Abstract 503P
Background
Most retrospective data suggest that UPTR confers a survival benefit in patients with unresectable synchronous asymptomatic mCRC. The possible mechanisms that could explain the different outcomes based on UPTR or not are not known.
Methods
We retrospectively analyzed the mutational landscape (excluding Variants of Unknown Significance) in 64 consecutive patients with synchronous mCRC who underwent a comprehensive genomic profiling with the Guardant360 74 gene panel at baseline and at first tumor progression according to UPTR in the context of tumour location and RAS status. The Variant Allele Fraction (VAF%) and the total number of new alterations at first progression were evaluated.
Results
1- The total number of new alterations at first progression was higher in all subgroups for the non UPTR patients (Table): Table: 503P
| Left side + Rectum wild type | Left side + Rectum mutant | Right side mutant | |
| New alterations at first progression | |||
| UPTR | N: 4 BRAF amp, CDK12 D643fs, FGFR1 amp, PIK3CA amp. | N: 1 RB1 R621H | N: 2 APC L292FS, TP53 P177L |
| NO UPTR | N: 7 APC R405,CDKN2A H83Y, PIK3CA E545K, TP53 R273H, APC splice site SNV, NOTCH1 V1721fs, PTEN P2045 | N: 11 APC L749fs, KRASG12D, NOTCH1 S1708, TP53 S240G, TP53 V274G, TP53 E336FS, EFGR amp, MAP2K1 K57N, NRASG12V, TP53 E336, TP53 E271V | N: 13 APC R1450, EGFR amp, HNF1A R203H, PIK3CA E545K, STK11 P281L, TP53 R175H, TP53 R273C, BRAF amp, FGFR1 amp, PIK3CA E542K, PTEN F257S, TP53 C275W, TP53 R273H |
The median number of metastatic sites at baseline was the same between both subgroups although more irresectable metastatic sites were found in the non UPTR subgroup 2- For Left side + rectum locations either wild-type or mutant, the median VAF% was higher at baseline and at first progression in patients without UPTR as compared with UPTR. This was not the case in the right-side mutant subgroup: Left side + Rectum WT median VAF%: Baseline: no UPTR vs UPTR: 51.1% vs 22.5%. At first progression: 23.3% vs 9.0%. Left side + Rectum mutant median VAF%: Baseline: no UPTR vs UPTR: 90.5% vs 49.0%. At first progression: 68.7% vs 64.9% Right side mutant median VAF%: Baseline: no UPTR vs UPTR: 58.4% vs 107.9%. At first progression: 39.76% vs 67.3%
Conclusions
Clearly higher number of new molecular alterations at first tumoral progression were detected in patients with synchronous mCRC and no UPTR as compared with those patients with UPTR. Next-Generation Sequencing platforms may be of great value to clarify different outcomes of mCRC patients and to further validate our findings in larger prospective studies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain.
Funding
Guardant Health providing the samples.
Disclosure
M. Benavides: Financial Interests, Personal, Advisory Board, Advisory: Amgen; MSD; Sanofi; BMS; Merck; Non-Financial Interests, Other, Samples provider: Guardant Health. J. Alcaide-Garcia: Financial Interests, Personal, Invited Speaker: Amgen. C. Reyna: Financial Interests, Personal, Advisory Board: Servier; Sanofi; Roche; Merck; Lilly. M. Alvarez: Financial Interests, Personal, Advisory Board: Bristol; Financial Interests, Personal, Invited Speaker: Novartis; Roche; Nanostring. M. Kushnir: Financial Interests, Personal, Full or part-time Employment: Guardant Health. I. Faull: Financial Interests, Personal, Stocks/Shares: Guardant Health; Financial Interests, Personal, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.