EML4-ALK in NSCLC: The OSU Experience.

Abstract

e18014 Background: EML4-ALK gene translocation is a novel carcinogenic change described in NSCLC in 2007. Prior studies report this translocation in 1-11% of screened patients (pts) and an association with never/light smoking, male sex, absence of EGFR or KRAS mutations, and adenocarcinoma histology. Compared to other NSCLC pts, ALK positive pts have similar responses to platinum chemotherapy, resistance to erlotinib, and no difference in OS. 82 ALK positive NSCLC pts were treated on a phase I trial of crizotinib (ALK inhibitor) with an ORR of 57% with 46 PRs and 1 CR. Phase II/III trials of crizotinib in selected pts are ongoing. We report the experience with EML4-ALK translocation NSCLC pts at the Ohio State University Comprehensive Cancer Center. Methods: ALK translocation screening was performed using FISH on pts with adenocarcinoma or light/never smokers, who were EGFR/KRAS mutation negative. FISH analysis was performed with LSI ALK dual color break-apart probe; a positive result was 10% or more tumor cells splitting ALK-ba signals. IHC using clone 4A5 and Clone SP8 was also used to detect ALK protein expression in 19 pts. Results: Over 12 months, 283 NSCLC pts were screened for EGFR and KRAS. 202 pts were negative for both and were screened for ALK. 30 pts (14.9%) were positive (18 men, 12 women) with a median age of 59. Most pts were never or light smokers (14 never, 5 light). Adenocarcinoma was the most common histology (22 pts); however 5 pts had adenosquamous, 2 had squamous, and 1 had small cell histology. Average survival was 25.4 months; 5 patients survived 5+ years (65-85 months). 24 pts received platinum-based chemotherapy, 11 received erlotinib, and 18 received pemetrexed. Three pts had prolonged response to single agent pemetrexed (11- 36 cycles) and 1 pt had prolonged response to weekly paclitaxel (37 cycles). Conclusions: EML4-ALK is emerging as an important target for a subpopulation of lung cancer pts. Our single institution experience raises several important questions. The results warrant further considerationof screening all adenocarcinoma variants including adenosquamous, and the activity of pemetrexed in this population. The finding of ALK translocation in a small cell pt is intriguing. ALK testing with IHC is an ongoing area of study.