Background: Somatic mutations in the tyrosine kinase (TK) domain of the EGFR gene have been described in pts with NSCLC, particularly in adenocarcinoma, and are associated with dramatic responses to TK inhibitors. Most mutations are located in exons 19 (deletions) and 21 (missense mutations). The association of cetuximab (Erbituxâ„¢) response with EGFR mutations has not yet been reported. The addition of cetuximab, a monoclonal antibody targeting the EGFR, to CV, a standard chemotherapy in NSCLC, was evaluated in the first-line treatment of advanced NSCLC pts. We have examined the presence of EGFR mutations in exons 19 and 21 in pure tumor genomic DNA derived from paraffin-embedded tissue from 40 of 86 pts included in this trial for whom tumor tissue was available. More samples from the rest of the patients will be analyzed. Methods: All pts were chemonaive and received C 80 mg/m2 d1 and V 25 mg/m2 d1 and 8, q3 weeks and were randomized to also receive cetuximab 400 mg/m2 week 1 and 250 mg/m2 weekly thereafter (arm A) or not (arm B). Tumor genomic DNA was obtained by laser capture microdissection. Sequencing was performed with the ABI Prism 3100 DNA Analyzer. The human NSCLC cell line (PC9), derived from an adenocarcinoma (Kyushu Cancer Center, Fukuoka, Japan), was also examined. Results: Enrollment was completed with a total of 86 pts: 43 (10 f, 33 m) in arm A and 43 (12 f, 31 m) in arm B. The following pt characteristics were similar in both treatment arms: median age of 58 y (34-75); median KPS 90; 92% of pts had stage IV NSCLC, 42% had adenocarcinoma and 42% had squamous cell carcinoma. Confirmed response rates were 35% in arm A (43 evaluable pts) and 28% in arm B (43 evaluable pts). TTP was 4.8 months in arm A and 4.2 months in arm B. Median survival was 8.3 months in arm A and 7 months in arm B. EGFR mutations were found only in 3/12 adenocarcinomas (25%) (Table 1). The patient harboring an EGFR mutation who received cetuximab remained in PR for an exceptionally prolonged period (22.5 months). Conclusion: Cetuximab was demonstrated to be feasible in combination with chemotherapy. EGFR mutations were observed only in lung adenocarcinoma. A potential benefit for cetuximab may be derived in these pts.
Full conference title:
15th Annual Focus on Fungal Infections
- FFI 15th (2005)