: 63% former, 37% never. Toxicity: Rash (95%; 30% grade 3) and diarrhea (73%; 10% grade 3) were the most common toxicities. 50% of pts developed toxicity of grade 3 or greater. 5 pts were discontinued due to toxicity, with 2 deaths that were possibly treatment-related: 1 DIC, 1 hepatic failure. There were also two pts with PE (one fatal). Response: CR 0, PR 12 (30%), SD 11 (28%), and PD 10 (25%), 7 not evaluable. To date, 27 patients have progressed, with 14 deaths. Median PFS was 5.6 months; median overall survival has not yet been reached and exceeds 23 months. Of 32 patients sequenced for EGFR to date, there were 9 exon 19 deletions, 3 L858R mutations, and 1 exon 20 insertion. For the 12 pts prospectively determined to have classic EGFR mutations, RR was 75% (9 PR, 2 SD, 1 not evaluable). Of 15 pts w/ wild-type EGFR, only 1 response (7%) was achieved. The pt w/ the exon 20 insertion developed PD. Of 28 pts evaluated to date for KRAS, 6 KRAS mutations were found, w/ no responses in this group (2 PD, 4 SD). Conclusions: Preliminary results suggest that first-line erlotinib monotherapy may be a useful treatment strategy for women with adenocarcinoma and a limited smoking history. Response rate is particularly impressive for those subjects prospectively found to have an EGFR mutation, and poor for those with KRAS mutations. No significant financial relationships to disclose.