gms | German Medical Science

Background: Induction therapies have been shown to potentially improve long term survival especially in patients with histologic response after induction. As <30% of pts respond with favorable pathologic tumor regression to chemotherapy there is an urgent need to increase effectivity of CTx. Although erlotinib and CTx combinations have failed in unselected patients to improve response rates and survival, they might be synergistic in specific subgroups (never smokers, EGF-R mutated pts, EGF-R gene amplification) with the highest erlotinib response rates. Tumor profiling might be helpful in identifying further subgroups of pts with high response rates to erlotinib and erlotinib/CTx.

Methods: Primary aim of the CHALLENGE phase II trial is to determine pathological response rate (RR), evaluated with morphometry, of CTx +/- erlotinib and to correlate this with genetic tumor markers. This trial plans to recruit 116 pts with pathologically proven N2/N3 NSCLC. At mediastinoscopy or VATS, fresh lymph nodes and/or primary tumor samples are taken for microarray analysis and further tumor profiling. Pts are staged with CT, PET, and are induced for 6 weeks with erlotinib 150 mg/d p.o.. Erlotinib response is assessed by CT and PET. CT non-progressers receive combined erlotinib/CTx, CT-progressors only CTx (all pts 3 cycles of gemcitabine/cisplatin). After 3 cycles, pts are restaged by CT and PET and are evaluated for surgery. Resection specimens are studied morphometrically for pathologic response and are subjected to microarray analyses and further tumor profiling. Adjuvant radiotherapy and 1 year erlotinib maintenance therapy (in erlotinib responders) is given post-op.

Results: As of yet, 14 pts have been screened, 7 cN2/N3 pts dropped out because of non-involved lymph nodes (5/7), lymph node without reach (1/7) and M1 status by PET (1/7). 7 pts were registered and started induction therapy with erlotinib. 7/7 pts are evaluable for erlotinib response assessment, 4/7 were erlotinib non-progressors in CT. 7/7 pts have been resected, 3 after erlotinib-erlotinib/CTx, 4 after erlotinib-CTx, 6/7 R0 and good morphometric tumor regression, 1/7 R1. No significant toxicity necessitating dose reduction was observed.

Conclusions: This is the first prospective tumor profiling study in NSCLC III where material is ascertained before induction therapy. Tumor profiling data as well as imaging and metabolic response data after erlotinib therapy might have the potential to identify further subgroups benefiting from EGF-R inhibitor therapy.