Purpose: We evaluated the efficacy of gemcitabine versus gemcitabine and carboplatin in patients with advanced non–small-cell lung cancer (NSCLC) and a performance status (PS) of 2 and assessed if tumoral RRM1 and ERCC1 protein levels are predictive of response to therapy.

Patients and Methods: A randomized phase III trial was conducted in community-based oncology practices. Tumor specimens were collected a priori and shipped to a single laboratory for blinded determination of in situ RRM1 and ERCC1 protein expression levels by an automated quantitative immunofluorescent-based technology.

Results: One hundred seventy patients were randomly assigned. Overall median survival was 5.1 months for gemcitabine and 6.7 months for gemcitabine and carboplatin (P = .24). RRM1 (range, 5.3 to 105.6; median, 34.1) and ERCC1 (range, 5.2 to 131.3; median, 34.7) values were significantly and inversely correlated with disease response (r = -0.41; P = .001 for RRM1; r = -0.39; P = .003 for ERCC1; ie, response was better for patients with low levels of expression). A model for response prediction that included RRM1, ERCC1, and treatment arm, was highly predictive of the treatment response observed (P = .0005). We did not find statistically significant associations between survival and RRM1 or ERCC1 levels.

Conclusion: Single-agent chemotherapy remains the standard of care for patients with advanced NSCLC and poor PS. Quantitative analysis of RRM1 and ERCC1 protein expression in routinely collected tumor specimens in community oncology practices is predictive of response to gemcitabine and gemcitabine and carboplatin therapy. Oncologists should consider including in situ expression analysis for these proteins into their therapeutic decisions.