Abstract 521P
Background
Comprehensive genomic profiling (CGP) of tumor tissue (Tx) identifies precision oncology targets but typically requires tumor content (TC) of at least 20% and has a one-month turnaround time (TAT). We retrospectively evaluated the results of a new Tx-based CGP assay designed to overcome these hurdles.
Methods
NGS analyzed Tx samples from advanced cancer patients (pts) in AME at a central laboratory in United States (US). Using DNA-based hybrid capture technology, Guardant360 TissueNext™ v1.0 reports point mutations (mts), insertions (ins)/deletions, amplification (amp, and fusions (fus) in up to 84 genes, plus tumor mutation burden (TMB) and microsatellite instability (MSI) status. Frequencies of alterations (alts) detected in this cohort were compared to other publicly available databases from US and China using cBioPortal.
Results
We processed 1160 samples from 954 pts (49% women, median age 61 years). Most patients had lung adenocarcinoma (LuAd, 41%), followed by colorectal cancer (11%) and breast cancer (9%). Assay success rate was 83.8%. Median TAT was 13 days (5-83 days). Most mutated genes were TP53 (64%), EGFR (24%), and KRAS (19%). Common amps were EGFR (16%), MYC (7%), and FGFR1 (6%), and fus included ALK (3%), FGFR (1%), and RET (1%). 1% of pts had MSI-high, and 12% had TMB-high (³10 mt/Mb). 17% pts had TC ≤10%. Detection rates for EGFR mts, MET amp, and ALK fus were 25%, 4%, and 3% for TC ≤10% versus 24%, 4%, and 3%, respectively, for TC >10%. Among the largest subset, LuAd pts, actionable alts included EGFR (56%), KRAS (14%; 5% G12C), and ERBB2 (5%) mt; BRAF V600E (1%); ALK (5%), RET (2%), NTRK1 (0.6%) and ROS1 (2%) fus; MET amp (5%) and exon 14 skipping (1%); MSI-H (1%) and TMB-high (13%). Uncommon EGFR mts were seen in 16% of pts. 35% of EGFR exon 20 ins were outside of known hotspots. Rare fus in EGFR, MET, BRAF, and FGFR genes were observed in 2.6% of samples combined. For LuAd samples, database comparison revealed consistent detection rates with China and US except for EGFR (lower in US) and KRAS (higher in US).
Conclusions
Our analysis revealed that this CGP assay can detect actionable and rare alterations with expected frequency with a median TAT of 13 days. Biomarker detection was feasible even when TC<20%.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Guardant Health AMEA, Singapore, 138567.
Funding
Guardant Health AMEA, Singapore, 138567.
Disclosure
N. Rohatgi, A. Bahl: Financial Interests, Personal, Advisory Board: Guardant Health-AMEA. S. Dawood: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Lilly, Merck, Gilead; Financial Interests, Personal, Invited Speaker: Roche, MSD, BMS, Pfizer, Lilly, AstraZeneca, Caris; Financial Interests, Institutional, Research Grant: MSD, Amgen; Non-Financial Interests, Personal, Member: ASCO, ESMO. A. Kaur, N. Sandhir, S. Olsen: Financial Interests, Personal, Full or part-time Employment: Guardant Health-AMEA. All other authors have declared no conflicts of interest.