How I utilize mutational analysis in NSCLC - Imedex：我如何利用突变分析NSCLC - imedex.ppt

PFS Common Mutants (Del 19/L858R) Yang et al. ASCO 2012 Abstract LBA7500 QOL: EORTC QLQ C-30 Yang et al. ASCO 2012 Abstract LBA7500 Summary LUNG LUX-3 Front-line afatinib improved QOL, RR, DCR, and median PFS over cisplatin-pemetrexed in both the overall EGFR mutation population and in the common EGFR mutation (del19/L858) patients. Subgroup analysis showed benefit across most of the subgroups. No new safety signals with diarrhea and rash as the most frequent AEs. On July 12, 2013, the FDA approved afatinib for front-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 (L858R) as detected by an FDA-approved test. Yang et al. ASCO 2012 Abstract LBA7500 Front-line EGFR TKI EGFR TKI monotherapy in NSCLC patients with sensitive EGFR mutations improves PFS over chemotherapy. However, EGFR TKI monotherapy should not be given to patients without EGFR mutations, i.e. EGFR wild-type (WT). EGFR WT patients need front-line chemotherapy. It is unclear which EGFR TKI should be used front-line. It is unclear whether EGFR TKI + chemo or chemo then maintenance erlotinib would improve survival for EGFR mutation patients. CALGB 30406 frontline study (ASCO 2010) FAST - ACT (intercalating EGFR TKI with chemo) – await results. There are concerns over combining erlotinib-chemo as erlotinib arrests the cancer cells in the G1 checkpoint and chemo usually works best in the mitotic phase. SATURN – showed that EGFR mutation patients had significant survival improvement with maintenance erlotinib after 4 cycles of chemo. Background Epidemiology Histology Molecular Profiling Outline: NSCLC EGFR mutants IPASS EURTAC LUX LUNG 3 EML 4 ALK, ROS 1 Crizotinib Upcoming agents ALK – anaplastic lymphoma kinase EML 4 – echinoderm microtubule associated protein like 4 Found Primarily in adenocarcinoma patients who are never- or light former smokers, EGFR and KRAS WT, and younger All adenocarcinomas: 9% EML4-ALK If EGFR WT, Caucasian never-smoker, adenocarcino