Abstract 3887
Background
Tumour-tissue biopsy testing is the standard of care (SOC) to assess RAS mutation in mCRC pts. However, the analysis of circulating cell-free DNA (cfDNA) has the added advantage of being able to evidence genetic tumour heterogeneity. We explored the correlation of the RAS mutational status assessed in plasma samples with first-line (1L) treatment outcomes in SOC RAS wild type (wt) mCRC pts.
Methods
Prospective, observational, multi-centre study in mCRC pts with RASwt according to tumour-tissue biopsy and treated following standard clinical practice. Plasma samples were collected before starting 1L treatment and sent to Sysmex Inostics GmbH for BEAMing analysis. The lower threshold limit was a mutant allele fraction (MAF) ≥ 0.02%. Tumour response (TR) was evaluated approximately every 3 months based on RECIST criteria.
Results
119 pts were included (61% male; median age: 65 y). 113 received chemotherapy (CT) + anti-EGFR, 4 CT + anti-VEGF and 2 CT alone. Overall response rate (ORR) was 68.1% (95%CI: 58.9-76.3) for all pts and 75% (95%CI: 65.8-82.8) in the108 pts with TR data. In pts treated with panitumumab (n = 92), the most homogeneous group, 76.1% (n = 70) presented left-sided tumours and 19.6% (n = 18) right-sided; overall ORR was 78.3% (95%CI: 68.4-86.2); 81.4% (95%CI: 70.3-89.7) for left and 72.2% (95%CI: 46.5-90.3) for right-sided pts. ORR in the panitumumab subgroup according to RAS mutational status analysed in cfDNA for the three MAF (cut-offs) considered is presented in the table.Table: 546P
| ORR (not confirmed) % (95% CI) | ORR (not confirmed) % (95% CI) | Odds Ratio (95% CI); P-value* | |
|---|---|---|---|
| Mutant allele fraction, cut-off (n) | RASwt | RASmt | |
| ≥1% (90 wt/2 mt) | 78.9 (69.0 – 86.8) | 50.0 (1.3 - 98.7) | 3.7 (0.2 – 62.6) 0.389 |
| ≥0.1% (87 wt/5 mt) | 79.3 (69.3 – 87.3) | 60.0 (14.7 - 94.7) | 2.6 (0.4 – 16.5) 0.297 |
| ≥0.02% (80 wt/12 mt) | 80.0 (69.6- 88.1) | 66.7 (34.9-90.1) | 2.0 (0.5 – 7.5) 0.285 |
Fisher Test; CI=confidence interval; ORR: Overall Response Rate.
Conclusions
A high ORR was observed in pts treated with panitumumab independently of the localization. ORR in panitumumab treated patients tends to be higher in plasma RASwt. ORR in pts with plasma RASmt increases when a lower MAF cut-off is used. Further investigation is needed to find the optimal clinical cut-off. Study supported by Amgen.
Clinical trial identification
Legal entity responsible for the study
Amgen.
Funding
Amgen.
Editorial Acknowledgement
Disclosure
P. García Alfonso: Consulting fees: Amgen, Bristol, Merck, Sanofi, Roche, Bayer, Servier. M. Valladares-Ayerbes: Research grants: Roche; Consulting fees: Amgen, Roche, Merck, Sanofi, Servier. J.M. Viéitez: Research grants: Amgen, Roche; Consulting fees: Amgen, Roche, Servier, Shire, Bayer. J.J. Cruz Hernandez: Consulting fees: Amgen, Merck, Roche, BMS. A. Lloansí Vila: Full time employee, stocks: Amgen. All other authors have declared no conflicts of interest.
Resources from the same session
1159 - Molecular characterization and search for founding effects in Canarian families with Hereditary Breast and Ovarian Cancer Syndrome
Presenter: Elisenda Llabres Valenti
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3725 - Effect of the polymorphism rs2066844 of the NOD2 gene on colon cancer incidence in a high cardiovascular risk population. Modulation by gender
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
3708 - Effect of the polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a high cardiovascular risk population
Presenter: Judith Begona Ramirez Sabio
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5057 - Association of a genetic variant in cyclin-dependent kinase Inhibitor 2A gene with the increased risk of breast cancer
Presenter: Soodabeh Shahid Sales
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5970 - Investigating the role of HAT protein TIP60 in regulating functional dynamics of nuclear receptor PXR
Presenter: KARISHMA BAKSHI
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1360 - The role of downregulated SIRT3 expression in patients with hepatocellular carcinoma
Presenter: Hanhee Jo
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1634 - Prediction and Intervention of Colorectal Cancer Risk with Artificial Intelligent System
Presenter: Yang Ge
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
4921 - Measuring the Efficiency of Cancer Care in Europe
Presenter: Rikard Althin
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
1235 - Circulating cell-free DNA isolated from plasma of mesenteric veins predicts prognosis in stage II colorectal cancer patients
Presenter: Chih-Yung Yang
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract
5169 - _lonality of uterine carcinosarcoma as a factor of clinical prognosis.
Presenter: Natalia Levitskaya
Session: Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Resources:
Abstract