Abstract 427P
Background
Tumor tissue comprehensive genomic profiling (CGP) identifies molecular targets for precision oncology but with turnaround time (TAT) around one month. We conducted tumor tissue CGP for advanced stage cancer pts from AME using a new and potentially faster tissue-based NGS platform.
Methods
Using DNA-based hybrid capture technology, Guardant360 TissueNext™ reports point mutations and insertions/deletions in 84 genes, fusions for 13 activating partners, amplification (amp) of 20 genes, tumor mutation burden (TMB) score, and microsatellite instability (MSI) status.
Results
Tumor tissue from 412 pts was tested, with success rate 87.3%. Median pt age was 61 years; 54% were male. Median TAT was 15 days (range, 6-127). Mean alteration count/sample was 3.1 (range, 1-29) and mean variant allelic frequency was 19.4% (range, 1.7-88.3). The most profiled cancers included lung (49.4%), colon or rectum (CRC; 9.0%) and breast (6.0%). TP53 (64.6%), EGFR (26.9%) and KRAS (19.0%) were the most mutated genes. EGFR (18.4%), FGFR1 (6.6%) and CCNE1 (6.6%) were the most frequently amplified genes. Fusions were identified in 30 (8.2%) pts and included ALK (2.7%), ROS1 (1.4%) and RET (1.4%). MSI-high was reported for 1.1% and TMB ≥10 mutations/Mb was found in 11.7%. For non-small cell lung cancer (n=176), alterations in genes recommended for testing by the National Comprehensive Cancer Network were mutations in EGFR (53.4%), KRAS (11.5%; 4.3% G12C), ERBB2 (3.7%) and BRAF V600E (1.4%); fusions of ALK (5.5%), ROS1 (2%), RET (2%) and NTRK1/3 (1.7% combined); MET exon14 skipping (1.7%) and MET amp (5.6%). MSI-high and TMB≥10 mutations/Mb were found in 0.7% and 12%, respectively. For CRC (n=33), informative alterations included KRAS mutations (45.4%), BRAF V600E (3%), and ERBB2 amp (6%); 1 patient each had RET and NTRK1 fusions. In breast cancer (n=22), relevant alterations included ERBB2 amp (22%) and mutations in PIK3CA (43%), ESR1 (4.8%), ERBB2 (4.8%) and BRCA1/2 (4.8%).
Conclusions
This analysis of the first tumor samples tested by a new CGP panel in AME demonstrated detection of actionable alterations at the expected frequency with only 15 days median TAT.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Sandhir, S. Olsen: Financial Interests, Personal, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.
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