ERCC1 mRNA-based randomized phase III trial of docetaxel (doc) doublets with cisplatin (cis) or gemcitabine (gem) in stage IV non-small-cell lung cancer (NSCLC) patients (p)

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Abstract
7002 Background: ERCC1 is a leading component of NER in repairing cis damage. Increased ERCC1 mRNA levels have been related to resistance to platinum-based chemotherapy. We hypothesized that p with high tumor ERCC1 levels would have a significantly better response with a non-cis combination. Methods: Stage IV NSCLC p with available tumor biopsy samples were randomized 1:2 to the control arm (A) or the genotypic arm (B). Arm A received doc/cis. In arm B, ERCC1 expression was examined by TaqMan assay (Response Genetics, Los Angeles, CA); p with low levels received doc/cis (arm B1) and p with high levels received doc/gem (arm B2). ERCC1 expression was examined retrospectively in arm A. At September 2004, 342 of a projected 440 p were included. Results: Data on 192 p are available: 80% male; 33% PS 0. Logistic regression of response showed that arm B1 had better response than A (P=0.04) and than B2 (P=0.02). Median ERCC1 levels were lower in responders in arms A and B1, but higher in responders in arm B2. When ERCC1 mRNA levels were divided into quartiles, p in the lowest quartile attained 70% response in arm B1, while the highest response in arm B2 was observed in the highest quartile (43%). Median ERCC1 levels were lower in adenocarcinomas (adeno) than in squamous cell carcinomas (SCC) (P=0.03). Median survival (MS) in arms A and B1 was 14 months (m) for 49 p in the lowest quartile vs 8 m for 19 p in the highest quartile (P=0.03). MS in arm B2 was 9.5 m in the two highest quartiles. Conclusions: Lower ERCC1 mRNA levels confer better response to doc/cis, while there is a tendency for p with higher levels to respond better to doc/gem than those with lower levels. Complete data on 300 p will be presented. No significant financial relationships to disclose.

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