Abstract 461P
Background
Young-onset colorectal cancer (YOCR) is defined as diagnosis below the age of 50. The incidence of YOCRC is increasing at an alarming rate, but causes and pathogenesis remain unknown and YOCRC is not well characterized. We aimed to characterize the molecular characteristics of YOCRC in patients (pts) diagnosed at our centre and to evaluate the impact of molecular tumor profiling (MTP) in ameliorating the current development in metastatic YOCR.
Methods
Pts with a diagnosis of metastatic YOCR visited for the first time at Vall d’Hebron University Hospital between January 2017 and October 2020 were included in the analysis. Data of MTP including alterations (mt) detected by VHIO-Card Amplicon panel and VHIO-Card-300-v3 panel and data concerning enrollment in phase I trials using molecular targeted agents (MTAs) were collected. Benefit was calculated comparing treatment failure of prior line (TTF1) to the MTAs’ one (TTF2). TTF2/TTF1≥1.3 supposed MTAs benefit.
Results
177 pts presented metastatic YOCR of whom 105 patients had data of MTP. MTP status was: MSI-H: 2 (6%), P53mt 83 (79%), APCmt 61 (58%), KRASmt: 53 (50%), NRASmt: 4 (4%), BRAFmt: 5 (5%), PIK3CAmt: 16 (15%), RNF43mt: 4 (4%), FBXW7mt: 3 (3%), BRCA1mt: 3 (3%), NOTCH1mt: 2 (2%), CTNNB1mt: 1 (1%), ATMmt: 1 (1%). No Her2 alterations were observed. 33 pts (18.6%) were included in phase I trials (PhIT) testing BRAF inh (1), Wnt inh (3), VEGF inh (1), anti-tubulin agents (5), MET inh (1), antiEGFR (1), immunotherapy-based treatment (IT) (18) and others (3). Median of previous lines before inclusion in PhIT: 2 (1-5). Median (m)TTF1 was 28.3 weeks (w) (1.4w-105w), mTTF2 9.7w (2.1w-234w). 6 pts (18.2%) presented a TTF2/TTF1 ratio ≥1.3, of which 5 received IT. In 5 pts (15.2%), treatment was selected based on actionable molecular alterations (RAS/BRAF wt and MSI status), 3 presenting benefit.
Conclusions
YOCR does not present particular molecular alterations in our cohort in current screening programs (SP) and do not differ from historical data in overall mCRC population, hindering enrollment in PhIT using matched MTA. Specific SP for YOCR should be developed. Significant benefit is observed for YOCR included in PhIT treated with IT and intrinsic mechanisms should be further investigated.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I. Baraibar Argota: Financial Interests, Personal, Invited Speaker: Sanofi. J. Ros: Financial Interests, Personal, Invited Speaker: Sanofi. J. Capdevila: Financial Interests, Personal, Invited Speaker: Scientific consultancy role (speaker and advisory roles) from Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, ITM, Sirlex and Merck Serono. Research grants from Novartis, Pfizer, AstraZeneca, Advanced Acc. E. Garralda: Financial Interests, Other: Consulting or Advisory Role: Roche, Ellipses Pharma, Neomed Therapeutics, Janssen, Boehringer Ingelheim, Seattle Genetics, TFS, Alkermes, Thermo Fisher Scientific, Bristol-Myers Squibb; Speakers’ Bureau: MSD, Roche, Thermo Fisher Scientific Research Funding. P. Nuciforo: Financial Interests, Personal, Invited Speaker: Honoraria: Bayer, Novartis, MSD Oncology, MSD Oncology Consulting or Advisory Role: Bayer, MSD Oncology Travel, Accommodations, Expenses: Novartis. R. Dienstmann: Financial Interests, Personal, Invited Speaker: Consulting or Advisory Role: Roche Speakers’ Bureau: Roche, Ipsen, Sanofi, MSD Oncology, Servier, Amgen Research Funding: Merck. A. Vivancos: Financial Interests, Invited Speaker: Consulting or Advisory Role: Guardant Health, Novartis, Bayer Health. J. Tabernero: Financial Interests, Personal and Institutional, Other: Josep Tabernero reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limi. M.E. Elez Fernandez: Financial Interests, Personal, Invited Speaker: Consulting or Advisory Role: Amgen, Roche, Merck Serono, Sanofi, Servier, Bayer, Pierre Fabre Research Funding: Merck Serono, Sanofi/Aventis (Inst) Travel, Accommodations, Expenses: Roche, Merck Serono, Sanofi, Amgen. All other authors have declared no conflicts of interest.