Epidermal growth factor receptor (EGFR) genotyping of matched urine, plasma and tumor tissue from non-small cell lung cancer (NSCLC) patients (pts) treated with rociletinib.

Abstract

9001 Background: Rociletinib is an oral inhibitor of mutant EGFR, including T790M. We compared EGFR mutation detection in circulating tumor DNA from blood and urine to that in matched tissue in TIGER-X (NCT01526928), a phase 1/2 study of rociletinib in pts with mutant EGFRpositive advanced NSCLC. Methods: EGFR status was assessed by the therascreen EGFR test (Qiagen) in tissue, BEAMing (Sysmex) in plasma, and a quantitative short footprint assay method that uses next-generation sequencing (Trovagene) in urine. Results: Of 417 pts in the 500 and 625 mg BID dosing groups (data cut-off date: 18 Sept 2015; pts enrolled as of 1 July 2015), 331 of 417 were T790M+ by central tissue genotyping; 189 of 242 were T790M+ by plasma genotyping; and 136 of 169 were T790M+ by urine genotyping. Confirmed investigator-assessed objective response rate (ORR) and median duration of response (mDOR) were similar regardless of sample type (Table). Four of 14 pts who were T790M+ in plasma but T790M− in tissue responded; 3 of 7 pts who were T790M+ in urine but T790M− in tissue responded. Shrinkage of target lesions correlated with higher T790M:activating mutation ratio in plasma (P=0.006). With tissue as reference, positive percent agreement for T790M status between matched plasma and tissue was 81.5% (n=195) and 83.8% (n=136) between matched urine and tissue. In both dosing groups, the most common treatment-related adverse events were hyperglycemia, diarrhea, nausea, and fatigue. Conclusions: In T790M+ pts, response was similar whether T790M status was identified by tissue, plasma or urine. Plasma and urine testing identified T790M mutations missed by biopsy due to tumor heterogeneity or inadequate sample quality. These data suggest plasma and urine EGFRanalyses complement tissue biopsies in EGFR TKI resistant NSCLC. Clinical trial information: NCT01526928. 500 mg BID 625 mg BID Tissue Plasma Urine Tissue Plasma Urine n (T790M+) 156 61 50 175 128 86 ORR, % 25.0 27.9 32.0 39.4 33.6 40.7 95% CI 18.4-32.6 17.1-40.8 19.5-46.7 32.1-47.1 25.5-42.5 30.2-51.8 mDOR, mo 9.0 9.0 9.0 7.9 6.7 8.0 95% CI 4.6-11.0 4.4-11.0 2.6-11.0 5.6-9.2 4.8-9.0 6.8-11.2 CI, confidence interval; mo, months; NR, not reached.