Abstract 455P
Background
Tumor-tissue biopsy is the standard of care (SOC) to assess RAS & BRAF ms in mCRC pts. However, the analysis of circulating cfDNA has the advantage of evidencing genetic tumor heterogeneity. We explored the occurrence of KRAS, NRAS and BRAF sequence variants (sv) using cfDNA in 1L SOC RAS wt mCRC pts. The concordance of RAS ms between tissue and cfDNA, and the association of cfDNA RAS ms and ORR were also explored.
Methods
Prospective, observational, multi-center study in mCRC pts with baseline RASwt according to tissue biopsy and treated following clinical practice. Plasma samples were collected before 1L treatment and centrally analyzed in all pts using the Idylla™ test (Biocartis). The baseline plasma of 20 pts were also analyzed using the BEAMing technique (Sysmex). RECIST tumor response was evaluated approx every 3 months.
Results
114 pts were evaluable (68% male; median age: 65 y). 106 received chemotherapy (CT) + anti-EGFR (101 panitumumab), 3 CT + anti-VEGF and 5 CT alone. Six (5.3%) & 5 (4.4%) pts showed RAS & BRAF V600 sv in cfDNA, respectively. At baseline, the % of RAS ms concordance between tissue and cfDNA (Idylla) was 94.7, and between the two cfDNA assays was 90.0 ORR was 75.9% (95%CI: 66.8-83.6) for all pts and 80.2% (95%CI: 70.8-87.6) in the panitumumab subgroup. In this subgroup, 80% presented left-sided (LS) tumors and 19% right-sided (RS) (1% both sides). Table shows the association between baseline RAS & BRAF ms and ORR by tumor site in the panitumumab subgroup. Table: 455P
| Panitumumab subgroup, % (95%CI) | wt (Idylla) | mt (Idylla) | Total ( RAS wt tissue) |
| RAS | n = 90 | n = 6 | n = 96 |
| ORR | 81.1 (71.5 - 88.6) | 66.7 (22.3 - 95.7) | 80.2 (70.8 - 87.6) |
| Odds | 2.15 (0.36 - 12.70) | ||
| Left side | n = 74 | n = 3 | n = 77 |
| ORR | 86.5 (76.6 - 93.3) | 66.7 (9.4 - 99.2) | 85.7 (75.9 - 92.7) |
| Odds | 3.20 (0.26 - 38.64) | ||
| Right side | n = 17 | n = 3 | n = 20 |
| ORR | 58.8 (32.9 - 81.6) | 66.7 (9.4 - 99.2) | 60.0 (36.1 - 80.9) |
| Odds | 0.71 (0.05 - 9.50) | ||
| BRAF | n = 89 | n = 3 | n = 92 |
| ORR | 82.0 (72.5 - 89.4) | 66.7 (9.4 - 99.2) | 81.5 (72.1 - 88.9) |
| Odds | 2.28 (0.19 - 26.72) | ||
| Left side | n = 74 | n = 1 | n = 75 |
| ORR | 87.8 (78.2 - 94.3) | 0 (0 – 97.5) | 86.7 (76.8 - 93.4) |
| Odds | - | ||
| Right side | n = 16 | n = 2 | n = 18 |
| ORR | 56.3 (29.9 - 80.3) | 100 (15.8 - 100) | 61.1 (35.8 - 82.7) |
| Odds | - |
Odds ratio: wt vs mt (Idylla). One patient had right + left tumor location
Conclusions
The RAS ms concordance between baseline tissue and Idylla cfDNA was 94.7%. ORR in CT + panitumumab treated RAS wt (by baseline tissue biopsy) pts was high, and tended to be higher in LS tumors and/or baseline cfDNA (by Idylla) RAS wt. % of cfDNA RAS and/or BRAF sv tends to be higher in RS tumors. Further investigation in larger numbers of pts is warranted Study supported by Amgen.
Clinical trial identification
NCT02792478.
Editorial acknowledgement
Legal entity responsible for the study
Amgen S.A.
Funding
Amgen S.A.
Disclosure
M. Valladares-Ayerbes: Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Other, Personal fees: Amgen, Bayer, Celgene, Merck, Sanofi, Servier, Roche. M.J. Safont: Financial Interests, Personal, Funding, Congress/course assistance: Roche, Amgen, Merck, Sanofi; Financial Interests, Personal, Invited Speaker, Speaker or advisory role: Amgen, Bayer, BMS, Merck, MSD, Pierre Fabre, Roche, Sanofi, Servier. E. González-Flores: Financial Interests, Personal, Advisory Board, Advisory board and lectures: Amgen. P. García-Alfonso: Financial Interests, Personal, Advisory Role, Speaker, consultancy or advisory roles: Amgen, Bayer, Bristol, Merck Serono, MSD, Lilly, Roche, Sanofi, Servier, Pierre Fabre. E. Aranda Aguilar: Financial Interests, Personal, Advisory Role: Amgen, Bayer, Celgene, Merck, Roche, Sanofi. J. Aparicio: Financial Interests, Personal, Advisory Role: Amgen, Merck, Sanofi, Servier, Bayer, Pierre Fabre. J.J. Cruz-Hernández: Financial Interests, Personal, Invited Speaker: Merck, BMS, MSD, Roche, AstraZeneca, Novartis; Financial Interests, Personal, Advisory Role: Merck, MSD, BMS, Novartis. M. Salgado Fernández: Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Amgen. R. Garcia-Carbonero: Financial Interests, Personal, Other, Scientific Advice, Speakers Bureau, Honoraria: AAA, Advanz Pharma, Bayer, BMS, HMP, Ipsen, Merck, Midatech Pharma, MSD, Novartis, PharmaMar, Pfizer, Pierre Fabre, Roche, Sanofi and Servier; Financial Interests, Personal, Principal Investigator, Financial supp to IIT evaluating Axitinib (NETs), Nivolumab (NECs) and Pembrolizumab-Olaparib (CRC): Pfizer, BMS, MSD; Financial Interests, Institutional, Research Grant, Institutional support for the conduct of clinical trials or for molecular diagnostic platforms: ARMO Biosciences, AstraZeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics, Boston Biomedicals, Merck, MSD, Amgen, Sanofi, Bayer, Bristol-Myers-Squibb, Boerhringer, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, Pharmamar; Non-Financial Interests, Personal, Member of the Board of Directors: Spanish Neuroendocrine Tumor Cooperative Group (GETNE), European Society of Neuroendocrine Tumors (ENETS); Non-Financial Interests, Personal, Principal Investigator, Global PI of CTs: Axitinib (Pfizer) in NETs; Nivolumab (BMS) in NECs; Pembrolizumab-Olaparib in CRC: Pfizer, BMS; Non-Financial Interests, Personal, Member: EORTC, ASCO, ESMO, SEOM, TTD, GEMCAD. B. Massuti Sureda: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Merck Serono, Pfizer, Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Roche. A. Lloansi Vila: Financial Interests, Personal, Full or part-time Employment: Amgen; Financial Interests, Personal, Stocks/Shares: Amgen. All other authors have declared no conflicts of interest.