肺癌基因突变于化疗疗效分析要点.ppt

Molecular Pathology of Lung Cancer Ming Sound Tsao, MD, FRCPC Department of Pathology, Princess Margaret Hospital Division of Cellular and Molecular Biology, Ontario Cancer Institute University of Toronto Objective: To report the results of 2 important clinical trials reported at 2004 American Society of Clinical Oncologist Main message: Molecular Pathology will soon be an important component of pathological diagnosis in lung cancer Benefit primarily for stage II patients Summary on adjuvant chemotherapy The results of BR.10 study together with results of other recent adjuvant chemotherapy studies (IALT, UFT, CALGB 9633) will likely change the standard of treatment for early stage (I and II) non-small cell lung cancer patients. ras mutation may further define subgroup of patients who would benefit from adjuvant chemotherapy. In the future, it will not be adequate for a pathologist to make only histopathological diagnosis without additional molecular analysis for lung cancer patients. Future molecular studies to be performed on BR.10 tumor samples Additional mutational analyses: p53, p16 Microarray studies: mRNA expression profiling genomic DNA copy number changes Additional genes previously identified as potential prognostic markers by other investigators Small molecule EGFR inhibitors BR.21 Study Design - 2 BR.21 Study Endpoints Primary Overall survival Secondary Quality of life Progression-free survival Response rate duration of response Toxicity tolerability BR.21 Results 731 patients randomized Aug/01 – Jan/03 22 ineligible 2 regimens (9) Only single agent in young patient (2) CT or RT given within 2-4 weeks, concurrent CT (5) Biochemical abnormalities (4) Symptomatic CNS metastases (2) BR.21 Patient Characteristics BR.21 Progression Free Survival BR.21 Overall Survival BR.21 Summary This is the first placebo controlled randomized trial to confirm that an oral tyrosine（酪氨酸） kinase inhibitor of EGFR can prolong survival Treatment with erlot