Abstract 922P
Background
Detecting KRAS mutations in tumor samples can be challenging in low-middle-income countries due to limited access to molecular biology laboratories. The Idylla TM KRAS mutation test (IKMT) is an IVD, automated, and rapid qPCR assay to detect KRAS mutations, validated in colorectal cancer. We studied the concordance of the IKMT in KRAS mutation detection, compared with NGS, and performed a prospective KRAS mutation test feasibility study in samples from patients with NSCLC.
Methods
To study the concordance of IKMT to NGS we included lung cancer samples sequenced using the Oncomine Focus Assay (OFA) NGS panel. The positive percentage agreement (PPA) and negative percentage agreements (NPA) were estimated. To study the feasibility of KRAS testing using IKMT we prospectively included patients with stage IV lung cancer with wild-type EGFR, BRAF, ALK, and ROS1 tumors. The Idylla KRAS mutation test was performed according to manufacturer instructions in an Idylla TM platform (Biocartis) in 2 hours.
Results
To study the concordance between IKMT and NGS, 26 KRAS mut and 20 KRAS wt samples were included. The concordance rate was 100% and PPA was 100% in 25 KRAS mutant samples: G12C (N =12), G12V (N = 7), Q61H (N = 3), G12A (N = 1), G12D (N = 1) and G12S (N= 1). The NPA was 100%. In the feasibility study, 135 patients were included, IKMT was successfully done in 131 (97%) samples, two did not meet assay quality control, and two runs were aborted by the system due to cartridge issues. The median tumor cell percentage in the sample was 65% (range: 10-95), median tumor area in tissue slides was 23 mm2 (range:5-500). Among the 131 samples tested, 54 (41%) had a detectable KRAS mutations, including G12C (N = 23, 17.6%), G12V (N =15, 11.5%), G12A (N = 5, 3,8%), G12D (N = 3, 2.3%), G13D (N = 3, 2.3%), G12S (N = 2, 1.5%), Q61H (N =2, 1.5%) and A146P/T/V (N = 1, 0.8%). The rate of KRAS mutation detection was similar across sample size (39.3% in < 25mm2 vs.38.2% in >25mm2, p = 0.9) and biopsy procedure (surgical 45.6% vs.core/FNA 30.9%, p = 0.13).
Conclusions
The Idylla TM KRAS mutation test shows high concordance and agreement with NGS testing to detect KRAS mutations in lung cancer samples. KRAS G12C mutations were found in about 18% of tumors without EGFR, BRAF, ALK, and ROS1 alterations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Amgen.
Disclosure
G. Recondo: Financial Interests, Advisory Board: Amgen, Bayer, Biocartis, BMS, Merck Serono, MSD, Pfizer, Roche, Takeda; Financial Interests, Research Grant: Amgen, Janssen. M.V. Bluthgen: Financial Interests, Invited Speaker: Roche, MSD, BMS, AstraZeneca, Pfizer, Takeda. A. Perfetti: Financial Interests, Advisory Board: Roche, Pfizer, Boehringer, BMS, MSD, Amgen, Novartis, Boehringer Ingelheim. N. Castagneris: Financial Interests, Invited Speaker: Takeda, BMS, Amgen, Roche, Pfizer, AstraZeneca. L. Lupinacci: Financial Interests, Advisory Board: BMS, Amgen, Roche, Pfizer. J.N. Minatta: Financial Interests, Research Grant: Pfizer; Financial Interests, Advisory Board: Pfizer, MSD, Takeda, Roche, Raffo, Merck, Amgen. All other authors have declared no conflicts of interest.